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Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD).,We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS).,Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction.,Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D.,Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.,Of 1210 patients, 1167 had data available for GOLD classification.,Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted.,Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group.,The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.,Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline.,Net treatment benefit was similar in patients with low or high levels of symptoms.,ATTAIN (ClinicalTrials.gov identifier: NCT01001494) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397).,The online version of this article (doi:10.1186/s12931-016-0372-1) contains supplementary material, which is available to authorized users. | Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy.,GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.,In this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices).,The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12.,Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min-4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.,A total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study.,On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46-101 mL) and 64 mL (95% CI 28-99 mL), respectively (both P<0.001).,IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min-4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01).,TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05).,The incidence of adverse events was similar for the two treatment groups.,In patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes. | 1 |
Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover.,Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases.,We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.,We assessed the expression of WNT-pathway genes and the functional role of β-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD.,Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling.,Stimulation of fibroblasts with TGF-β1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and β-catenin mRNA expression.,The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-β1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar.,Accordingly, TGF-β1 activated β-catenin signaling, as shown by an increase in transcriptionally active and total β-catenin protein expression.,Furthermore, TGF-β1 induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by β-catenin specific siRNA and by pharmacological inhibition of β-catenin, whereas the TGF-β1-induced expression of PAI-1 was not affected.,The induction of transcriptionally active β-catenin and subsequent fibronectin deposition induced by TGF-β1 were enhanced in pulmonary fibroblasts from individuals with COPD.,β-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation.,WNT/β-catenin pathway expression and activation by TGF-β1 is enhanced in pulmonary fibroblasts from individuals with COPD.,This suggests an important role of the WNT/β-catenin pathway in regulating fibroblast phenotype and function in COPD. | 1 |
To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets.,The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus.,After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs).,The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID).,The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA.,Furthermore, we constructed a protein-protein interaction (PPI) network for DEGs.,The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively.,A total of 39 up- and 15 downregulated DEGs were screened.,Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process.,Moreover, we also found that HLA-A has the highest degree in the PPI network.,The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05).,Our results may help further the understanding of the mechanisms of COPD.,The identified DEGs, especially HLA-A, may serve as diagnosis markers for COPD. | Despite the status of chronic obstructive pulmonary disease (COPD) as a major global health problem, no currently available therapies can limit COPD progression.,Therefore, an urgent need exists for the development of new and effective treatments for COPD.,An improved understanding in the molecular pathogenesis of COPD can potentially identify molecular targets to facilitate the development of new therapeutic modalities.,Among the best approaches for understanding the molecular basis of COPD include gene expression profiling techniques, such as serial analysis of gene expression or microarrays.,Using these methods, recent studies have mapped comparative gene expression profiles of lung tissues from patients with different stages of COPD relative to healthy smokers or non-smokers.,Such studies have revealed a number of differentially-regulated genes associated with COPD progression, which include genes involved in the regulation of inflammation, extracellular matrix, cytokines, chemokines, apoptosis, and stress responses.,These studies have shed new light on the molecular mechanisms of COPD, and suggest novel targets for clinical treatments. | 1 |
Although subtypes of chronic obstructive pulmonary disease are recognized, it is unknown what happens to these subtypes over time.,Our objectives were to assess the stability of cluster-based subtypes in patients with stable disease and explore changes in clusters over 1 year.,Multiple correspondence and cluster analysis were used to evaluate data collected from 543 stable patients included consecutively from 5 respiratory outpatient clinics.,Four subtypes were identified.,Three of them, A, B, and C, had marked respiratory profiles with a continuum in severity of several variables, while the fourth, subtype D, had a more systemic profile with intermediate respiratory disease severity.,Subtype A was associated with less dyspnea, better health-related quality of life and lower Charlson comorbidity scores, and subtype C with the most severe dyspnea, and poorer pulmonary function and quality of life, while subtype B was between subtypes A and C.,Subtype D had higher rates of hospitalization the previous year, and comorbidities.,After 1 year, all clusters remained stable.,Generally, patients continued in the same subtype but 28% migrated to another cluster.,Together with movement across clusters, patients showed changes in certain characteristics (especially exercise capacity, some variables of pulmonary function and physical activity) and changes in outcomes (quality of life, hospitalization and mortality) depending on the new cluster they belonged to.,Chronic obstructive pulmonary disease clusters remained stable over 1 year.,Most patients stayed in their initial subtype cluster, but some moved to another subtype and accordingly had different outcomes. | Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality.,Patients with COPD are characterised by a reduced health status, which can be easily assessed by the COPD Assessment Test (CAT).,Previous studies show that health status can be worsened by the presence of comorbidities.,However, the impact of cardiovascular comorbidities on health status as assessed with CAT is not sufficiently investigated.,Therefore, the current study has the following objectives: (1) to study the clinical, (patho)physiological and psychosocial determinants of the CAT, and impact of previously established and/or newly diagnosed cardiovascular comorbidities on health status in tertiary care patients with COPD; (2) to assess the effects of pulmonary rehabilitation on CAT scores in patients with COPD; (3) to develop reference values for the CAT in Dutch elderly patients without COPD; and (4) to validate the CAT in a broad sample of Dutch patients with COPD.,The COPD, Health status and Comorbidities (Chance) study is a monocentre study consisting of an observational cross-sectional part and a longitudinal part.,Demographic and clinical characteristics will be assessed in primary care, secondary care and tertiary care patients with COPD, and in patients without COPD.,To assess health status, the CAT, Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) will be used.,The longitudinal part consists of a comprehensive pulmonary rehabilitation programme in 500 tertiary care patients.,For the cross-sectional part of the study, 150 patients without COPD, 100 primary care patients and 100 secondary care patients will be assessed during a single home visit.,The Medical Ethical Committee of the Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands (METC 11-3-070), has approved this study.,The study has been registered at the Dutch Trial Register (NTR 3416). | 1 |
This study evaluated the efficacy, safety and tolerability of the novel inhaled phosphodiesterase-4 inhibitor CHF6001 added-on to formoterol in patients with chronic obstructive pulmonary disease (COPD).,Randomised, double-blind, placebo- and active-controlled, parallel-group study.,Eligible patients had symptomatic COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) 30-70% predicted, and history of ≥1 moderate/severe exacerbation.,Patients were randomised to extrafine CHF6001 400, 800, 1200 or 1600 μg twice daily (BID), budesonide, or placebo for 24 weeks.,Primary objectives: To investigate CHF6001 dose-response for pre-dose FEV1 after 12 weeks, and to identify the optimal dose.,Moderate-to-severe exacerbations were a secondary endpoint.,Of 1130 patients randomised, 91.9% completed.,Changes from baseline in pre-dose FEV1 at Week 12 were small in all groups (including budesonide), with no CHF6001 dose-response, and no significant treatment-placebo differences.,For moderate-to-severe exacerbations, CHF6001 rate reductions versus placebo were 13-28% (non-significant).,In post-hoc analyses, CHF6001 effects were larger in patients with a chronic bronchitis phenotype (rate reductions versus placebo 24-37%; non-significant), and were further increased in patients with chronic bronchitis and eosinophil count ≥150 cells/μL (49-73%, statistically significant for CHF6001 800 and 1600 μg BID).,CHF6001 was well tolerated with no safety signal (including in terms of gastrointestinal adverse events).,CHF6001 had no effect in the primary lung function analysis, although was well-tolerated with no gastrointestinal adverse event signal.,Post-hoc analyses focused on exacerbation risk indicate specific patient subgroups who may receive particular benefit from CHF6001.,ClinicalTrials.gov (NCT02986321).,Registered 8 Dec 2016. | Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS).,We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.,The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone.,Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George’s Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).,In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts.,In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm.,In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm.,Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies.,ICS/LABA led to greater improvements in St George’s Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.,Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction.,Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations. | 1 |
Disorders of the lungs such as chronic obstructive pulmonary disease (COPD) are a major cause of chronic morbidity and mortality and the third leading cause of death in the world.,The absence of sensitive diagnostic tests for early disease stages of COPD results in under-diagnosis of this treatable disease in an estimated 60-85% of the patients.,In recent years a grating-based approach to X-ray dark-field contrast imaging has shown to be very sensitive for the detection and quantification of pulmonary emphysema in small animal models.,However, translation of this technique to imaging systems suitable for humans remains challenging and has not yet been reported.,In this manuscript, we present the first X-ray dark-field images of in-situ human lungs in a deceased body, demonstrating the feasibility of X-ray dark-field chest radiography on a human scale.,Results were correlated with findings of computed tomography imaging and autopsy.,The performance of the experimental radiography setup allows acquisition of multi-contrast chest X-ray images within clinical boundary conditions, including radiation dose.,Upcoming clinical studies will have to demonstrate that this technology has the potential to improve early diagnosis of COPD and pulmonary diseases in general. | To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.,Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival.,Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system.,Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950).,Median duration of follow-up was 7.4 years.,Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).,Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80).,There were 519 deaths in the study cohort.,Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001).,This increased mortality generally persisted after adjusting for LAA-950.,The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.,Online supplemental material is available for this article. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations.,However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.,Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed.,Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC).,The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations.,Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.,Compared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively).,In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC.,Neither FEV1 nor FVC was associated with cardiovascular risk.,Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).,Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks. | 1 |
► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | Oxidative stress has been implicated in the pathogenesis and progression of COPD.,Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden.,Structural changes to essential components of the lung are caused by oxidative stress, contributing to irreversible damage of both parenchyma and airway walls.,The antioxidant N-acetylcysteine (NAC), a glutathione precursor, has been applied in these patients to reduce symptoms, exacerbations, and the accelerated lung function decline.,This article reviews the available experimental and clinical data on the antioxidative effects of NAC in COPD, with emphasis on the role of exhaled biomarkers. | 1 |
Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone. | Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS).,Recommendations on their diagnosis are diffuse and inconsistent.,This survey aimed to identify consensus on criteria for diagnosing ACOS.,A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists.,Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis.,The two most frequently selected answers were considered as major criteria, others as minor criteria.,The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis.,Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient.,To diagnose ACOS in COPD patients, major criteria were “high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second ≥400 mL)” and “high degree of response to bronchodilators (>200 mL and ≥12% predicted above baseline)”.,Minor criteria were “personal/family history of atopy and/or IgE sensitivity to ≥1 airborne allergen”, “elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide”, “diagnosis of asthma <40 years of age”; “symptom variability”, and “age (in favor of asthma)”.,To diagnose ACOS in asthma patients, major criteria were “persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)” and “exposure to noxious particles/gases, with ≥10 pack-years for (ex-)smokers”; minor criteria were “lack of response on acute bronchodilator test”; “reduced diffusion capacity”; “limited variability in airway obstruction”; “age >40 years”; “emphysema on chest computed tomography scan”.,Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients.,These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health.,Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures.,This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations.,It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. | 1 |
The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.,Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014).,The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period.,Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year.,After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up.,A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.,In total 18,586 COPD patients were analyzed.,A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up.,Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up.,Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality.,Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both).,The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.,In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden. | Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Neutrophils are important effector cells of antimicrobial immunity in an acute inflammatory response, with a primary role in the clearance of extracellular pathogens.,However, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), there is excessive infiltration and activation of neutrophils, subsequent production of reactive oxygen species, and release of serine proteases, matrix metalloproteinases, and myeloperoxidase-resulting in collateral damage as the cells infiltrate into the tissue.,Increased neutrophil survival through dysregulated apoptosis facilitates continued release of neutrophil-derived mediators to perpetuate airway inflammation and tissue injury.,Several target mechanisms have been investigated to address pathologic neutrophil biology and thereby provide a novel therapy for respiratory disease.,These include neutrophil influx through inhibition of chemokine receptors CXCR2, CXCR1, and PI3Kγ signaling and neutrophil weaponry by protease inhibitors, targeting matrix metalloproteinases and neutrophil serine proteases.,In addition, neutrophil function can be modulated using selective PI3Kδ inhibitors.,This review highlights the latest advances in targeting neutrophils and their function, discusses the opportunities and risks of neutrophil inhibition, and explores how we might better develop future strategies to regulate neutrophil influx and function for respiratory diseases in dire need of novel effective therapies. | 1 |
COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease.,Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).,This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers.,Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks.,The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells.,Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.,Between July 2011 and May 2013, 89 patients were enrolled and randomized.,Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels.,Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline.,Changes in measures of inflammation and pulmonary function tests were not different among the groups.,Sulforaphane was well tolerated at both dose levels.,Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.,Clinicaltrials.gov: NCT01335971. | Chronic obstructive pulmonary disease (COPD) exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-κB activation.,RelB, an NF-κB family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown.,Moreover, there is no information on its association with clinical features of COPD.,The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation.,Data from 48 COPD patients were analyzed.,Blood samples were collected from stable-state and exacerbating patients.,After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess RelB, Cox-2, IL-8 and IL-1β mRNA expression and their associations with measured clinical variables.,Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation.,RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1β in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22)).,Cox-2, IL-8 and IL-1β were significantly associated with clinical features of patients in both stable-state and at exacerbation.,There was no association with RelB expression and any clinical features in COPD subjects at stable-state.,RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation.,RelB mRNA expression is lower than that of the other inflammatory mediators.,Expression of Cox-2, IL-8 and IL-1β were related to clinical features in both stable-state and at exacerbation.,However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD. | 1 |
The Clinical COPD Questionnaire (CCQ) is a simple patient-reported tool to measure clinical control of chronic obstructive pulmonary disease (COPD).,This open-label, single-arm, non-interventional study (NCT03663569) investigated changes in CCQ score during treatment with tiotropium/olodaterol in clinical practice.,Data were included from consenting COPD patients, enrolled in Bulgaria, Czech Republic, Hungary, Israel, Lithuania, Poland, Romania, Russia, Slovenia, Switzerland and Ukraine, who were receiving a new prescription for tiotropium/olodaterol according to the treating physician in a real-world environment.,The primary endpoint was the occurrence of therapeutic success, defined as a 0.4-point decrease in CCQ score after treatment with tiotropium/olodaterol for approximately 6 weeks.,Overall, 4819 patients were treated; baseline and Week 6 CCQ scores were available for 4700 patients, mostly classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B (51.6%) or D (42.7%).,After 6 weeks’ treatment, 81.4% (95% confidence interval [95% CI] 80.24-82.49) of patients achieved therapeutic success; mean improvement in overall CCQ score was 1.02 points (95% CI 1.00-1.05).,Improved CCQ score was seen in 92.2% of patients (95% CI 91.43-92.98), 2.5% had no change and 5.3% showed a worsening.,When stratified by prior treatment, the greatest benefit was seen in treatment-naïve patients, with 85.7% achieving therapeutic success, compared with 79.5% of those pretreated with long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) and 74.2% of those pretreated with LABA or long-acting muscarinic antagonist (LAMA) monotherapy.,Overall, rescue medication decreased by 1.25 puffs/day (95% CI 1.19-1.31) versus baseline.,In total, 29 patients (0.6%) reported drug-related adverse events and 7 patients reported serious adverse events (0.15%).,In 4700 COPD patients, 6 weeks’ treatment with tiotropium/olodaterol, as initial treatment or follow-up to LAMA or LABA monotherapy or LABA/ICS, improved CCQ and decreased rescue medication use.,The adverse event profile was consistent with the known safety profile of tiotropium/olodaterol. | Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | 1 |
The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases.,The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function.,We conducted a multi-center, cross-sectional study (“COPD Outcomes-based Network for Clinical Effectiveness & Research Translation” [CONCERT]).,We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires.,Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.,Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered.,Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed.,Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male).,More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L.,Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) correlated.,A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles.,Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients. | Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ. | 1 |
Remodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls.,Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling.,The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-β signalling in COPD patients of different GOLD stages.,Lung tissue sections of 14 smoking controls, 16 GOLD II and 19 GOLD IV patients were included and stained for elastin and collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2.,Elastin was significantly decreased in COPD patients not only in alveolar, but also in small airway walls.,Interestingly, both collagen and hyaluronan were increased in alveolar as well as small airway walls.,The matrix changes were highly comparable between GOLD stages, with collagen content in the alveolar wall increasing further in GOLD IV.,A calculated remodelling index, defined as elastin divided over collagen and hyaluronan, was decreased significantly in GOLD II and further lowered in GOLD IV patients, suggesting that matrix component alterations are involved in progressive airflow limitation.,Interestingly, there was a positive correlation present between the alveolar and small airway wall stainings of the matrix components, as well as for pSMAD2.,No differences in pSMAD2 staining between controls and COPD patients were found.,In conclusion, remodelling in the alveolar and small airway wall in COPD is markedly similar and already present in moderate COPD.,Notably, alveolar collagen and a remodelling index relate to lung function. | Asthma and chronic obstructive pulmonary disease (COPD) are characterized by different patterns of airway remodeling, which all include an increased mass of bronchial smooth muscle (BSM).,A remaining major question concerns the mechanisms underlying such a remodeling of BSM.,Because mitochondria play a major role in both cell proliferation and apoptosis, we hypothesized that mitochondrial activation in BSM could play a role in this remodeling.,We describe that both the mitochondrial mass and oxygen consumption were higher in the BSM from asthmatic subjects than in that from both COPD and controls.,This feature, which is specific to asthma, was related to an enhanced mitochondrial biogenesis through up-regulation of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A.,The priming event of such activation was an alteration in BSM calcium homeostasis.,BSM cell apoptosis was not different in the three groups of subjects.,Asthmatic BSM was, however, characterized by increased cell growth and proliferation.,Both characteristics were completely abrogated in mitochondria-deficient asthmatic BSM cells.,Conversely, in both COPD and control BSM cells, induction of mitochondrial biogenesis reproduced these characteristics.,Thus, BSM in asthmatic patients is characterized by an altered calcium homeostasis that increases mitochondrial biogenesis, which, in turn, enhances cell proliferation, leading to airway remodeling. | 1 |
Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | Implementation of noninvasive ventilation (NIV) as an add-on treatment has been routinely used in a non-intensive care setting since 2004 for patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure at a university hospital in Denmark.,Although randomized controlled trials show lowered mortality rates in highly selected patients with acute exacerbation and respiratory failure, there are only few reports on long-term survival after receiving NIV.,We present long-term all-cause mortality data from patients receiving NIV for the first time.,Data from medical records were retrospectively retrieved from all patients receiving NIV for the first time after being admitted acutely to an acute medical ward and further transfer to a respiratory ward with respiratory failure and a diagnosis of COPD in the period January 1, 2005 to December 31, 2007; patients were followed until January 2012.,Demographic data collected included age, sex, diagnoses at discharge, and, when present, FEV1; a “not-to-intubate” order was also registered when listed.,In total, 253 patients (143 female, 110 male) received NIV for the first time.,The median age was 72 years (range 46-91 years).,The 30-day mortality rate was 29.3%.,The 5-year survival rate was 23.7%.,Women showed a trend towards better survival than men (25.7% vs 19.2%, P = 0.25), and the trend was even more pronounced for patients with COPD.,The mortality rate of patients receiving NIV is high, as expected in a real-life setting, but with a 5-year survival rate of 23.7% with a trend towards more female than male long-term survivors. | 1 |
Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care.,We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation.,Implementation was then piloted using action research methodologies with patient input.,Actively involving staff was vital to ensure that the changes introduced were understood and the process followed.,Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice. | 1 |
Introduction of telehealth into the healthcare setting has been recognised as a service that might be experienced as disruptive.,This paper explores how this disruption is experienced.,In a longitudinal qualitative study, we conducted focus group discussions prior to and semi structured interviews post introduction of a telehealth service in Nottingham, U.K. with the community matrons, congestive heart failure nurses, chronic obstructive pulmonary disease nurses and community support workers that would be involved in order to elicit their preconceptions and reactions to the implementation.,Users experienced disruption due to the implementation of telehealth as threatening.,Three main factors add to the experience of threat and affect the decision to use the technology: change in clinical routines and increased workload; change in interactions with patients and fundamentals of face-to-face nursing work; and change in skills required with marginalisation of clinical expertise.,Since the introduction of telehealth can be experienced as threatening, managers and service providers should aim at minimising the disruption caused by taking the above factors on board.,This can be achieved by employing simple yet effective measures such as: providing timely, appropriate and context specific training; provision of adequate technical support; and procedures that allow a balance between the use of telehealth and personal visit by nurses delivering care to their patients. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | The aim of this study was to measure HrQoL during acute exacerbations of COPD using generic and disease-specific instruments, and to assess completeness, proportion with best or worst health state, sensitivity to change and discriminative ability for each instrument.,EQ-5D, SF-12 and SGRQ were obtained from COPD patients with GOLD stage III and IV hospitalized for an acute exacerbation both at admission and discharge.,To assess the instruments' properties, utility values were calculated for EQ-5D and SF-12, and a total score was derived from the SGRQ.,Mean utilities ranged from 0.54 (SF-12, stage IV) to 0.62 (EQ-5D, stage III) at admission, and from 0.58 (SF-12, stage IV) to 0.84 (EQ-5D, stage III) at discharge.,Completeness was best for EQ-5D and SGRQ, while no utility value for the SF-12 could be calculated for more than 30%.,For SGRQ subscales, the minimal score occurred in up to 11% at admission, while full health was observed for the EQ-5D at discharge in 13%.,Sensitivity to change was generally good, whereas discrimination between COPD stages was low for the EQ-5D.,Acute exacerbations seriously impair health status and quality of life.,The EQ-5D is generally suitable to measure HrQoL in exacerbations of severe COPD, although the high proportion of patients reporting full health at discharge poses a problem.,The main issue with the SF-12 is the high proportion of missing values in a self-assessed setting.,Properties of the SGRQ were satisfactory.,However, since no utility values can be derived from this disease-specific instrument, it is not suitable for cost-utility analyses in health-economic evaluations. | 1 |
•Self-management programmes are a popular way to engage patients in their own care.,•Inconclusive results stem from inconsistency in study conditions, design, and reporting.,•Behaviour change theories can identify appropriate outcome measures for evaluation.,•Programmes should be developed with theory and patient-centricity in mind.,Self-management programmes are a popular way to engage patients in their own care.,Inconclusive results stem from inconsistency in study conditions, design, and reporting.,Behaviour change theories can identify appropriate outcome measures for evaluation.,Programmes should be developed with theory and patient-centricity in mind.,The study aims to evaluate the ability of self-management programmes to change the healthcare-seeking behaviours of people with Chronic Obstructive Pulmonary Disease (COPD), and any associations between programme design and outcomes.,A systematic search of the literature returned randomised controlled trials of SMPs for COPD.,Change in healthcare utilisation was the primary outcome measure.,Programme design was analysed using the Theoretical Domains Framework (TDF).,A total of 26 papers described 19 SMPs.,The most common utilisation outcome was hospitalisation (n = 22).,Of these, 5 showed a significant decrease.,Two theoretical domains were evidenced in all programmes: skills and behavioural regulation.,All programmes evidenced at least 5 domains.,However, there was no clear association between TDF domains and utilisation.,Overall, study quality was moderate to poor.,This review highlights the need for more alignment in the goals, design, and evaluation of SMPs.,Specifically, the TDF could be used to guide programme design and evaluation in future.,Practices have a reasonable expectation that interventions they adopt will provide patient benefit and value for money.,Better design and reporting of SMP trials would address their ability to do so. | Effective self-management in chronic obstructive pulmonary disease (COPD) is crucial to reduce hospital admissions and improve outcomes for patients.,This includes early detection and treatment of exacerbations by patients themselves.,To explore patients’ current understanding and experience of managing and identifying COPD exacerbations at home.,A qualitative, interview-based study was carried out in patients’ homes.,Interviews were audio-recorded, transcribed and analysed using a grounded theory approach.,Forty-four patients (17 women, 27 men; age range 55-85 years), with moderate-to-very-severe COPD, were recruited to the interview study from primary and secondary care settings in Oxford, UK, during 2012-2013.,Patients identified exacerbations on the basis of measurable, ‘visible’ symptoms, such as cough and sputum and ‘invisible’ symptoms, such as chest sensations and bodily knowledge.,Most patients seemed to use a combination of these approaches when identifying exacerbations, according to the symptoms that had the most impact on their well-being.,Patients used additional self-management strategies during an exacerbation, such as self-medication (antibiotics and steroids) and monitored their recovery.,Contact with health-care professionals usually occurred when patients felt no longer able to manage themselves.,Patients use both assessment of objective biomarkers, which are aligned with medical knowledge, and subjective symptoms based on their experience, to identify and manage exacerbations of COPD.,Health-care professionals and clinicians should acknowledge this ‘expert patient’ knowledge and integrate this into patients’ care plans to facilitate early recognition and treatment of exacerbations. | 1 |
Cigarette smoke is the main risk factor of pulmonary emphysema development, which is characterized by alveolar wall destruction.,Mitochondria are important for alveolar type II (ATII) cell metabolism due to ATP generation.,We isolated ATII cells from control non-smoker and smoker organ donors, and after lung transplant of patients with emphysema to determine mitochondrial function, dynamics and mitochondrial (mt) DNA damage.,We found high mitochondrial superoxide generation and mtDNA damage in ATII cells in emphysema.,This correlated with decreased mtDNA amount.,We also detected high TOP1-cc and low TDP1 levels in mitochondria in ATII cells in emphysema.,This contributed to the decreased resolution of TOP1-cc leading to accumulation of mtDNA damage and mitochondrial dysfunction.,Moreover, we used lung tissue obtained from areas with mild and severe emphysema from the same patients.,We found a correlation between the impaired fusion and fission as indicated by low MFN1, OPA1, FIS1, and p-DRP1 levels and this disease severity.,We detected lower TDP1 expression in severe compared to mild emphysema.,We found high DNA damage and impairment of DNA damage repair in mitochondria in ATII cells isolated from emphysema patients, which contribute to abnormal mitochondrial dynamics.,Our findings provide molecular mechanisms of mitochondrial dysfunction in this disease.,This work was supported by National Institutes of Health (NIH) grant R01 HL118171 (B.K.) and the Catalyst Award from the American Lung Association (K.B.). | Loss of skeletal muscle mitochondrial oxidative capacity is well-established in patients with COPD, but the role of mitochondrial breakdown herein is largely unexplored.,Currently, we studied if mitochondrial breakdown signalling is increased in skeletal muscle of COPD patients and associates with the loss of mitochondrial content, and whether it is affected in patients with iron deficiency (ID) or systemic inflammation.,Therefore, mitophagy, autophagy, mitochondrial dynamics and content markers were analysed in vastus lateralis biopsies of COPD patients (N = 95, FEV1% predicted: 39.0 [31.0-53.6]) and healthy controls (N = 15, FEV1% predicted: 112.8 [107.5-125.5]).,Sub-analyses were performed on patients stratified by ID or C-reactive protein (CRP).,Compared with controls, COPD patients had lower muscle mitochondrial content, higher BNIP3L and lower FUNDC1 protein, and higher Parkin protein and gene-expression.,BNIP3L and Parkin protein levels inversely correlated with mtDNA/gDNA ratio and FEV1% predicted.,ID-COPD patients had lower BNIP3L protein and higher BNIP3 gene-expression, while high CRP patients had higher BNIP3 and autophagy-related protein levels.,In conclusion, our data indicates that mitochondrial breakdown signalling is increased in skeletal muscle of COPD patients, and is related to disease severity and loss of mitochondrial content.,Moreover, systemic inflammation is associated with higher BNIP3 and autophagy-related protein levels. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users. | To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data.,Primary care; Lothian (population approximately 800 000), Scotland.,Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record.,Patients were followed up until 2010, death or they left a participating practice.,First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care.,1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission.,Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model.,More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model.,High BMI was associated with a lower risk of first AECOPD admission and readmission.,Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission.,Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission.,The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. | 1 |
Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk.,However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited.,The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations.,After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model.,In addition, the population-attributable fractions (PAFs) were also calculated, and a subgroup analysis was conducted.,Heterogeneity was assessed by I2.,In total, 59 studies were included.,In the single-pollutant model, the risks of COPD were calculated by each 10 μg/m3 increase in pollutant concentrations, with the exception of CO (100 μg/m3).,There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants.,The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively.,The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously.,When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants.,The adverse health effects of SO2 and NO2 exposure were more significant in low-/middle-income countries than in high-income countries: SO2, relative risk: 1.012 (95% confidence interval: 1.001, 1.023); and NO2, relative risk: 1.019 (95% confidence interval: 1.014, 1.024).,Short-term exposure to air pollutants increases the burden of risk of COPD acute exacerbations significantly.,Controlling ambient air pollution would provide benefits to COPD patients. | Standardised evidenced-based materials and mechanisms to facilitate the delivery of the education component of pulmonary rehabilitation are not widely available.,The aims of this study were: 1) to adapt the self-management programme Living Well with COPD (LWWCOPD) programme, for embedding in pulmonary rehabilitation; and, 2) to conduct a process evaluation of the adapted programme.,The adaptations to the LWWCOPD programme were informed by focus groups, current practice, relevant research and guideline documents.,Pulmonary rehabilitation sites used the adapted programme, the LWWCOPD programme for pulmonary rehabilitation, to deliver the education component of pulmonary rehabilitation.,A process evaluation was conducted: elements included reach (patients’ attendance rates), dose delivered (amount of programme delivered), dose received (health professional and patient satisfaction) and fidelity (impact on patients’ knowledge, understanding and self-efficacy on the Understanding COPD questionnaire).,Descriptive statistics (mean, SD) were used to summarise demographics and key data from the feedback questionnaires.,Qualitative feedback on the programme was collated and categorised.,Changes in the Understanding COPD questionnaire were examined using paired t-tests.,The LWWCOPD programme for pulmonary rehabilitation was delivered in eleven hospital- and community-based programmes (n=25 health professionals, n=57 patients with COPD).,It consisted of six weekly 30-45 minute sessions.,The process evaluation showed positive results: 62.3% of patients attended ≥ 4 education sessions (reach); mean (SD) 90 (10)% of the session content were delivered (dose delivered); the majority of sessions were rated as excellent or good by health professionals and patients.,Patients’ satisfaction was high: mean (SD) Section B of the Understanding COPD questionnaire: 91.67 (9.55)% (dose received).,Knowledge, understanding and self-efficacy improved significantly: mean change (95% CI): Section A of the Understanding COPD questionnaire: 26.75 (21.74 to 31.76)%, BCKQ 10.64 (6.92 to 14.37)% (fidelity).,This rigorous process evaluation has demonstrated that the LWWCOPD programme for pulmonary rehabilitation can be used to deliver high quality, consistent and equitable education sessions during hospital and community-based pulmonary rehabilitation.,This programme is now available worldwide (http://www.livingwellwithcopd.com/living-well-and-pulmonary-rehabilitation.html).,This study was registered with clinicaltrials.gov (reference number: NCT01226836) | 1 |
The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).,This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD.,The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin −50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84.,Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St.,George’s Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.,Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) −29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND.,The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference −23 mL; 95 % CI −54 to 8 mL).,The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores.,The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.,UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.,ClinicalTrials.gov study ID NCT02257385; GSK study no.,116961.,The online version of this article (doi:10.1007/s40268-016-0131-2) contains supplementary material, which is available to authorized users. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 1 |
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route.,Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month.,After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT.,After 1 week, mice were euthanized.,Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue.,In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC).,Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor.,Only BM-MSCs (IV > IT) increased the number of M2 macrophages.,In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2. | The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters.,Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema.,MSCs were administered intratracheally or intravenously, before or after elastase injection.,Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration.,Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up.,Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up.,Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology.,Intratracheal MSC treatment did not modify lung function or histology.,In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema.,Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function.,Intratracheal MSC treatment had no effect on lung function or histology. | 1 |
Baduanjin exercise is a traditional Chinese health Qigong routine created by an ancient physician for health promotion.,Its mild-to-moderate exercise intensity is suitable for individuals with medical conditions.,Recently, a large number of trials have been conducted to investigate the effects of Baduanjin exercise in patients with chronic obstructive pulmonary disease (COPD).,It remains to be determined whether Baduanjin exercise prescription is beneficial for the management of COPD patients.,Thus, we conducted a systematic review to objectively evaluate the existing literature on this topic.,We searched six databases (PubMed, Web of Science, Cochrane Library, Scopus, China National Knowledge Infrastructure, and Wanfang) from inception until early May 2018.,The adapted Physical Therapy Evidence Database (PEDro) scale was used for study quality assessment of all randomized controlled trials (RCTs).,Based on 95% confidence interval (CI), the pooled effect size (Hedge’s g) of exercise capability (6-Minute Walking Test, 6-MWT), lung function parameters (forced expiratory volume in one second, FEV1; forced volume vital capacity, FVC; FEV1/FVC ratio), and quality of life were calculated based on the random-effects model.,Twenty RCTs (n = 1975 COPD patients) were included in this review, with sum scores of the adapted PEDro scale between 5 and 9.,Study results of the meta-analysis indicate that Baduanjin is effective in improving exercise capability (Hedge’s g = 0.69, CI 0.44 to 0.94, p < 0.001, I2 = 66%), FEV1 (Hedge’s g = 0.47, CI 0.22 to 0.73, p < 0.001, I2 = 68.01%), FEV1% (Hedge’s g = 0.38, CI 0.21 to 0.56, p < 0.001, I2 = 54.74%), FVC (Hedge’s g = 0.39, CI 0.22 to 0.56, p < 0.001, I2 = 14.57%), FEV1/FVC (Hedge’s g = 0.5, CI 0.33 to 0.68, p < 0.001, I2 = 53.49%), and the quality of life of COPD patients (Hedge’s g = −0.45, CI −0.77 to −0.12, p < 0.05, I2 = 77.02%), as compared to control groups.,Baduanjin exercise as an adjunctive treatment may potentially improve exercise capability and pulmonary function of COPD patients as well as quality of life.,Baduanjin exercise could be tentatively prescribed for COPD in combination with the conventional rehabilitation program to quicken the process of recovery.,To confirm the positive effects of Baduanjin exercise for COPD patients, future researchers need to consider our suggestions mentioned in this article. | The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent.,Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent.,The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors.,Pathological changes in COPD are observed in central airways, small airways and alveolar space.,The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair.,Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70.,COPD is characterized by an accelerated decline in FEV1.,Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline.,The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy.,COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor.,Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support.,Lung volume reduction surgery and lung transplantation are advised in selected severe patients.,Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations. | 1 |
We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables.,All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydın province, a city located in the western part of Turkey, were included in this study.,The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated.,For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded.,The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees.,The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001).,Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all).,Comorbidities have an important role in the total costs of acute exacerbations of COPD.,Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD. | To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.,A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution.,The patients underwent dual-energy X-ray absorptiometry.,The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects.,Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.,We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2.,Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status.,Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction).,The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001).,Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009).,The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.,In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.,Avaliar a prevalência de sarcopenia em pacientes com DPOC e determinar se sarcopenia está correlacionada com a gravidade e o prognóstico de DPOC.,Estudo retrospectivo em pacientes com DPOC atendidos no ambulatório de pneumologia de nossa instituição.,Os pacientes realizaram absorciometria de dupla energia por raios X.,O diagnóstico de sarcopenia foi baseado no índice de massa muscular esquelética, definido como massa magra apendicular/altura2 somente para indivíduos com baixo peso, sendo ajustado pela massa gorda para aqueles com peso normal/sobrepeso.,A gravidade da doença (estádio da DPOC) foi avaliada com os critérios da Global Initiative for Chronic Obstructive Lung Disease (GOLD).,O grau de obstrução e o prognóstico foram determinados pelo índice Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE).,Foram incluídos 91 pacientes (50 mulheres), com média de idade de 67,4 ± 8,7 anos e média de IMC de 25,8 ± 6,1 kg/m2.,Sarcopenia foi diagnosticada em 36 (39,6%) dos pacientes, sem diferenças relacionadas a sexo, idade ou status tabágico.,Não houve associação de sarcopenia com estádios GOLD ou VEF1 (utilizado como indicador do grau de obstrução).,O IMC, a porcentagem de gordura corporal e a massa magra total foram menores nos pacientes com sarcopenia do que naqueles sem a doença (p < 0,001).,A prevalência de sarcopenia foi maior nos pacientes com BODE nos quartis 3 ou 4 que naqueles com BODE nos quartis 1 ou 2 (p = 0,009).,A análise multivariada mostrou que os quartis do BODE estavam significativamente associados à sarcopenia, independentemente de idade, gênero, status tabágico e estádio GOLD.,Em pacientes com DPOC, sarcopenia parece estar associada a alterações desfavoráveis na composição corporal e pior prognóstico. | 1 |
Severe hyperinflation causes detrimental effects such as dyspnea and reduced exercise capacity and is an independent predictor of mortality in COPD patients.,Static lung volumes are required to diagnose severe hyperinflation, which are not always accessible in primary care.,Several studies have shown that the area under the forced expiratory flow-volume loop (AreaFE) is highly sensitive to bronchodilator response and is correlated with residual volume/total lung capacity (RV/TLC), a common index of air trapping.,In this study, we investigate the role of AreaFE% (AreaFE expressed as a percentage of reference value) and conventional spirometry parameters in indicating severe hyperinflation.,We used a cohort of 215 individuals with COPD.,The presence of severe hyperinflation was defined as elevated air trapping (RV/TLC >60%) or reduced inspiratory fraction (inspiratory capacity [IC]/TLC <25%) measured using body plethysmography.,AreaFE% was calculated by integrating the maximal expiratory flow-volume loop with the trapezoidal rule and expressing it as a percentage of the reference value estimated using predicted values of FVC, peak expiratory flow and forced expiratory flow at 25%, 50% and 75% of FVC.,Receiver operating characteristics (ROC) curve analysis was used to identify cut-offs that were used to indicate severe hyperinflation, which were then validated in a separate group of 104 COPD subjects.,ROC analysis identified cut-offs of 15% and 20% for AreaFE% in indicating RV/TLC >60% and IC/TLC <25%, respectively (N=215).,On validation (N=104), these cut-offs consistently registered the highest accuracy (80% each), sensitivity (68% and 75%) and specificity (83% and 80%) among conventional parameters in both criteria of severe hyperinflation.,AreaFE% consistently provides a superior estimation of severe hyperinflation using different indices, and may provide a convenient way to refer COPD patients for body plethysmography to address static lung volumes. | Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality.,It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient.,Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases.,Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model.,604 patients were included (mean±sd age 61.9±9.7 years; forced expiratory volume in 1 s 37±18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months.,Median survival was 91.9 (95% CI 80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively.,Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172-0.639; and second quartile (51-37.3%): HR 0.52, 95% CI 0.322-0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02-1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77-0.94) were the only parameters independently associated with mortality.,Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.,Transfer factor not GOLD stage is the most powerful predictor of survival in patients with COPDhttp://ow.ly/mGmjG | 1 |
Data suggesting that low physical activity levels are associated with increased mortality and exacerbations in patients with COPD have led to increasing interest in the role of physical activity in COPD.,This study evaluated self-reported functional performance, a measure of physical activity impairment, according to current treatment regimen, lung function, symptoms, and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 groups in a large sample of patients with COPD.,This multicenter, cross-sectional, observational study (study identifier: D5970R00003) included patients with COPD (≥40 years) in the USA.,A self-completion questionnaire captured demographics and patient-reported outcomes, including the Functional Performance Inventory-Short Form (FPI-SF).,Diagnosis and treatment history (including spirometry results) were extracted from medical charts.,Multiple linear regression was used to determine the relationship between FPI-SF and FEV1 % predicted, and FPI-SF and COPD assessment test (CAT) score.,Overall, 1,775 patients participated (classified as GOLD 2017 group A, 14.8%; B, 46.6%; C, 2.6%; D, 36.0%).,Physical activity impairment affected patients across all treatment regimens and GOLD groups (mean FPI-SF total score: 2.1), with the greatest impairment within FPI-SF observed for domains requiring most physical exertion, “physical exercise” and “maintaining the household” (mean FPI-SF scores: 1.7 and 1.8, respectively).,Patients receiving loose triple therapy and those in GOLD group D had the highest impairment (mean FPI-SF total scores: both 1.9), and the lowest FEV1 % predicted (55.5% and 54.7%, respectively).,FPI-SF total score correlated with FEV1 % predicted and more strongly with CAT score (all P<0.05).,The stronger correlation between FPI-SF and CAT scores compared to FPI-SF and FEV1 % predicted suggests that symptoms may have a greater impact on patients’ functional performance than lung function.,Further longitudinal studies are required to establish a correlation between the effect of treatment on symptoms, lung function, and physical activity. | Purpose.,This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD.,Patients and Methods.,We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR).,In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA.,Data were analyzed using simple and logistic regression and receiver operating characteristic analyses.,Results.,Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01).,Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001).,Conclusion.,Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD. | 1 |
Currently, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide.,The determination of immune mechanisms of inflammation in the disease presents an important challenge for fundamental medical research.,According to modern views, Toll-like receptors (TLRs), among which TLR2 and TLR4 play a key role, are one of the essential components of inflammatory process in COPD.,This review focuses on following aspects: the role of TLR2 and TLR4 in the initiation of inflammatory process in COPD; the mechanisms of influence of various exogenous factors (cigarette smoke, suspended particulate matter, and bacteria) on the expression of TLR2 and TLR4; the contribution of these TLRs to the T-helper (Th) immune response development in COPD, in particular to the Th17 immune response, which contributes to the progression of the disease and therapeutic implications of TLR2 and TLR4 in COPD. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Chronic obstructive pulmonary disease (COPD) has significant systemic effects that substantially impact quality of life and survival.,The purpose of this study was to assess and compare peripheral muscle strength and endurance, exercise capacity, fatigue perception and quality of life between patients with COPD and healthy subjects.,Twenty COPD patients (mean FEV1 49.3 ± 19.2%) and 20 healthy subjects were included in the study.,Pulmonary function testing and six-minute walk test (6MWT) were performed.,Peripheral muscle strength was measured with a hand-held dynamometer, peripheral muscle endurance was evaluated with sit-ups, squats and modified push-ups tests.,Fatigue perception was assessed using the Fatigue Impact Scale (FIS) and Fatigue Severity Scale (FSS).,General quality of life was determined with the Nottingham Health Profile (NHP), and cough-specific quality of life was evaluated with the Leicester Cough Questionnaire (LCQ).,Pulmonary functions, strength of shoulder abductor and flexor muscles, numbers of sit-ups and squats, 6MWT distance and 6MWT% were significantly lower in COPD patients than in healthy subjects (p < 0.05).,FIS psychosocial sub-dimension and total scores, NHP scores for all sub-dimensions except pain sub-dimension of the COPD group were significantly higher than those of healthy subjects (p < 0.05).,The LCQ physical, psychological and social sub-dimensions and total scores were significantly lower in COPD patients than in healthy subjects (p < 0.05).,Pulmonary functions, peripheral muscle strength and endurance, exercise capacity and quality of life were adversely affected in patients with COPD.,There are greater effect of fatigue on psychosocial functioning and general daily life activities and effect of cough on the quality of life in patients with COPD.,This study supports the idea that COPD patients must be evaluated in a comprehensive manner for planning pulmonary rehabilitation programs. | Fatigue in COPD impairs functional status; however there are few studies examining mechanistic pathways of this symptom.,The aims of this study are to compare fatigue between COPD patients and healthy age-matched subjects, and to identify predictors of fatigue in COPD.,Seventy four COPD patients, mean age 69.9 (49-87) yrs, mean (SD) % predicted FEV1 46.5 (20.0) % and FEV1/FVC ratio 0.45 (0.13) and 35 healthy subjects, mean age 67.1 (50-84) yrs completed the Multidimensional Fatigue Inventory (MFI 20).,Patients' assessment included Depression (HADS), lung function, BMI, muscle strength, incremental shuttle walk test (ISWT), exercise oxygen saturation (SpO2), Borg breathlessness (CR-10) and exertion (RPE).,Serum level of Interleukin 6 (IL-6) was recorded.,Differences in MFI 20 between groups were examined and predictors of fatigue identified using logistic regression.,Significant differences (p < 0.01) were found between the COPD and healthy subjects for all MFI 20 dimensions.,There were significant differences when classified according to GOLD and dyspnoea stages for selected dimensions only.,Predictors of General Fatigue were depression, muscle strength and end SpO2 (R2 = .62); of Physical Fatigue: depression, % predicted FEV1, ISWT and age (R2 = .57); Reduced Activity: % predicted FEV1, BMI and depression (R2 = .36); Reduced Motivation: RPE, depression and end SpO2 (R2 = .37) and Mental Fatigue: depression and end SpO2 (R2 = .38).,All dimensions of fatigue were higher in COPD than healthy aged subjects.,Predictive factors differ according to the dimension of fatigue under investigation.,COPD-RF is a multi component symptom requiring further consideration. | 1 |
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation.,Why some patients are susceptible to colonisation is not understood.,We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.,The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD.,Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.,BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls.,NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation.,When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM.,We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway.,Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients.,This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. | The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2-agonist (LABA) treatment in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) compared to patients with COPD alone has rarely been examined.,This study aimed to evaluate the clinical efficacy for the improvement of lung function after ICS/LABA treatment in patients with ACOS compared to COPD alone patients.,Patients with stable COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort.,Subjects began a 3-month ICS/LABA treatment after a washout period.,ACOS was defined when the patients had 1) a personal history of asthma, irrespective of age, and wheezing in the last 12 months in a self-reported survey and 2) a positive bronchodilator response.,Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for ACOS.,After a 3-month treatment with ICS/LABA, the increase in forced expiratory volume in 1 second (FEV1) was significantly greater in ACOS patients than in those with COPD alone (240.2±33.5 vs 124.6±19.8 mL, P=0.002).,This increase in FEV1 persisted even after adjustment for confounding factors (adjusted P=0.002).,According to severity of baseline FEV1, the ACOS group showed a significantly greater increase in FEV1 than the COPD-alone group in patients with mild-to-moderate airflow limitation (223.2±42.9 vs 84.6±25.3 mL, P=0.005), whereas there was no statistically significant difference in patients with severe to very severe airflow limitation.,This study provides clinical evidence that ACOS patients with mild-to-moderate airflow limitation showed a greater response in lung function after 3 months of ICS/LABA combination treatment. | 1 |
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations.,The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract.,The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations.,In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD.,In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes.,This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. | Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults suffering obstructive lung diseases.,Existing evidence associates chronic infection by NTHi to the progression of the chronic respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed.,To provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease.,Pulse field gel electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains.,Phenotypic characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance to antimicrobial peptides (AMP).,Persistent isolates differed from new strains in showing low epithelial adhesion and inability to form biofilms when grown under continuous-flow culture conditions in microfermenters.,Self-aggregation clustered the strains by patient, not by persistence.,Increasing resistance to AMPs was observed for each series of persistent isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation.,Variation was further analyzed for the series of three persistent isolates recovered from patient 1.,These isolates displayed comparable growth rate, natural transformation frequency and murine pulmonary infection.,Genome sequencing of these three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter ompP1, and the phosphoribosylamine glycine ligase purD.,Collectively, we frame a range of pathogenic traits and a repertoire of genetic variants in the context of persistent infection by NTHi. | 1 |
Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis.,Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways.,Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD.,The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.,Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals.,Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.,Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio.,In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).,Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort.,The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes. | The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden.,The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency.,Most of these studies were association studies, rather than confirmatory studies.,More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits.,More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD. | 1 |
Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease.,We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort.,We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter.,Patients were dichotomized as frequent (≥2 AECOPD/year) or infrequent exacerbators.,Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline.,The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95 % CI, 1.24-7.14, p = 0.01).,The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]).,Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum.,However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test).,In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival.,The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989.,The online version of this article (doi:10.1186/s12931-015-0306-3) contains supplementary material, which is available to authorized users. | To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities.,The ESMI study is a multicenter observational study.,Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included.,The clinical characteristics, treatments, and comorbidities were gathered.,The results of conventional sputum cultures were recorded.,A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%).,The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026).,Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005).,Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity.,The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities. | 1 |
Phenotyping of chronic bronchitis (CB) using COPD assessment tool (CAT) scores and St George’s Respiratory Questionnaire (SGRQ) has rarely been attempted.,The present study defined CB using CAT 1 and 2 scores and the questions on the severity of cough and sputum from the SGRQ.,Furthermore, the predictability of CT parameters was also assessed for each CB definition.,Patients enrolled in the Korean Obstructive Lung Disease study from June 2005 to October 2015 were evaluated for this study.,The patients were spirometrically diagnosed with COPD and had a smoking history of >10 pack-years.,Volumetric CT scans were performed for each patient upon enrollment in the cohort.,Two definitions of CB using CAT 1/2 scores and SGRQ questions were used to phenotype CB among the study patients.,Receiver operating characteristic curve analysis was performed to estimate the predictability of CT parameters for the CB phenotypes.,Using CAT 1/2 scores, 57 of 279 (20.4%) patients had CB, and 178 of 573 (31.1%) had CB when the SGRQ questions were used to phenotype it.,Total CAT and SGRQ scores were significantly higher in the CB group than those in the non-CB group for both definitions of CB.,Forced expiratory volume in 1 second was lower for both CAT-defined and SGRQ-defined CB than that in the non-CB group.,Mean wall thickness was significantly higher for both CB groups than in the non-CB group.,Expiratory lung volume was higher and mean lung density was significantly lower for the SGRQ-defined CB group than non-CB group.,The 2 CB definitions using CAT scores and the SGRQ questions correlated with associated CT airway parameters.,SGRQ-defined CB better reflected the accompaniment of small airway obstruction when compared with CAT-defined CB. | Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) and lung cancer, closely related to smoking, are major lung diseases affecting millions of individuals worldwide.,The generated gas mixture of smoking is proved to contain about 4,500 components such as carbon monoxide, nicotine, oxidants, fine particulate matter, and aldehydes.,These components were considered to be the principle factor driving the pathogenesis and progression of pulmonary disease.,A large proportion of lung cancer patients showed a history of COPD, which demonstrated that there might be a close relationship between COPD and lung cancer.,In the early stages of smoking, lung barrier provoked protective response and DNA repair are likely to suppress these changes to a certain extent.,In the presence of long-term smoking exposure, these mechanisms seem to be malfunctioned and lead to disease progression.,The infiltration of inflammatory cells to mucosa, submucosa, and glandular tissue caused by inhaled cigarette smoke is responsible for the destruction of matrix, blood supply shortage, and epithelial cell death.,Conversely, cancer cells have the capacity to modulate the proliferation of epithelial cells and produce of new vascular networks.,Comprehension understanding of mechanisms responsible for both pathologies is necessary for the prevention and treatment of COPD and lung cancer.,In this review, we will summarize related articles and give a glance of possible mechanism between cigarette smoking induced COPD and lung cancer. | There is growing evidence about sex-related phenotypes of COPD.,However, the sex differences in COPD mainly result from smokers.,This study evaluated the sex differences in nonsmoking patients with COPD, focusing on structural changes in the lungs in airway diseases and emphysema.,Ninety-seven nonsmoking patients, defined as having <1 pack-year of lifetime cigarette smoking, diagnosed with COPD were selected from a Korean COPD cohort.,Emphysema extent and mean wall area percentage (WA%) on computed tomography were compared between the male and female groups.,The 97 patients with COPD included 62 females and 35 males.,Emphysema index was significantly lower (3.5±4.2 vs 6.2±5.7, P<0.01) and mean WA% on computed tomography was significantly higher (71.8%±5% vs 69.4%±5%, P<0.01) in females than in males, after adjusting for age, body mass index, history of biomass exposure, and postbronchodilator forced expiratory volume in 1 second (% of predicted).,WA% was higher and emphysema extent was lower in nonsmoking females with COPD than in nonsmoking males with COPD.,These findings suggest that males may be predisposed to an emphysema phenotype and females may be predisposed to an airway phenotype of COPD. | 1 |
Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status.,Design Prospective, randomised controlled trial.,Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom.,Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193).,Main outcome measures The primary outcome was readmission rate at 12 months.,Secondary outcomes included number of hospital days, mortality, physical performance, and health status.,The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome.,Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission.,The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training.,Patients also received a self management and education package.,Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group).,No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4).,An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03).,Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year.,Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months.,Mortality at 12 months was higher in the intervention group.,The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.,Trial registration Current Controlled Trials ISRCTN05557928. | Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).,Design Population based longitudinal consecutive cohort study.,Setting Centres prescribing long term oxygen therapy in Sweden.,Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.,Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.,Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation.,No patient was lost to follow-up.,Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively.,Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend.,Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44).,Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99).,Associations were not modified by being naive to the drugs or by hypercapnia.,Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease. | 1 |
Purpose.,This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD.,Patients and Methods.,We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR).,In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA.,Data were analyzed using simple and logistic regression and receiver operating characteristic analyses.,Results.,Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01).,Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001).,Conclusion.,Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD. | Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide.,Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility.,We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort.,We assessed DNA methylation from whole blood samples in 362 African-American smokers in the PA-SCOPE cohort using the Illumina Infinium HumanMethylation27 BeadChip Array.,Final analysis included 19302 CpG probes annotated to the nearest gene transcript after quality control.,We tested methylation associations with COPD case-control status using mixed linear models.,Weighted gene comethylation networks were constructed using weighted gene coexpression network analysis (WGCNA) and network modules were analyzed for association with COPD.,There were five differentially methylated CpG probes significantly associated with COPD among African-Americans at an FDR less than 5 %, and seven additional probes that approached significance at an FDR less than 10 %.,The top ranked gene association was MAML1, which has been shown to affect NOTCH-dependent angiogenesis in murine lung.,Network modeling yielded the “yellow” and “blue” comethylation modules which were significantly associated with COPD (p-value 4 × 10-10 and 4 × 10-9, respectively).,The yellow module was enriched for gene sets related to inflammatory pathways known to be relevant to COPD.,The blue module contained the top ranked genes in the concurrent differential methylation analysis (FXYD1/LGI4, gene significance p-value 1.2 × 10-26; MAML1, p-value 2.0 × 10-26; CD72, p-value 2.1 × 10-25; and LPO, p-value 7.2 × 10-25), and was significantly associated with lung development processes in Gene Ontology gene-set enrichment analysis.,We identified 12 differentially methylated CpG sites associated with COPD that mapped to biologically plausible genes.,Network module comethylation patterns have identified candidate genes that may be contributing to racial differences in COPD susceptibility and severity.,COPD-associated comethylation modules contained genes previously associated with lung disease and inflammation and recapitulated known COPD-associated genes.,The genes implicated by differential methylation and WGCNA analysis may provide mechanistic targets contributing to COPD susceptibility, exacerbations, and outcomes among African-Americans.,Trial Registration: NCT00774176, Registry: ClinicalTrials.gov, URL: www.clinicaltrials.gov, Date of Enrollment of First Participant: June 2004, Date Registered: 04 January 2008 (retrospectively registered).,The online version of this article (doi:10.1186/s12931-016-0459-8) contains supplementary material, which is available to authorized users. | 1 |
There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course.,Previous studies on this topic did not generate causally-interpretable estimates.,Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients.,Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes.,We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events.,Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics.,35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up.,The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations.,This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event.,The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality.,There was substantial heterogeneity in the individual-specific rate of severe exacerbations.,Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile.,Using robust statistical methodology that controlled for heterogeneity in exacerbation rates among individuals, we demonstrated potential causal associations among past and future severe exacerbations, albeit the magnitude of association was noticeably lower than previously reported.,The prevention of severe exacerbations has the potential to modify the disease trajectory. | A previous study explored factors discriminating colonization and true infection among non-transplant, non-neutropenic patients with repeated Aspergillus spp. isolation from lower respiratory samples.,The present study explored the evolution of patients with Aspergillus colonization in that study to determine the percentage of cases progressing to aspergillosis and time to development.,Clinical records were retrospectively reviewed (for each patient from his end date in the past study) and data from all respiratory processes suffered by patients up to April 2015 were recorded.,Comparisons of variables were performed between colonized patients that developed aspergillosis and those that did not.,A Kaplan-Meier curve was used to describe time to development of aspergillosis in chronic obstructive pulmonary disease (COPD) patients for II-IV stages of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification.,Sixty seven colonized patients were followed, 12 of them (17.9%) developed aspergillosis.,Diagnoses included six tracheobronchitis (4 invasive, 2 simple tracheobronchitis), four pulmonary disease (2 invasive pulmonary aspergillosis, 2 chronic pulmonary aspergillosis), one allergic bronchopulmonary aspergillosis and one pulmonary aspergilloma.,Up to 47 (70.4%) of the study patients presented COPD.,Among patients developing aspergillosis COPD was more frequent (100%) than among those that did not develop aspergillosis (35 out of 55; 63.6%) (p = 0.012), as well as GOLD IV patients were more frequent among COPD patients developing aspergillosis than among COPD patients that did not (50.0 vs.,26.1%, p = 0.046).,Mean time to development of aspergillosis was 18.4 months (median: 8.5) with a wide range (1-58).,Overtime, the percentage of patients developing aspergillosis was significantly higher among GOLD IV patients than among GOLD II-III patients (p = 0.032).,The high percentage of cases progressing to aspergillosis among colonized patients, especially among those with COPD (25.5%), stresses the importance of colonization as risk factor, and creates awareness of the possible change from colonization to invasive disease in GOLD IV patients. | 1 |
There is an ongoing demand for easily accessible biomarkers that reflect the physiological and pathophysiological mechanisms of COPD.,To test if an exercise challenge could help to identify clinically relevant metabolic biomarkers in COPD.,We performed two constant-load exercise challenges separated by 4 weeks including smokers with COPD (n=23/19) and sex- and age-matched healthy smokers (n=23/20).,Two hours after a standardized meal venous blood samples were obtained before, 5 mins after the start, at the end of submaximal exercise, and following a recovery of 20 mins.,Data analysis was performed using mixed- effects model, with the metabolite level as a function of disease, time point and interaction terms and using each individual's resting level as reference.,Exercise duration was longer in healthy smokers but lactate levels were comparable between groups at all four time points.,Glucose levels were increased in COPD.,Glutamine was lower, while glutamate and arginine were higher in COPD.,Branched-chain amino acids showed a stronger decline during exercise in healthy smokers.,Carnitine and the acyl-carnitines C16 and C18:1 were increased in COPD.,These metabolite levels and changes were reproducible in the second challenge.,Higher serum glucose, evidence for impaired utilization of amino acids during exercise and a shift of energy metabolism to enhanced consumption of lipids could be early signs for a developing metabolic syndrome in COPD.,In COPD patients, deviations of energy and nitrogen metabolism are amplified by an exercise challenge. | Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence.,Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients.,However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.,The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.,C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce.,The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose.,Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation.,NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312.,Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.,BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure.,However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration.,The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation.,Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner.,Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.,Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD. | 1 |
Current guidelines recommend spirometry to confirm a diagnosis of chronic obstructive pulmonary disease (COPD).,To investigate whether a self-reported diagnosis of COPD is associated with prior spirometry and whether a correct diagnosis of COPD is more likely when spirometry was performed.,We used data from the population-based Austrian Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged >40 years and completed post-bronchodilator spirometry.,Reported COPD diagnosis and reported prior lung function test were based on questionnaire.,Persistent airflow limitation was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity ratio <0.7, corresponding with COPD Global initiative for chronic Obstructive Lung Disease (GOLD) grade I+, and GOLD grade II+ was also investigated.,A correct diagnosis of COPD was defined as a reported physician's diagnosis of COPD and the presence of persistent airflow limitation.,68 (5.4%) of 1,258 participants reported a prior physician's diagnosis of COPD.,Of these, only 17 (25.0%) reported a lung function test within the past 12 months and 46 (67.6%) at any time in the past.,The likelihood for a correct COPD GOLD grade I+ diagnosis was similar among subjects reporting a lung function test during the last 12 months (likelihood ratio 2.07, 95% CI 0.89 to 5.50) and those not reporting a lung function during the last 12 months (likelihood ratio 2.78, 95% CI 1.58 to 4.87).,Similar likelihood ratios were seen when GOLD grade II+ was investigated and when lung function was reported at any time in the past.,One-third of subjects with a reported diagnosis of COPD never had a lung function test.,When spirometry was reported, this did not increase the likelihood of a correct COPD diagnosis. | Underdiagnosis of chronic obstructive pulmonary disease (COPD) in primary care can be improved by a more efficient screening strategy.,To evaluate a three-step method of screening for COPD consisting of an initial short questionnaire followed by measurement of forced expiratory volume in 1s/forced expiratory volume in 6s (FEV1/FEV6) using an inexpensive pocket spirometer in those with high risk, and diagnostic quality spirometry in those with a low FEV1/FEV6.,We analysed two related Mexico City cross-sectional samples.,The 2003 Mexico City PLATINO survey (n=542) was used to develop a short questionnaire to determine the risk of COPD and a 2010 survey (n=737) additionally used a pocket spirometer.,The discriminatory power of the two instruments was assessed with receiver operator characteristic (ROC) curves using three COPD definitions.,The developed COPD scale included two variables from a simple questionnaire and, in ROC analysis, an area under the curve (AUC) between 0.64 and 0.77 was found to detect COPD.,The pocket spirometer had an AUC between 0.85 and 0.88 to detect COPD.,Using the COPD scale as a first screening step excluded 35-48% of the total population from further testing at the cost of not detecting 8-18% of those with COPD.,Using the pocket spirometer and sending those with a FEV1/FEV6<0.80 for diagnostic quality spirometry is very efficient, and substantially improved the positive predictive value at the cost of not detecting one-third of COPD cases.,A three-step screening strategy for COPD substantially reduces the need for spirometry testing when only a COPD scale is used for screening. | 1 |
Randomised, double-blind, controlled trials are considered the gold standard for evaluating a pharmacological agent, as they minimise any potential bias.,However, it is not always possible to perform double-blind trials, particularly for medications delivered via specific devices, e.g. inhalers.,In such cases, open-label studies can be employed instead.,Methods used to minimise any potential bias introduced by open-label study design include randomisation, crossover study design, and objective measurements of primary efficacy and safety variables.,Concise reviews analysing the effect of blinding procedures of comparator drugs on outcomes in respiratory trials are limited.,Here, we compare data from different chronic obstructive pulmonary disease trials with once-daily indacaterol versus a blinded or non-blinded comparator.,The clinical trial programme for indacaterol, a once-daily, long-acting β2-agonist, used tiotropium as a comparator either in an open-label or blinded fashion.,Data from these studies showed that the effects of tiotropium were consistent for forced expiratory volume in 1 second, an objective measure, across blinded and non-blinded studies.,The data were consistent with previous studies of double-blind tiotropium, suggesting that the open-label use of tiotropium did not introduce treatment bias.,The effect of tiotropium on subjective measures (St George’s Respiratory Questionnaire; transition dyspnoea index) varied slightly across blinded and non-blinded studies, indicating that minimal bias was introduced by using open-label tiotropium.,Importantly, the studies used randomised, open-label tiotropium patients to treatment allocation, a method shown to minimise bias to a greater degree than blinding.,In conclusion, it is important when reporting a clinical trial to be transparent about who was blinded and how the blinding was performed; if the design is open-label, additional efforts must be made to minimise risk of bias.,If these recommendations are followed, and the data are considered in the full knowledge of any potential sources of bias, results with tiotropium suggest that data from open-label studies can provide valuable and credible evidence of the effects of therapy. | Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD. | 1 |
To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score.,In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days.,A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL.,The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT.,We evaluated 40 COPD patients and 40 controls.,In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs.,105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs.,6.4 ± 3.2 km/day; p < 0.001).,The COPD patients also walked fewer steps/day.,The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower.,The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results.,Patients with COPD are less active than are healthy adults of a comparable age.,Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD.,However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD.,The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension.,The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension.,Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography.,Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension.,There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups.,For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels.,These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients. | 1 |
Bronchiectasis is prevalent in patients with COPD.,The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China.,Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed.,SPSS statistical software was used to analyze the data.,Data from 896 patients with COPD were analyzed.,Bronchiectasis was present in 311 patients.,The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35-6.37; P = 0.007).,During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group.,The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02-3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD.,These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum.,Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD. | COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function.,CT imaging is emerging as an important, noninvasive tool in phenotyping COPD.,However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known.,Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation.,Airway physiology and health status were also determined.,The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively.,The presence of EM was associated with lower lung function (mean difference % FEV1, −20%; 95% CI, −28 to −11; P < .001).,There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM.,The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96).,Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE.,The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD. | 1 |
Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | Eosinophilic COPD appears to be a distinct patient subgroup with an increased corticosteroid response.,Eosinophilic COPD has been labelled as part of the asthma COPD overlap syndrome (ACOS).,We compared the clinical characteristics of eosinophilic COPD patients (without any clinical history of asthma) and COPD patients with a childhood history of asthma.,COPD patients with asthma were characterised by more allergies and more exacerbations, but less eosinophilic inflammation.,While terms such as “ACOS” are used to “lump” patients together, we report distinct differences between eosinophilic COPD and COPD patients with asthma, and propose that these groups should be split rather than lumped. | 1 |
COPD is a progressive disease of the airways that is characterized by neutrophilic inflammation, a condition known to promote the excessive formation of neutrophil extracellular traps (NETs).,The presence of large amounts of NETs has recently been demonstrated for a variety of inflammatory lung diseases including cystic fibrosis, asthma and exacerbated COPD.,We test whether excessive NET generation is restricted to exacerbation of COPD or whether it also occurs during stable periods of the disease, and whether NET presence and amount correlates with the severity of airflow limitation.,Sputum samples from four study groups were examined: COPD patients during acute exacerbation, patients with stable disease, and smoking and non-smoking controls without airflow limitation.,Sputum induction followed the ECLIPSE protocol.,Confocal laser microscopy (CLSM) and electron microscopy were used to analyse samples.,Immunolabelling and fluorescent DNA staining were applied to trace NETs and related marker proteins.,CLSM specimens served for quantitative evaluation.,Sputum of COPD patients is clearly characterised by NETs and NET-forming neutrophils.,The presence of large amounts of NET is associated with disease severity (p < 0.001): over 90 % in exacerbated COPD, 45 % in stable COPD, and 25 % in smoking controls, but less than 5 % in non-smokers.,Quantification of NET-covered areas in sputum preparations confirms these results.,NET formation is not confined to exacerbation but also present in stable COPD and correlates with the severity of airflow limitation.,We infer that NETs are a major contributor to chronic inflammatory and lung tissue damage in COPD. | Patients with COPD have an increased risk of cardiovascular disease.,Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated.,We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.,Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment.,In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined.,These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.,On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar.,The IL-6 was also increased (p < 0.05).,Twenty-two patients completed study assessments.,In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01).,Total cholesterol and ISWT also improved (p < 0.05).,On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.,Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. | 1 |
COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors.,The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue.,Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found.,For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls.,Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction.,Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients.,For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated.,Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D.,Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups.,In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD.,The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment. | The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | 1 |
Symptom severity is the largest factor in determining subjective health in COPD.,Symptoms (eg, chronic cough, dyspnea) are associated with decreased health-related quality of life (HRQoL).,We evaluated the impact of arformoterol on HRQoL in COPD patients, measured by St George’s Respiratory Questionnaire (SGRQ).,Post hoc growth mixture model (GMM) analysis examined symptom response profiles.,We examined data from a randomized, double-blind, parallel-group, 12-month safety trial of twice-daily nebulized arformoterol 15 µg (n=420) versus placebo (n=421).,COPD severity was assessed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status.,GMM analysis identified previously unknown patient subgroups and examined the heterogeneity in response to SGRQ Symptoms scores.,SGRQ Total score improved by 4.24 points with arformoterol and 2.02 points with placebo (P=0.006).,Significantly greater improvements occurred for arformoterol versus placebo in SGRQ Symptoms (6.34 vs 4.25, P=0.031) and Impacts (3.91 vs 0.97, P=0.001) scores, but not in Activity score (3.57 vs 1.75, P=0.057).,GMM identified responders and nonresponders based on the SGRQ Symptoms score.,End-of-study mean difference in SGRQ Symptoms scores between these latent classes was 20.7 points (P<0.001; 95% confidence interval: 17.6-23.9).,Compared with nonresponders, responders were more likely current smokers (55.52% vs 44.02%, P=0.0021) and had more severe COPD (forced expiratory volume in 1 second [FEV1]: 1.16 vs 1.23 L, P=0.0419), more exacerbations (0.96 vs 0.69, P=0.0018), and worse mean SGRQ Total (59.81 vs 40.57, P<0.0001), Clinical COPD Questionnaire (3.29 vs 2.05, P<0.0001), and Modified Medical Research Council Dyspnea Scale (3.13 vs 2.75, P<0.0001) scores.,Arformoterol-receiving responders exhibited significantly greater improvements in FEV1 (0.09 vs 0.008, P=0.03) and fewer hospitalizations (0.13 vs 0.24, P=0.02) than those receiving placebo.,In this study, arformoterol treatment significantly improved HRQoL reflected by SGRQ.,For the analysis performed on these data, arformoterol may be particularly effective in improving lung function and reducing hospitalizations among patients who are unable to quit smoking or present with more severe symptoms. | Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team. | 1 |
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies.,Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking.,Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions.,Exosomal miRNAs have been studied in relation to many diseases.,However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF.,Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts.,Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration.,Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL.,NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers.,Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively.,Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls.,Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets. | Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity.,The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers.,Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction.,We compared total EMPs (CD31+CD42b-), apoptotic if they co-expressed Annexin-V+ or activated if they co-expressed CD62E+, circulating PCs (CD34+CD133+CD45+) and the EMPs/PCs ratio between groups.,COPD patients presented increased levels of total and apoptotic circulating EMPs, and an increased EMPs/PCs ratio, compared with nonsmokers.,Women had less circulating PCs than men through all groups and those with COPD showed lower levels of PCs than both control groups.,In smokers, circulating EMPs and PCs did not differ from nonsmokers, being the EMPs/PCs ratio in an intermediate position between COPD and nonsmokers.,We conclude that COPD patients present an imbalance between endothelial damage and repair capacity that might explain the frequent concurrence of cardiovascular disorders.,Factors related to the disease itself and gender, rather than cigarette smoking, may account for this imbalance. | 1 |
COPD prevalence is highly variable and geographical altitude has been linked to it, yet with conflicting results.,We aimed to investigate this association, considering well known risk factors.,A pooled analysis of individual data from the PREPOCOL-PLATINO-BOLD-EPI-SCAN studies was used to disentangle the population effect of geographical altitude on COPD prevalence.,Post-bronchodilator FEV1/FVC below the lower limit of normal defined airflow limitation consistent with COPD.,High altitude was defined as >1500 m above sea level.,Undiagnosed COPD was considered when participants had airflow limitation but did not report a prior diagnosis of COPD.,Among 30,874 participants aged 56.1 ± 11.3 years from 44 sites worldwide, 55.8% were women, 49.6% never-smokers, and 12.9% (3978 subjects) were residing above 1500 m.,COPD prevalence was significantly lower in participants living at high altitude with a prevalence of 8.5% compared to 9.9%, respectively (p < 0.005).,However, known risk factors were significantly less frequent at high altitude.,Hence, in the adjusted multivariate analysis, altitude itself had no significant influence on COPD prevalence.,Living at high altitude, however, was associated with a significantly increased risk of undiagnosed COPD.,Furthermore, subjects with airflow limitation living at high altitude reported significantly less respiratory symptoms compared to subjects residing at lower altitude.,Living at high altitude is not associated with a difference in COPD prevalence after accounting for individual risk factors.,However, high altitude itself was associated with an increased risk of undiagnosed COPD. | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung and whole body caused mainly by tobacco smoking.,Patients with advanced COPD are in a state of undernutrition, referred to as pulmonary cachexia; the exercise performance and quality of life (QOL) of these patients are deteriorated, the vital prognosis is unfavorable, and the medico-economic burden posed by poorly nourished COPD patients is high.,The mainstays of COPD treatment are pharmacotherapy, mainly with bronchodilators, and non-pharmacotherapeutic approaches such as respiratory rehabilitation and nutrition counseling.,Nutritional supplement therapy, consisting primarily of high calorie intake, has been demonstrated to be effective for maintaining and improving the muscle strength and exercise tolerance in poorly nourished COPD patients.,The efficacy of intake of various nutrients, besides a high calorie intake, for amelioration of the disease state of COPD has also been reported.,The roles of adipokines in the pathophysiology of COPD have begun to receive attention recently, and not only their regulatory effects on appetite and nutritional status, but also their influence on systemic inflammation have been increasingly clarified.,We review the papers on COPD and nutrition and discuss the role of nutritional supplement therapy in the treatment of COPD. | 1 |
Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting.,We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients.,We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016.,Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included.,Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25-1.07].,Eosinophilia was associated with reduced length of hospital stay (P = 0.04).,Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05-3.23, P < 0.001].,Inclusion of hospitalized patients nullified the effect.,Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of hospitalization status.,In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes. | 1 |
A year-long pan-Canadian quality improvement collaborative (QIC) led by the Canadian Foundation for Healthcare Improvement (CFHI) supported the spread of the successful Halifax, Nova Scotia-based INSPIRED COPD Outreach Program™ to 19 teams in the 10 Canadian provinces.,We describe QIC results, addressing two main questions: 1) Can the results of the Nova Scotia INSPIRED model be replicated elsewhere in Canada?,2) How did the teams implement and evaluate their versions of the INSPIRED program?,Collaborative faculty selected measures that were evidence-based, relatively simple to collect, and relevant to local context.,Chosen process and outcome measures are related to four quality domains: 1) patient- and family-centeredness, 2) coordination, 3) efficiency, and 4) appropriateness.,Evaluation of a complex intervention followed a mixed-methods approach.,Most participants were nurse managers and/or COPD educators.,Only 8% were physicians.,Fifteen teams incorporated all core INSPIRED interventions.,All teams carried out evaluation.,Thirteen teams actively involved patients and families in customized, direct care planning, eg, asking them to complete evaluative surveys and/or conducting interviews.,Patients consistently reported greater self-confidence in symptom management, a return to daily activities, and improvements to quality of life.,Twelve teams collected data on care transitions using the validated three-item Care Transitions Measure (CTM-3).,Twelve teams used the Lung Information Needs Questionnaire (LINQ).,Admissions, emergency room visits, and patient-related costs fell substantially for two teams described in detail (combined enrollment 208 patients).,Most teams reported gaining deeper knowledge around complexities of COPD care, optimizing patient care through action plans, self-management support, psychosocial support, advance care planning, and coordinating community partnerships.,Quality-of-care gains are achievable in the short term among different teams across diverse geographical and social contexts.,A well-designed, adequately funded public-private partnership can deliver widespread beneficial outcomes for the health care system and for those living with advanced COPD. | Chronic obstructive pulmonary disease and lung cancer are leading causes of death with comparable symptoms at the end of life.,Cross-national comparisons of place of death, as an important outcome of terminal care, between people dying from chronic obstructive pulmonary disease and lung cancer have not been studied before.,We collected population death certificate data from 14 countries (year: 2008), covering place of death, underlying cause of death, and demographic information.,We included patients dying from lung cancer or chronic obstructive pulmonary disease and used descriptive statistics and multivariable logistic regressions to describe patterns in place of death.,Of 5,568,827 deaths, 5.8% were from lung cancer and 4.4% from chronic obstructive pulmonary disease.,Among lung cancer decedents, home deaths ranged from 12.5% in South Korea to 57.1% in Mexico, while hospital deaths ranged from 27.5% in New Zealand to 77.4% in France.,In chronic obstructive pulmonary disease patients, the proportion dying at home ranged from 10.4% in Canada to 55.4% in Mexico, while hospital deaths ranged from 41.8% in Mexico to 78.9% in South Korea.,Controlling for age, sex, and marital status, patients with chronic obstructive pulmonary disease were significantly less likely die at home rather than in hospital in nine countries.,Our study found in almost all countries that those dying from chronic obstructive pulmonary disease as compared with those from lung cancer are less likely to die at home and at a palliative care institution and more likely to die in a hospital or a nursing home.,This might be due to less predictable disease trajectories and prognosis of death in chronic obstructive pulmonary disease.,Structured palliative care similar to that offered to cancer sufferers should be in place for patients with chronic lung disease.,Joachim Cohen at Vrije University in Brussels and co-workers examined international death certificate data collected from 14 countries to determine place of death for patients with lung cancer and chronic obstructive pulmonary disease (COPD).,While patients with COPD suffer similar symptoms to lung cancer in their final days, few COPD patients receive palliative care or achieve the common wish of dying at home.,This may be partly due to the inherent unpredictability of final-stage COPD compared with lung cancer.,Cohen’s team found that, with the exception of Italy, Spain, and Mexico, patients with COPD were significantly more likely to die in hospital than at home.,They highlight the need for improved COPD palliative care provision. | 1 |
Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS).,Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function.,In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity.,In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression.,In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit.,This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases. | There is a need to identify individuals with COPD at risk for disease progression and mortality.,Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation.,We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling.,Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort.,Validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used.,Multivariate models were used to assess the prognostic value of these biomarkers.,Thirty subjects (3.0 %) died during follow-up.,Non-survivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers.,All collagen biomarkers were significantly elevated in non-survivors compared to survivors.,Mortality risk was significantly increased for subjects with collagen remodeling biomarkers in the upper quartile, especially for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 % confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant confounders.,Serological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD.,NCT00292552, GSK Study No.,SCO104960.,The online version of this article (doi:10.1186/s12931-016-0440-6) contains supplementary material, which is available to authorized users. | 1 |
A new phenotype with overlapping characteristics between asthma and chronic obstructive pulmonary disease (COPD) called asthma-COPD overlap syndrome (ACOS) is emerging among inflammation diseases.,To date, there is no agreement on specific criteria to define this syndrome, and the current guidelines are insufficient to classify the analogy and differences between overlap and COPD or asthma phenotypes.,It would be necessary to identify new biomarkers able to identify these diseases clearly.,Thus, the aim of this study was to identify a serum and supernatant of sputum microRNA (miRNA) expression profile of miRNA-145 and miRNA-338 in patients with asthma (n=13), COPD (n=31), and ACOS (n=8) and controls (n=7).,The expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).,For statistical analysis, the ANOVA test, Kruskal-Wallis test, Mann-Whitney U-test, and Spearman’s rank correlation were used.,The main finding of this work is that the expression of miRNA-338 is higher in the supernatant of different obstructive diseases than in peripheral blood, while miRNA-145 is higher only in the supernatant of asthma patients.,The expression of both selected miRNAs is higher in the supernatant of asthma and COPD patients than in controls.,Differences in sputum miRNA expression profile were observed between patients with ACOS and asthma or COPD, which underline the potential role of miRNA as a biomarker that is able to discriminate patients with ACOS, asthma, and COPD. | COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors.,The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue.,Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found.,For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls.,Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction.,Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients.,For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated.,Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D.,Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups.,In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD.,The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment. | 1 |
The goal of this manuscript is to explore the role of clinical proteomics for detecting mutations in chronic obstructive pulmonary disease (COPD) and lung cancer by mass spectrometry‐based technology.,COPD and lung cancer caused by smoke inhalation are most likely linked by challenging the immune system via partly shared pathways.,Genome‐wide association studies have identified several single nucleotide polymorphisms which predispose an increased susceptibility to COPD and lung cancer.,In lung cancer, this leads to coding mutations in the affected tissues, development of neoantigens, and different functionality and abundance of proteins in specific pathways.,If a similar reasoning can also be applied in COPD will be discussed.,The technology of mass spectrometry has developed into an advanced technology for proteome research detecting mutated peptides or proteins and finding relevant molecular mechanisms that will enable predicting the response to immunotherapy in COPD and lung cancer patients. | There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD.,B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients.,Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions.,We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens).,Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.,The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.,COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells.,Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.,This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung.,The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells.,Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD. | 1 |
COPD is a treatable disease with increasing prevalence worldwide.,Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations.,We aimed to evaluate the association of the stage of COPD on adherence to inhaled therapy and the relationship between adherence and COPD exacerbations.,A retrospective analysis of patients hospitalized for acute exacerbation of COPD in a tertiary care hospital in Upper Austria and discharged with a guideline conform inhaled therapy was performed.,Follow-up data on medical utilization was recorded for the subsequent 24 months.,Adherence to inhaled therapy was defined according to the percentage of prescribed inhalers dispensed to the patient and classified as complete (> 80%), partial (50-80%) or low (< 50%).,Out of 357 patients, 65.8% were male with a mean age of 66.5 years and a mean FEV1 of 55.0%pred.,Overall, 35.3% were current smokers, and only 3.9% were never-smokers.,In 77.0% inhaled triple therapy (LAMA + LABA + ICS) was prescribed.,33.6% showed complete adherence to their therapy (33.2% in men, 34.4% in women), with a mean age of 67.0 years.,Mean medication possession ratio by GOLD spirometry class I - IV were 0.486, 0.534, 0.609 and 0.755, respectively (p = 0.002).,Hence, subjects with complete adherence to therapy had a significantly lower FEV1 compared to those with low adherence (49.2%pred. vs 59.2%pred., respectively; p < 0.001).,The risk of exacerbations leading to hospitalization was 10-fold higher in GOLD spirometry class IV compared to GOLD spirometry class I, which was even more evident in multivariate analysis (OR 13.62).,Complete adherence to inhaled therapy was only seen in 33.6% and was higher among those with more severe COPD.,Not applicable. | Background: To validate the ‘Test of Adherence to Inhalers’ (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma.,Methods: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study.,Patients with electronic adherence ≥80% were defined as adherents.,Construct validity, internal validity, and criterion validity were evaluated.,Self-reported adherence was compared with the Morisky-Green questionnaire.,Results: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12).,The Cronbach's alpha was 0.860 and the test-retest reliability 0.883.,TAI scores correlated with electronic adherence (ρ=0.293, p=0.01).,According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents.,The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients.,As compared to Morisky-Green test, TAI showed better psychometric properties.,Conclusions: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD. | 1 |
Dual bronchodilator maintenance therapy may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) versus long-acting muscarinic antagonist (LAMA) monotherapy.,The efficacy and safety of US-approved LAMA/long-acting beta-agonist (LABA) combinations versus tiotropium (TIO), a LAMA, were assessed.,This systematic review and meta-analysis (GSK: 206938), conducted in MEDLINE, MEDLINE In-process, and EMBASE following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, identified randomized clinical trials (>8 weeks) in moderate-to-severe COPD (per Global Initiative for Chronic Obstructive Lung Disease guidelines), receiving LAMA/LABA or TIO.,Endpoints: difference in change from baseline in lung function (forced expiratory volume in 1 s [FEV1]; trough, peak, area under the curve 0-3 h post-dose (AUC0-3), St George’s Respiratory Questionnaire (SGRQ) responder rate (≥4-unit improvement), SGRQ total score, and rescue medication use at 12 and 24 weeks.,Safety was also assessed.,From 5683 citations, the meta-analysis included eight clinical trials.,LAMA/LABA significantly improved FEV1 trough (Week 12: 63.0 mL, 95% confidence intervals [CI]: 39.2, 86.8; Week 24: 66.1 mL, 95% CI: 40.0, 92.3), peak (Week 12: 91.5 mL, 95% CI: 70.5, 112.4; Week 24: 92.4 mL, 95% CI: 72.9, 111.9), AUC0-3 (Week 12: 126.8 mL, 95% CI: 108.1, 145.4), SGRQ responder rate at Week 12 (risk ratio: 1.19; 95% CI: 1.09, 1.28), mean SGRQ total score (Week 12: −1.87, 95% CI: −2.72, −1.02; Week 24: −1.05, 95% CI: −2.02, −0.09), and rescue medication use (Week 24: −0.47 puffs/day, 95% CI: −0.64, −0.30) versus TIO (all p ≤ 0.03).,The SGRQ responder rate at 24 weeks and adverse events were not significantly different between treatments.,US-approved LAMA/LABA therapies improved lung function, SGR,Q and rescue medication use versus TIO, without compromising safety.,Dual maintenance therapies combining two types of long-acting bronchodilator appear to be effective and safe for treating moderate-to-severe chronic obstructive pulmonary disease (COPD).,Given that patients with COPD often have poor quality of life and, in the US, incur substantial healthcare costs, it is vital to provide optimal symptom management to improve lung function and limit exacerbations over time.,Beth Hahn at GSK, North Carolina, and co-workers carried out a literature review and meta-analysis of 8 clinical trials, which indicates that combined long-acting muscarinic antagonist (LAMA)/long-acting beta-agonist (LABA) treatments-currently prescribed in the US-are an effective and safe way of tackling COPD symptoms.,The team compared patients using LAMA/LABA for 12 weeks with those on single LAMA (tiotropium) treatment and found LAMA/LABA significantly improved lung function and reduced exacerbation risk. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and it has become a major public health burden worldwide, including in Vietnam.,A large body of preclinical and clinical studies supports the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of lung injury, including COPD.,The aim of this trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in combination with standard COPD medication treatments in patients with moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam Ministry of Health’s guidelines.,This matched case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June 2020 and December 2021.,In this study, 40 patients will be enrolled and assigned into two age-matched, gender-matched and COPD condition-matched groups, including a UC-MSC group and a control group.,Both groups will receive standard COPD medication treatment based on the GOLD 2019 guidelines and the Vietnam Ministry of Health protocol.,The UC-MSC group will receive two doses of thawed UC-MSC product with an intervention interval of 3 months.,The primary outcome measures will include the incidence of prespecified administration-associated adverse events and serious adverse events.,The efficacy will be evaluated based on the absolute changes in the number of admissions, arterial blood gas analysis, lung function and lung fibrosis via CT scan and chest X-ray.,The clinical evaluation will be conducted at baseline and 3, 6 and 12 months postintervention.,Ethical approval was secured from the Ethical Committee of Vinmec International Hospital (number:166/2019/QĐ-VMEC) and Vietnam Ministry of Health (number:2002/QĐ-BYT).,The results will be reported to trial collaborators, publication in peer-reviewed academic journals.,NCT04433104. | One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients.,However, local inflammation may result and can contribute to worsening of clinical status in these patients.,We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients.,This initial study sought to investigate the safety of this approach.,For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used.,Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs.,Patients were evaluated 1, 7, 30, and 90 days after therapy.,All patients completed the study protocol and 90‐day follow‐up.,MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death.,No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease.,Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes.,However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV.,EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores.,Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy.,Stem Cells Translational Medicine 2017;6:962-969 | 1 |
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | 1 |
We investigated patients with chronic obstructive pulmonary disease (COPD) to analyze patterns and identify determinants of healthcare use, according to the severity of airflow obstruction.,We used retrospective cohort data from a combination of the 4th Korea National Health and Nutritional Examination Survey (KNHANES) and Korean National Health Insurance (NHI) claims.,Demographic and medical claims data were retrospectively analyzed from the 4th KNHANES along with NHI claims.,Eligible patients were aged ≥40 years, who underwent complete pulmonary function tests (PFTs), and had at least one inpatient or outpatient claim coded as COPD between January 1, 2007 and December 31, 2010.,Among 6,663 eligible participants, 897 (13.5%) had airway obstruction.,Self-reported physician-diagnosed COPD comprised only 3%, and there were 870 undiagnosed COPD patients (97%).,Self-reported physician-diagnosed asthma made up 3.7%.,Of the 897 respondents, 244 (27.2%) used COPD-related healthcare services.,The frequency of healthcare visits increased with increasing severity of airway obstruction.,After a 3-year follow-up period, 646 (74.2% of those initially undiagnosed) remained undiagnosed and only 224 (25.8%) were diagnosed and treated for COPD.,Only 27.5% of the 244 participants with airway obstruction who used COPD-related healthcare underwent PFTs during the study period.,The percentage of prescribed medications associated with COPD increased in accordance with the severity of the COPD.,Inhaled long-acting anticholinergics were prescribed for 10.9% of patients with moderate airway obstruction and for 52.4% of patients with severe obstruction.,Inhaled long-acting β-agonists combined with corticosteroids were prescribed for 50% of patients with severe airway obstruction.,Conversely, 44.6% of healthcare users were prescribed oral theophylline for COPD treatment, and 21.7% were also prescribed an oral corticosteroid.,The determinants of COPD-associated healthcare use in respondents with obstructive lung disease were advanced age, severe airflow limitation, presence of comorbidities, and self-reported physician diagnosis of COPD.,This study ascertained marked underdiagnosed COPD.,Although the percentage of prescribed medication used to treat COPD increased with the severity of the COPD, medications primarily prescribed such as oral theophylline or oral corticosteroids are inappropriate for first-line COPD treatment. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.,Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan.,Patients were grouped according to GOLD 2011 and 2017 guidelines respectively.,Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.,A total of 1,053 COPD patients were included.,The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively.,When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively.,Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B.,The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017.,Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017.,The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.,The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011.,A pharmacological discordance to the guidelines was identified.,Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines.,Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function and poor outcomes for patients.,However, there are limited data on the time course of changes in forced expiratory volume in 1 s (FEV1) preceding the first reported symptom and after the start of an exacerbation.,WISDOM was a multinational, randomized, double-blind, active-controlled, 52-week study in patients with severe-to-very severe COPD.,Patients received triple therapy (long-acting muscarinic antagonist and long-acting β2-agonist/inhaled corticosteroid [ICS]) for 6 weeks, and were randomized to continue triple therapy or stepwise withdrawal of the ICS (dual bronchodilator group).,After suitable training, patients performed daily spirometry at home using a portable, battery-operated spirometer.,In the present post hoc analysis, patients who continued to perform daily home spirometry and completed at least one measurement per week for a 56-day period before and after the start of a moderate or severe exacerbation were included.,Missing values were imputed by linear interpolation (intermittent), backfilling (beginning) or carry forward (end).,Exacerbation onset was the first day of a reported symptom of exacerbation.,Eight hundred and eighty-eight patients in the WISDOM study had a moderate/severe exacerbation after the complete ICS withdrawal visit; 360 of them contributed at least one FEV1 measure per week for the 8 weeks before and after the event and are included in this analysis.,Mean daily FEV1 began to decline from approximately 2 weeks before the onset of symptoms of an exacerbation, dropping from 0.907 L (mean Days − 56 to − 36 before the exacerbation) to 0.860 L on the first day of the exacerbation.,After the exacerbation, mean FEV1 improved but did not return to pre-exacerbation levels (mean Days 36-56 after the exacerbation, 0.875 L).,The pattern of FEV1 changes around exacerbations was similar in the triple therapy and dual bronchodilator groups, and a similar pattern was seen in moderate and severe exacerbations when analysed separately.,Mean lung function starts to decline prior to the first reported symptoms of an exacerbation, and does not recover to pre-exacerbation levels 8 weeks after the event.,WISDOM (ClinicalTrials.gov number, NCT00975195).,The online version of this article (10.1186/s12931-018-0944-3) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice.,The aim of this study was to explore the factors associated with the use of ICS in these patients.,The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan.,Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients.,Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively).,The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients.,Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14-4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24-2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40-2.96; P<0.001).,The COPD assessment test score was also associated with an ICS prescription in group B (OR, 1.04; 95% CI, 1.00-1.07; P=0.038).,About one-third of the GOLD group A and B patients with COPD in Taiwan are prescribed ICS.,Our findings suggest that wheezing and COPD assessment test score are related to the prescription of ICS in these patients. | Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | 1 |
Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease (COPD).,This randomised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD.,Eighty patients (66±7 years, 81% male, forced expiratory volume in 1 second 45±16% of predicted) referred for a six‐month multidisciplinary pulmonary rehabilitation program were randomised.,The intervention group was offered an additional eight-session activity counselling program.,The primary outcomes were daily walking time and time spent in at least moderate intense activities.,Baseline daily walking time was similar in the intervention and control group (median 33 [interquartile range 16-47] vs 29 [17-44]) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group (17[4-50] vs 12[2-26] min).,No significant intervention*time interaction effects were observed in daily physical activity levels.,In the whole group, daily walking time and time spent in at least moderate intense activities did not significantly change over time.,The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD.,clinicaltrials.gov NCT00948623 | Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 1 |
Glycopyrronium bromide (NVA237) is an inhaled long-acting muscarinic antagonist in development for treatment of COPD.,This study compared the efficacy and safety of once-daily (OD) and twice-daily (BID) glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD.,Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design.,Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and <80% predicted, FEV1/FVC <0.7) were randomized to one of 16 independent sequences for 28 days.,Primary endpoint: mean trough FEV1 at Day 28.,385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted) were randomized; 88.6% completed.,All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD) to 160 mL (glycopyrronium bromide 50 μg BID).,Pharmacodynamic steady-state was reached by Day 7.,There was a small separation (≤37 mL) between BID and OD dose-response curves for mean trough FEV1 at steady-state in favour of BID dosing.,Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL).,Dose-response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12-24 hours.,The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL).,Glycopyrronium bromide was safe and well tolerated at all doses.,Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period, and in terms of FEV1 AUC0-24h is not significantly different than the same total daily dose administered BID.,Importantly, OD dosing may confer better patient adherence.,The results are consistent with previous glycopyrronium bromide studies and support once-daily dosing of glycopyrronium bromide 50 μg in patients with moderate-to-severe COPD.,ClinicalTrials.gov: NCT01119950 | NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901 | 1 |
Chronic obstructive pulmonary disease (COPD) patients present a high prevalence of cardiovascular disease.,This excess of comorbidity could be related to a common pathogenic mechanism, but it could also be explained by the existence of common risk factors.,The objective of this study was to determine whether COPD patients present greater cardiovascular comorbidity than control subjects and whether COPD can be considered a risk factor per se.,1200 COPD patients and 300 control subjects were recruited for this multicenter, cross-sectional, case-control study.,Compared with the control group, the COPD group showed a significantly higher prevalence of ischemic heart disease (12.5% versus 4.7%; P < 0.0001), cerebrovascular disease (10% versus 2%; P < 0.0001), and peripheral vascular disease (16.4% versus 4.1%; P < 0.001).,In the univariate risk analysis, COPD, hypertension, diabetes, obesity, and dyslipidemia were risk factors for ischemic heart disease.,In the multivariate analysis adjusted for the remaining factors, COPD was still an independent risk factor (odds ratio: 2.23; 95% confidence interval: 1.18-4.24; P = 0.014).,COPD patients show a high prevalence of cardiovascular disease, higher than expected given their age and the coexistence of classic cardiovascular risk factors. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
COPD is one of the leading causes of morbidity and mortality in the world; however, the most varied amounts of clinical and laboratory characteristics acts in different ways in the mortality among over time.,Therefore, this study aimed to evaluate the predictors of mortality in patients with COPD after 9 years.,One hundred and thirty-three patients with COPD were assessed at baseline by spirometry, pulse oximetry (SpO2), body composition, intensity of dyspnea, distance walked in the 6-minute walk test (6MWT), and Charlson Comorbidity Index (CCI).,After 9 years, it was not possible to identify the lifetime of 4 patients who died and of 19 patients who stopped follow-up; thus, 110 patients were included in the analysis of predictors of mortality (67% male, 65±9 years old, and FEV1: 52.5 [40%-73%]).,Male sex, age, SpO2, Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index, and frequency of exacerbations in the first 3 years of follow-up were considered in the model.,Patients classified at baseline with BODE class 2 (HR: 2.62, 95% CI: 1.36-5.04; P=0.004), BODE class 3 (HR: 2.54, 95% CI: 1.15-5.61; P=0.02), and BODE class 4 (HR: 15.35, 95% CI: 3.11-75.75; P=0.001) showed increased risk of death compared to those with BODE class 1.,The CCI (HR: 1.29, 95% CI: 1.00-1.68; P=0.04) and the number of exacerbations in the first 3 years (HR: 1.32, 95% CI: 1.00-1.76; P=0.04) also showed increased risk of death.,By replacing the BODE index for the variables that compose it, those with body mass index ≤21 kg/m2 showed increased risk of death compared to those with body mass index (BMI)>21 kg/m2 (HR: 2.70, 95% CI: 1.38-5.25; P=0.003).,After 9 years, we identified that those with high BODE index, greater CCI, greater frequency of exacerbations in the first 3 years, and BMI ≤21 kg/m2 showed increased risk of death. | Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories.,The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients.,This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland.,The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices.,DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations.,Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items.,The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups.,The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them.,None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality.,The GOLD categories predict future risk inconsistently.,The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. | 1 |
The beneficial effects of physical activity (PA) in patients with COPD, as well as the methods of their assessment, are well known and described.,As objective measures of PA, such as the use of motion sensors, video recordings, exercise capacity testing, and indirect calorimetry, are not easily obtained in the daily clinical life, the reliability of the more accessible self-reported measurements of PA is important.,In this review, we systematically identified original studies involving COPD patients and at least one parameter of self-reported and objective exercise testing, and analyzed every article for coherence between the objectively and self-reported measured PA.,The studies are few, small, and very diverse, both in their use of questionnaires and objective measurements.,Self-reported assessments were found to generally overestimate the level of PA compared to measurements made objectively by activity monitors; however, more studies are needed to rely solely on the use of PA questionnaires in COPD patients.,The most accurate and valid questionnaires appear to be the self-completed Physical Activity Scale for the Elderly and the interviewer-completed Stanford Seven-Day Physical Activity Recall Questionnaire, but the ideal questionnaire still awaits construction.,The motion sensors are accurate and validated in this patient group, especially SenseWear™, but not easily accessible in clinical practice, as they have various technical and adhesive difficulties. | Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | 1 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD).,The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.,A systematic search of electronic databases was performed.,Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3).,The pooled Hedges’s g with 95% confidence intervals (95% CIs) was adopted to assess the effect size.,Random effect model was used due to the heterogeneity between the studies.,A total of 20 eligible studies were included in the current systematic review.,The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges’s g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges’s g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges’s g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges’s g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001).,The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges’s g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges’s g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001).,This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment.,Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD.,The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair. | Although both animal and human studies suggested the association between placenta growth factor (PlGF) and chronic obstructive pulmonary disease (COPD), especially lung emphysema, the role of PlGF in the pathogenesis of emphysema remains to be clarified.,This study hypothesizes that blocking PlGF prevents the development of emphysema.,Pulmonary emphysema was induced in PlGF knock-out (KO) and wild type (WT) mice by intra-tracheal instillation of porcine pancreatic elastase (PPE).,A group of KO mice was then treated with exogenous PlGF and WT mice with neutralizing anti-VEGFR1 antibody.,Tumor necrosis factor alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), and VEGF were quantified.,Apoptosis measurement and immuno-histochemical staining for VEGF R1 and R2 were performed in emphysematous lung tissues.,After 4 weeks of PPE instillation, lung airspaces enlarged more significantly in WT than in KO mice.,The levels of TNF-α and MMP-9, but not VEGF, increased in the lungs of WT compared with those of KO mice.,There was also increased in apoptosis of alveolar septal cells in WT mice.,Instillation of exogenous PlGF in KO mice restored the emphysematous changes.,The expression of both VEGF R1 and R2 decreased in the emphysematous lungs.,In this animal model, pulmonary emphysema is prevented by depleting PlGF.,When exogenous PlGF is administered to PlGF KO mice, emphysema re-develops, implying that PlGF contributes to the pathogenesis of emphysema. | 1 |
A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions.,To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending.,A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD).,Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants.,Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier.,In addition, we identified determinants associated with low activation for self-management using logistic regression analysis.,We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients.,Mean age was 69.6±10.9.,Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%.,All associations, except for social support, were disease transcending.,This study explored factors associated with varying levels of activation for self-management.,These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management.,Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management. | If patients are to participate fully in their care and in the management of a long term condition such as chronic obstructive pulmonary disease, good communication is essential.,However, not all patients are able to use the written word and we need to be aware of the size of this problem and its implications for the way in which we give information and conduct medical consultations.,The impact of health literacy on outcomes can be considerable and improvements can be made by being aware of the problem, offering information in several different forms, and by reinforcing the spoken word with pictorial images. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD), though the mechanisms of its toxicity are still unclear.,The ABC transporters multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp/MDR1) extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium.,Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke.,We examined whether triple knock-out (TKO) mice lacking the genes for Mrp1 and Mdr1a/1b are more susceptible to develop COPD features than their wild-type (WT) littermates.,TKO and WT mice (six per group) were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months.,Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept.,Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences.,TKO mice had lower levels of interleukin (IL)-7, KC (mouse IL-8), IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (P < 0.05).,IL-1-alpha, IL-6, IL-8, IL-13, IL-17, TNF-alpha, G-CSF, GM-CSF and MCP-1 increased after smoke exposure in both groups, but the increase in IL-8 was lower in TKO than WT mice (P < 0.05) with a same trend for G-CSF (P < 0.10).,Smoke-induced increase in pulmonary inflammatory cells in WT mice was almost absent in TKO mice.,The mean linear intercept was not different between groups.,Mrp1/Mdr1a/1b knock-out mice have a reduced inflammatory response to cigarette smoke.,In addition, the expression levels of several cytokines and chemokines were also lower in lungs of Mrp1/Mdr1a/1b knock-out mice independent of smoke exposure.,Further studies are required to determine whether dysfunction of MRP1 and/or P-gp contribute to the pathogenesis of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality.,COPD is typified by persistent, progressive airflow limitation and a range of respiratory and systemic symptoms such as breathlessness, coughing, wheezing, depression, anxiety, general fatigue, and sleeping difficulties.,Despite receiving treatment for COPD, many patients suffer from regular symptoms that affect their daily lives and lead to increased morbidity.,These symptoms vary in severity, frequency, and type, and can occur at any time throughout the 24-h day, with over half of patients with COPD experiencing symptoms in the morning, during the day, and at nighttime.,Despite the prevalence of symptoms, patient and physician perception of the impact of COPD symptoms on patients’ lives is not always in concordance.,Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and long-acting beta agonist (LABA) has the potential to treat the symptoms of COPD in addition to improving lung function.,This review therefore examines the burden of symptoms experienced throughout the day by patients with COPD and the evidence for combined LAMA/LABA treatment in terms of symptom management.,As patients with COPD experience varying symptoms throughout the course of their disease, the role of tailoring treatment to the individual needs of the patient is also examined.,We conclude that the symptoms of COPD are troublesome, variable, can occur during all parts of the 24-h day, and have a substantial impact on patients’ health status and quality of life.,In order to provide effective, patient-orientated care, patients with COPD should be evaluated on the basis of lung function, the frequency of symptoms, and patient-perceived impact of symptoms on their lives.,Therapy should be chosen carefully based on individualized assessment, ensuring personalization to the individual needs of the patient. | Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | 1 |
This study assessed the adherence profiles to inhaled therapies and the agreement between two patient self-report adherence methods in stable COPD lpatients from seven Latin American countries.,This observational, cross-sectional, multinational, multicenter study involved 795 COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] <0.70).,Adherence to inhaled therapy was assessed using the specific Test of Adherence to Inhalers (10-item TAI) and the generic 8-item Morisky Medication Adherence Scale (MMAS-8) questionnaires.,The percentage agreement and the kappa index were used to compare findings.,59.6% of patients were male (69.5±8.7 years); post-bronchodilator FEV1 percent predicted was 50.0±18.6%.,Mean values for 10-item TAI and MMAS-8 questionnaires were 47.4±4.9 and 6.8±1.6, respectively.,Based on the TAI questionnaire, 54.1% of patients had good, 26.5% intermediate, and 19.4% poor adherence.,Using the MMAS-8 questionnaire, 51% had high, 29.1% medium, and 19.9% low adherence.,According to both questionnaires, patients with poor adherence had lower smoking history, schooling but higher COPD Assessment Test score, exacerbations in the past-year and post-bronchodilator FEV1.,The agreement between 10-item TAI and MMAS-8 questionnaires was moderate (Kappa index: 0.42; agreement: 64.7%).,Suboptimal adherence to medication was frequent in COPD patients from Latin America.,Low adherence was associated with worse health status impairment and more exacerbations.,There was inadequate agreement between the two questionnaires.,Greater effort should be made to improve COPD patients’ adherence to treatment, and assessment of adherence with more specific instruments, such as the TAI questionnaire, would be more convenient in these patients.,NCT02789540 | Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF).,The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD).,The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation.,This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50).,Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device.,After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups).,After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients.,After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler.,All patients achieved PIF values of at least 30 L/min after enhanced training.,The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar.,The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use.,After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery.,Enhanced training could be useful, especially in COPD patients. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | 1 |
There is insufficient evidence of the cost-effectiveness of Chronic Obstructive Pulmonary Disease (COPD) Disease Management (COPD-DM) programs.,The aim of this review is to evaluate the economic impact of COPD-DM programs and investigate the relation between the impact on healthcare costs and health outcomes.,We also investigated the impact of patient-, intervention, and study-characteristics.,We conducted a systematic literature review to identify cost-effectiveness studies of COPD-DM.,Where feasible, results were pooled using random-effects meta-analysis and explorative subgroup analyses were performed.,Sixteen papers describing 11 studies were included (7 randomized control trials (RCT), 2 pre-post, 2 case-control).,Meta-analysis showed that COPD-DM led to hospitalization savings of €1060 (95% CI: €2040 to €80) per patient per year and savings in total healthcare utilization of €898 (95% CI: €1566 to €231) (excl. operating costs).,In these health economic studies small but positive results on health outcomes were found, such as the St Georges Respiratory Questionnaire (SGRQ) score, which decreased with 1.7 points (95% CI: 0.5-2.9).,There was great variability in DM interventions-, study- and patient-characteristics.,There were indications that DM showed greater savings in studies with: severe COPD patients, patients with a history of exacerbations, RCT study design, high methodological quality, few different professions involved in the program, and study setting outside Europe.,COPD-DM programs were found to have favourable effects on both health outcomes and costs, but there is considerable heterogeneity depending on patient-, intervention-, and study-characteristics. | Objective To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients’ management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.,Design 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.,Setting 15 general practices in the eastern part of the Netherlands.,Participants Patients with COPD confirmed by spirometry and treated in general practice.,Patients with very severe COPD or treated by a respiratory physician were excluded.,Interventions A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients’ own initiative).,Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.,Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.,Results 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55).,At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant.,Secondary outcomes did not differ, except for exacerbation management.,Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).,Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice.,Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.,Trial registration Clinical trials NCT00128765. | 1 |
Outcomes for patients with chronic respiratory diseases remain poor despite the development of novel therapies.,In part, this reflects the fact that adherence to therapy is low and clinicians lack accurate methods to assess this issue.,Digital technologies hold promise to overcome these barriers to care.,For example, algorithmic analysis of large amounts of information collected on health status and treatment use, along with other disease relevant information such as environmental data, can be used to help guide personalised interventions that may have a positive health impact, such as establishing habitual and correct inhaler use.,Novel approaches to data analysis also offer the possibility of statistical algorithms that are better able to predict exacerbations, thereby creating opportunities for preventive interventions that may adapt therapy as disease activity changes.,To realise these possibilities, digital approaches to disease management should be supported by strong evidence, have a solid infrastructure, be designed collaboratively as clinically effective and cost-effective systems, and reflect the needs of patients and healthcare providers.,Regulatory standards for digital interventions and strategies to handle the large amounts of data generated are also needed.,This review highlights the opportunities provided by digital technologies for managing patients with respiratory diseases.,Digital technologies hold promise to improve adherence and personalise care in patients with respiratory diseaseshttp://ow.ly/WjTz30m71ZW | To obtain evidence whether the online pulmonary rehabilitation(PR) programme ‘my-PR’ is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD.,A two-arm parallel single-blind, randomised controlled trial.,The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility.,90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26).,Participants unable to use an internet-enabled device at home were excluded.,Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme.,A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR’.,The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of −40.5 m at −4.5 m with an upper 95% CI of +52.2 m.,This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (−13.7 to 43.8).,The CAT score difference in the ITT was −1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of −2.9.,The PP analysis was consistent with the ITT.,PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation.,A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and symptom scores and was safe and well tolerated. | 1 |
Since forced expiratory volume in 1 second (FEV1) shows a weak correlation with patients’ symptoms in COPD, some volume parameters may better reflect the change in dyspnea symptoms after treatment.,In this article, we investigated the role of inspiratory capacity (IC) on dyspnea evaluation among COPD patients with or without emphysematous lesions.,In this prospective study, 124 patients with stable COPD were recruited.,During the baseline visit, patients performed pulmonary function tests and dyspnea evaluation using the modified Medical Research Council (mMRC) scale.,Partial patients underwent quantitative computerized tomography scans under physicians’ recommendations, and emphysematous changes were assessed using the emphysema index (EI; low attenuation area [LAA]% −950).,These subjects were then divided into the emphysema-predominant group (LAA% −950≥9.9%) and the non-emphysema-predominant group (LAA% −950<9.9%).,After treatment for ~1 month, subjects returned for reevaluation of both pulmonary function parameters and dyspnea severity.,Correlation analysis between the change in IC (ΔIC) and dyspnea (ΔmMRC) was performed.,Correlation analysis revealed that ΔIC was negatively correlated with ΔmMRC (correlation coefficient [cc], −0.490, P<0.001) in the total study population, which was stronger than that between ΔFEV1 and ΔmMRC (cc, −0.305, P=0.001).,Patients with absolute ΔmMRC >1 were more likely to exhibit a marked increase in IC (≥300 mL) than those with absolute ΔmMRC ≤1 (74.36% versus 35.29%; odds ratio [OR], 5.317; P<0.001).,In the emphysema-predominant group, only ΔIC strongly correlated with ΔmMRC (cc, −0.459, P=0.005), while ΔFEV1 did not (P>0.05).,IC could serve as an effective complement to FEV1 in COPD patients undergoing dyspnea evaluation after treatment.,For COPD patients with predominant emphysematous lesions, an increase in IC is particularly more suitable for explaining dyspnea relief than FEV1. | The 1-min sit-to-stand (1-min STS) test and handgrip strength test have been proposed as simple tests of functional exercise performance in chronic obstructive pulmonary disease (COPD) patients.,We assessed the long-term (5-year) predictive performance of the 1-min sit-to-stand and handgrip strength tests for mortality, health-related quality of life (HRQoL) and exacerbations in COPD patients.,In 409 primary care patients, we found the 1-min STS test to be strongly associated with long-term morality (hazard ratio per 3 more repetitions: 0.81, 95% CI 0.65 to 0.86) and moderately associated with long-term HRQoL.,Neither test was associated with exacerbations.,Our results suggest that the 1-min STS test may be useful for assessing the health status and long-term prognosis of COPD patients.,This study was registered at http://www.clinicaltrials.gov/ (NCT00706602, 25 June 2008). | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | 1 |
COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression.,Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices.,Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.,The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines.,Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded.,Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.,Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype.,The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P<0.001), higher modified Medical Research Council grade (2.0±1.0 versus 1.7±0.9, P<0.001), and more acute exacerbations within the past year (0.9±1.3 versus 0.4±0.9, P<0.001) than the nonwheezing group.,The postbronchodilator forced expiratory volume in 1 second was lower in wheezing patients (1.2±0.5 L versus 1.5±0.6 L, P<0.001).,Even in patients with maintenance treatment fitting the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines, the wheezing group still had worse symptom scores and more exacerbations.,Wheezing is an important phenotype in patients with COPD.,Patients with COPD having the wheezing phenotype are associated with worse symptoms, more exacerbations, and worse lung function. | Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | 1 |
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398. | The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids.,However, this treatment has not been shown to reduce mortality and can potentially have serious side effects.,Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone.,By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.,This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark.,The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L.,The primary endpoint is length of hospital stay within 14 days after recruitment.,The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.,This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.,Clinicaltrials.gov, NCT02857842, 02-august-2016.,Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016. | 1 |
The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result.,On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics.,In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years).,Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12).,Forty-six asthmatics served as controls.,Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland).,Demographic data and patients’ perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed.,American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients.,Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001).,Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001).,Reversibility was equally often found in smokers as in never-smokers (33% vs 34%).,Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients.,Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI.,Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD.,In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler.,Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio.,Most patients preferred Easyhaler compared with a pMDI. | The aim of this study was to investigate patients’ inhaler competence and satisfaction with the Easyhaler® dry powder inhaler.,Two open, uncontrolled, non-randomised studies.,Real life based on patients attending 56 respiratory clinics in Hungary.,Patients with asthma or chronic obstructive pulmonary disease (COPD) (n = 1016).,In a 3-month study, adult patients (age range 18-88 years; n = 797) received twice-daily inhalations of formoterol via Easyhaler®, and in a consequential study (from one visit to another, with 3-12 months in-between) children and adolescents (age range 4-17 years; n = 219) received salbutamol via Easyhaler® as needed.,Control of six Easyhaler® handling steps and patients’ satisfaction with Easyhaler® based on questionnaires.,Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92-98 % of the adults, 87-99 % of the elderly, 81-96 % of the children and 83-99 % of the adolescents.,These figures had markedly increased at the last visit.,Repeat instructions were necessary in 26 % of the cases.,Investigators found Easyhaler® easy to teach in 87 % of the patients and difficult in only 0.5 %.,Patients found Easyhaler® easy to learn and use, and the patients’ (and parents’) satisfaction with the inhaler was very high.,Lung function values [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence.,Investigators found Easyhaler® easy to teach and patients found it easy to use, and their satisfaction with the device was high. | 1 |
Low muscle mass is associated with increased mortality in the general population but its prognostic value in at-risk smokers, those without expiratory airflow obstruction, is unknown.,We aimed to test the hypothesis that reduced muscle mass is associated with increased mortality in at-risk smokers.,Measures of both pectoralis and paravertebral erector spinae muscle cross-sectional area (PMA and PVMA, respectively) as well as emphysema on chest computed tomography (CT) scans were performed in 3705 current and former at-risk smokers (≥10 pack-years) aged 45-80 years enrolled into the COPDGene Study between 2008 and 2013.,Vital status was ascertained through death certificate.,The association between low muscle mass and mortality was assessed using Cox regression analysis.,During a median of 6.5 years of follow-up, 212 (5.7%) at-risk smokers died.,At-risk smokers in the lowest (vs. highest) sex-specific quartile of PMA but not PVMA had 84% higher risk of death in adjusted models for demographics, smoking, dyspnea, comorbidities, exercise capacity, lung function, emphysema on CT, and coronary artery calcium content (hazard ratio [HR] 1.85 95% Confidence interval [1.14-3.00] P = 0.01).,Results were consistent when the PMA index (PMA/height2) was used instead of quartiles.,The association between PMA and death was modified by smoking status (P = 0.04).,Current smokers had a significantly increased risk of death (lowest vs. highest PMA quartile, HR 2.25 [1.25-4.03] P = 0.007) while former smokers did not.,Low muscle mass as measured on chest CT scans is associated with increased mortality in current smokers without airflow obstruction.,NCT00608764,The online version of this article (10.1186/s12931-018-0771-6) contains supplementary material, which is available to authorized users. | Recent advances in multidetector computed tomography (MDCT) facilitate acquiring important clinical information for managing patients with COPD.,MDCT can detect the loss of lung tissue associated with emphysema as a low-attenuation area (LAA) and the thickness of airways as the wall area percentage (WA%).,The percentage of small pulmonary vessels <5 mm2 (% cross-sectional area [CSA] <5) has been recently recognized as a parameter for expressing pulmonary perfusion.,We aimed to analyze the longitudinal changes in structural abnormalities using these CT parameters and analyze the effect of exacerbation and smoking cessation on structural changes in COPD patients.,We performed pulmonary function tests (PFTs), an MDCT, and a COPD assessment test (CAT) in 58 patients with COPD at the time of their enrollment at the hospital and 2 years later.,We analyzed the change in clinical parameters including CT indices and examined the effect of exacerbations and smoking cessation on the structural changes.,The CAT score and forced expiratory volume in 1 second (FEV1) did not significantly change during the follow-up period.,The parameters of emphysematous changes significantly increased.,On the other hand, the WA% at the distal airways significantly decreased or tended to decrease, and the %CSA <5 slightly but significantly increased over the same period, especially in ex-smokers.,The parameters of emphysematous change were greater in patients with exacerbations and continued to progress even after smoking cessation.,In contrast, the WA% and %CSA <5 did not change in proportion to emphysema progression.,The WA% at the distal bronchi and the %CSA <5 did not change in parallel with parameters of LAA over the same period.,We propose that airway disease and vascular remodeling may be reversible to some extent by smoking cessation and appropriate treatment.,Optimal management may have a greater effect on pulmonary vascularity and airway disease than parenchymal deconstruction in the early stage of COPD. | 1 |
The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar-capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.,COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation.,At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function.,A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity.,Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD.,Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.,Airway remodelling in COPD refers to alterations of the lung ECM that affect airway wall thickness, resistance and elasticity.,Unravelling such molecular modifications will help us to identify novel biomarkers for disease progression and therapy.https://bit.ly/2LObAga | Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are the leading cause of hospital admission and death among chronic bronchitis (CB) patients.,This study estimated annual COPD exacerbation rates, related costs, and their predictors among patients treated for CB.,This was a retrospective study using claims data from the HealthCore Integrated Research Database (HIRDSM).,The study sample included CB patients aged ≥ 40 years with at least one inpatient hospitalization or emergency department visit or at least two office visits with CB diagnosis from January 1, 2004 to May 31, 2011, at least two pharmacy fills for COPD medications during the follow-up year, and ≥2 years of continuous enrollment.,COPD exacerbations were categorized as severe or moderate.,Annual rates, costs, and predictors of exacerbations during follow-up were assessed.,A total of 17,382 individuals treated for CB met the selection criteria (50.6% female; mean ± standard deviation age 66.7 ± 11.4 years).,During the follow-up year, the mean ± standard deviation number of COPD maintenance medication fills was 7.6 ± 6.3; 42.6% had at least one exacerbation and 69.5% of patients with two or more exacerbations during the 1 year prior to the index date (baseline period) had any exacerbation during the follow-up year.,The mean ± standard deviation cost per any exacerbation was $269 ± $748 for moderate and $18,120 ± $31,592 for severe exacerbation.,The number of baseline exacerbations was a significant predictor of the number of exacerbations and exacerbation costs during follow-up.,Exacerbation rates remained high among CB patients despite treatment with COPD maintenance medications.,New treatment strategies, designed to reduce COPD exacerbations and associated costs, should focus on patients with high prior-year exacerbations. | Nowadays, there is increasing awareness about the frequent chronic comorbidities in patients with chronic obstructive pulmonary disease (COPD) but little information is available to quantify the burden of illness that these conditions cause in this population.,We aimed to identify and describe a population suffering from COPD highlighting the co-morbid conditions that may contribute to poor clinical outcomes.,Epidemiological cross-sectional study conducted using administrative heath services databases.,A cohort of 126,283 COPD patients was identified.,The estimated prevalence in adult population was 3.6%.,Ninety-eight percent of these patients (123,603) received at least one prescription of “non-respiratory drugs” and, considering chronic specific comorbidities (cardiovascular disease, diabetes and depression) 86,351 patients (68.4% of COPD patients) suffered from at least one of these conditions. 80,840 pts (64.4%) were treated for cardiovascular diseases, 17,091 subjects for diabetes (12.4%) and 10,292 for depression (8%).,About 16% of COPD subjects (19,168 patients) had two out of the three considered comorbid conditions and 1352 patients (1.1%) all three.,This study highlights the complex spectrum of comorbidities in COPD patients.,The prevalence of main chronic diseases increases with age, in particular among female group.,An enhanced public awareness about these conditions is necessary, just as a more comprehensive approach in their management. | 1 |
This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT).,Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database.,MITT was defined as subjects with ≥1 overlapping days’ supply of three COPD medications (ICS, LABA, and LAMA).,Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up.,In addition, analyses were stratified by number of inhalers.,In total, 14,635 MITT users were identified (mean age, 62 years).,Mean PDC for MITT at 12 months was 0.37%.,Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively.,The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT.,Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up.,Patients with COPD had low adherence to and persistence with MITT in a real-world setting.,Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT.,Reducing the number of inhalers may improve overall adherence to intended triple therapy. | While single-inhaler triple therapy (SITT) devices were not available when the Global Initiative for Chronic Obstructive Lung Disease strategy and National Institute for Health and Care Excellence guidelines were developed, two devices are now available in the UK.,This paper offers practical, patient-focused advice to optimize placement of SITT in the management of COPD.,A survey of UK health care professionals (HCPs) identified issues around, and attitudes toward, SITT, which informed a multidisciplinary expert panel’s discussions.,The survey confirmed the need to clarify the place of SITT in COPD management.,The panel suggested three criteria, any one of which identifies a high-risk patient where escalation to triple therapy from monotherapy or double combination treatment is appropriate: 1) at least two exacerbations treated with oral corticosteroids, antibiotics, or both in the previous year; 2) at least one severe exacerbation that required hospital admission in the previous year; 3) one exacerbation a year on a repeated basis for 2 consecutive years.,Appropriate non-pharmacological management is essential for all patients and should be considered before stepping up treatment.,Regular review is essential.,During each review, HCPs should consider stepping treatment up or down.,If patients exacerbate despite adhering to triple therapy, an individualized approach should be considered if the inhaled corticosteroid (ICS) confers benefit or causes side effects.,In this situation, the blood eosinophil count could aid decision making.,ICSs should be continued when the history suggests that asthma overlaps with COPD.,Training, counseling, and education should be individualized.,HCPs should consider referral: 1) when there is limited response to treatment and persistent exacerbations; 2) where there is diagnostic uncertainty or suspected comorbidity; 3) whenever they feel “out of their depth.”,Overall, the panel concurred that when used correctly, SITT has the potential to improve adherence, symptom control, and quality of life, and reduce exacerbations.,Studies using real-world evidence need to confirm these benefits. | 1 |
Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD. | For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management. | 1 |
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function.,Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes.,NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD.,The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model.,A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours.,Cell viability was assessed by using XTT test.,Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry.,Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner.,Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone.,NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone.,NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation.,Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research. | Clinical outcomes are worse in patients with COPD and chronic bronchitis.,N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits.,We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis.,The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis.,Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial.,Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications.,The primary outcome, respiratory health status, was assessed by changes in the St George’s Respiratory Questionnaire.,The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated.,We terminated the study prematurely because new external information suggested the possibility of a safety issue.,Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study.,There was no statistically significant difference between changes in the St George’s Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, −7.8 to 8.18 U; P=0.97).,There were also no significant NAC-related improvements in any of the secondary outcomes.,In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis. | 1 |
Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team. | Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.,To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.,A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted.,COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected.,Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis.,All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.,Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities.,Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001); other comorbidities examined had moderate associations.,CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001); other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis) had moderate associations.,All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54, P<0.0001).,CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67, P<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.,This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities.,Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing.,Self-management supported by mobile device applications could improve outcomes for people with COPD.,Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care.,A systematic review was conducted to identify randomized controlled trials.,Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL).,Where possible, outcome data were pooled for meta-analyses.,Of 1709 citations returned, 13 were eligible trials.,Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported.,Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant.,There was notable variation in outcome measures used across trials.,Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD).,Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function.,Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown.,The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference.,We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18).,Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest.,More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress.,Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT < −950 Hounsfield Units (HU), and regulation of actin cytoskeleton correlated with FEV1 and FEV1/FVC in female COPD patients.,Alterations observed in the corresponding male cohort were minor.,The identified molecular pathways suggest dysregulation of several phagocytosis-related pathways in BAL cells in female COPD patients, with correlation to both the level of obstruction (FEV1/FVC) and disease severity (FEV1) as well as emphysema (CT < −950 HU) in women.,No.: NCT02627872, retrospectively registered on December 9, 2015.,The online version of this article (10.1186/s12931-017-0699-2) contains supplementary material, which is available to authorized users. | Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool.,We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent.,94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry.,Ventilation and perfusion defects were analyzed blindly according to the European guidelines.,Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease.,Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry.,Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients.,Emphysema was identified in 81 patients.,Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor.,The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages (r=0.63 and −0.60, respectively, P<0.0001).,V/P SPECT identified pulmonary embolism in 30 patients (32%).,A pattern typical for heart failure was present in 26 patients (28%).,Parenchymal changes typical for pneumonia or lung tumor were present in several cases.,V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity.,Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities.,The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis. | 1 |
Inhaled corticosteroids (ICS) might lower the risk of coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD).,This study aimed to assess the association of ICS with the development of CHD in COPD patients by using data from the Korean Nationwide study.,Patients who were newly diagnosed with COPD between 2004 and 2013 and who were not diagnosed with coronary heart disease before their diagnosis of COPD were included.,Exposure of ICS was incorporated into multivariable Cox regression models using time-dependent methods.,To accurately estimate ICS-exposure accumulation, a washout period of 2 years from 2002 to 2003 was applied.,Among a total of 4,400 newly diagnosed COPD patients, 771 patients were diagnosed as CHD incident cases during a median follow-up of one year (interquartile range 0.1-2.9).,The cumulative dose of ICS was associated with a reduced risk of CHD (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.52-0.89).,When the cumulative exposure dose of ICS was divided into quartiles, the aHR for CHD incidence was 0.70 (95% CI, 0.55-0.88) in the highest quartile ICS dose use.,The effect of ICS on reducing CHD incidence was pronounced in adults over 55 years, men under 55 years, and former smokers.,Our findings demonstrate the role of ICS for the prevention of CHD in COPD patients without a history of CHD.,Further research is needed to determine whether a certain amount of ICS exposure in COPD patients is protective against CHD. | COPD (chronic obstructive pulmonary disease) is a major incurable global health burden and will become the third largest cause of death in the world by 2020.,It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, causes progressive airflow limitation.,This inflammation, where macrophages, neutrophils and T-cells are prominent, leads to oxidative stress, emphysema, small airways fibrosis and mucus hypersecretion.,The mechanisms and mediators that drive the induction and progression of chronic inflammation, emphysema and altered lung function are poorly understood.,Current treatments have limited efficacy in inhibiting chronic inflammation, do not reverse the pathology of disease and fail to modify the factors that initiate and drive the long-term progression of disease.,Therefore there is a clear need for new therapies that can prevent the induction and progression of COPD.,Animal modelling systems that accurately reflect disease pathophysiology continue to be essential to the development of new therapies.,The present review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and whether they can be used to predict the efficacy of new therapeutics for COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change. | In patients with COPD, both laboratory exercise tests and field walking tests are used to assess physical performance.,In laboratory tests, peak exercise capacity in watts (W peak) and/or peak oxygen uptake (VO2 peak) are assessed, whereas the performance on walking tests usually is expressed as distance walked.,The aim of the study was to investigate the relationship between an incremental shuttle walking test (ISWT) and two laboratory cycle tests in order to assess whether W peak could be estimated from an ISWT.,Ninety-three patients with moderate or severe COPD performed an ISWT, an incremental cycle test (ICT) to measure W peak and a semi-steady-state cycle test with breath-by-breath gas exchange analysis (CPET) to measure VO2 peak.,Routine equations for conversion between cycle tests were used to estimate W peak from measured VO2 peak (CPET).,Conversion equation for estimation of W peak from ISWT was found by univariate regression.,There was a significant correlation between W peak and distance walked on ISWT × body weight (r = 0.88, p < 0.0001).,The agreement between W peak measured by ICT and estimated from ISWT was similar to the agreement between measured W peak (ICT) and W peak estimated from measured VO2 peak by CPET.,Peak exercise capacity measured by an incremental cycle test could be estimated from an ISWT with similar accuracy as when estimated from peak oxygen uptake in patients with COPD. | 1 |
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