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The 6-Minute Walk Test (6MWT) is representative of daily-life activities and reflects the functional capacity of patients.,The change of oxygen uptake (VO2) in the initial phase of low-intensity exercise (VO2 kinetics) can be used to assess submaximal exercise performance of patients.,The objective of the following study was to analyse VO2 kinetics in patients with different pulmonary and cardiovascular diseases.,In addition, we investigated the extent to which VO2 kinetics at the onset of the 6MWT were associated with exercise capacity, morbidity and mortality.,VO2 kinetics of 204 patients and 16 healthy controls were obtained using mobile telemetric cardiopulmonary monitoring during a 6MWT.,A new mean response time (MRT) index (wMRT) was developed to quantify VO2 kinetics by correcting MRT for work rate.,The differences in wMRT between disease categories as well as the association between wMRT and patients’ exercise capacity and outcome - time to hospitalization/death- were tested.,The assessment of a robust wMRT was feasible in 86% (244/284) patients. wMRT was increased in patients compared to healthy controls (p <0.001). wMRT was largest in patients with pulmonary arterial hypertension (PAH).,There were significant associations between wMRT and exercise capacity in all patients.,High wMRT was found to be associated with a high rate of death and re-hospitalization in patients with CHF (p = 0.024).,In patients with pulmonary diseases and pulmonary hypertension wMRT was not associated with outcome (p = 0.952).,Submaximal exercise performance of patients is reduced.,O2 kinetics at the onset of exercise are associated with exercise capacity in all patients. wMRT was found to be an important prognostic factor in patients with congestive heart failure (CHF), but not with pulmonary diseases. | Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings.,Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests.,The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV.,To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease.,The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality.,Both tests were also significantly associated with health-related quality of life but not with exacerbations.,The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62).,The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.,The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settingshttp://ow.ly/mxrPx | 1 |
There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation.,This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.,Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition.,Sputum differential cell counts (DCC) and blood DCC were obtained at baseline and 6 months.,Patients were categorised into five groups based on bacterial load defined by genome copies/ml of ≥ 1 × 104, no colonisation and colonisation by Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), or > 1 potentially pathogenic microorganism (PPM).,We observed an increase in sputum neutrophil (%), blood neutrophil (%) and neutrophil-lymphocyte ratio (NLR) in patients colonised with H. influenzae (82.6, 67.1, and 3.29 respectively) compared to those without PPM colonisation at baseline (69.5, 63.51 and 2.56 respectively) (p < 0.05 for all analyses), with similar findings at 6 months.,The bacterial load of H. influenzae and Haemophilus determined by qPCR and 16s rRNA gene sequencing respectively, and sputum neutrophil % were positively correlated between baseline and 6 months visits (p < 0.0001, 0.0150 and 0.0002 with r = 0.53, 0.33 and 0.44 respectively).,These results demonstrate a subgroup of COPD patients with persistent H. influenzae colonisation that is associated with increased airway and systemic neutrophilic airway inflammation, and less eosinophilic airway inflammation. | 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 |
Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Whether inhaled medications improve long‐term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question.,The purpose of this study is to assess the impact of adherence to inhaled drug use on 5‐year survival in COPD.,A population‐based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs).,Individuals (45+ years) discharged after COPD exacerbation in 2006-2009 were enrolled.,Inhaled drug daily use during 5‐year follow‐up was determined through Proportion of Days Covered on the basis of Defined Daily Doses.,Five levels of time‐dependent exposure were identified: (i) long‐acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB.,Cox regression models adjusted for baseline (socio‐demographic, comorbidities, drug use) and time‐dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed.,A total of 12 124 individuals were studied, 46% women, mean age 73,8 years.,Average follow‐up time 2,4 year.,A total of 3415 subjects died (mortality rate = 11.9 per 100 person years).,In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43-1.87).,Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79-0.99).,These findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate-severe COPD patients.,© 2016 The Authors.,Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. | Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms.,For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy.,Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol.,They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life.,In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated.,Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD.,A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance.,It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.,A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria.,Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these.,Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators.,Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.,The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy.,Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients. | 1 |
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. | The objective of this study was to measure health-related quality of life (HRQL) in outpatients with chronic obstructive pulmonary disease (COPD) and to assess differences in HRQL according to age, gender, and severity of COPD.,A total of 9405 patients (79% men, mean age 68 years) participated in a cross-sectional study.,HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12).,Severity of COPD was graded into three levels according to forced expiratory volume in one second value.,COPD severity was mild in 33.8% of cases, moderate in 49.3% and severe in 16.8%.,The mean physical component summary (PCS-12) and mental component summary (MCS-12) scores were 36.8 ± 10.4 and 47.2 ± 11.2, respectively.,General health and physical functioning domains were those with the lowest scores.,The mean MCS-12 scores were significantly higher in men (47.9 ± 10.9) than in women (44.1 ± 11.8) (P < 0.001).,Patients older than 60 years rated HRQL worse than patients aged 40-59 years.,There were statistically significant differences according to severity of disease in the mean scores of all domains of the PCS-12 and MCS-12 scales.,The present findings show the influence of female gender, older age and moderate-to-severe of airflow limitation on HRQL in outpatients with COPD attended in daily practice. | 1 |
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. | Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD).,To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only.,We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually.,Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations.,One-year follow-up information was available for all variables except CCQ data.,At baseline, 828 stable COPD patients were evaluated.,On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs.,27.2% in group A, 17.6% vs.,28.3% in group B, 15.8% vs.,12.9% in group C, and 28.4% vs.,31.6% in group D.,Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability.,The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722).,In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment.,A change in category after one year was associated with longitudinal changes in the CAT and BODE index. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease.,The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease.,The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10.,Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China.,The prevalence rate of COPD was higher among men (7.76%) than women (4.07%).,The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%).,The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%.,The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%.,Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD.,COPD ranked among the top three leading causes of death in China.,The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income.,The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions.,The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression.,The COPD burden in China was high in terms of economic burden and QoL.,In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. | Background: Chronic obstructive pulmonary disease (COPD) is a disease of increasing significance in terms of economic and social burden due to its increasing prevalence and high costs.,Direct costs of COPD are mostly associated with hospitalization expenditures.,In this study, our objective was to investigate the costs of hospitalization and factors affecting these costs in patients hospitalized due to acute exacerbation of COPD (AECOPD).,Methods: A total of 284 patients hospitalized AECOPD were included in the study.,Data were examined retrospectively using the electronic hospital charts.,Results: Mean duration of hospitalization was 11.38 ± 6.94 days among study patients.,Rates of admission to the intensive care unit, initiation of non-invasive mechanical ventilation (NIMV) and invasive mechanical ventilation (MIV) were 37.3% (n=106), 44.4% (n=126) and 18.3% (n=52) respectively.,The rate of mortality was 14.8% (n=42).,Mean cost of a single patient hospitalized for an AECOPD was calculated as $1765 ± 2139.,Mean cost of admission was $889 ± 533 in standard ward, and $2508 ± 2857 in intensive care unit (ICU).,The duration of hospitalization, a FEV1% predicted value below 30%, having smoked 40 package-years or more, the number of co-morbidities, NIMV, IMV, ICU, exitus and the number of hospitalizations in the past year were among the factors that increased costs significantly.,Hospital acquired pneumonia, chronic renal failure and anemia also increased the costs of COPD significantly.,Conclusion: The costs of treatment increase with the severity of COPD or with progression to a higher stage.,Efforts and expenditures aimed at preventing COPD exacerbations might decrease the costs in COPD. | 1 |
To assess and compare the prevalence of comorbidities and risk factors for cardiovascular disease (CVD) in COPD patients according to disease severity.,The study included 25 patients with mild-to-moderate COPD (68% male; mean age, 65 ± 8 years; mean FEV1, 73 ± 15% of predicted) and 25 with severe-to-very severe COPD (males, 56%; mean age, 69 ± 9 years; mean FEV1, 40 ± 18% of predicted).,Comorbidities were recorded on the basis of data obtained from medical charts and clinical evaluations.,Comorbidities were registered on the basis of data obtained from medical charts and clinical evaluations.,The Charlson comorbidity index was calculated, and the Hospital Anxiety and Depression Scale (HADS) score was determined.,Of the 50 patients evaluated, 38 (76%) had been diagnosed with at least one comorbidity, 21 (42%) having been diagnosed with at least one CVD.,Twenty-four patients (48%) had more than one CVD.,Eighteen (36%) of the patients were current smokers, 10 (20%) had depression, 7 (14%) had dyslipidemia, and 7 (14%) had diabetes mellitus.,Current smoking, depression, and dyslipidemia were more prevalent among the patients with mild-to-moderate COPD than among those with severe-to-very severe COPD (p < 0.001, p = 0.008, and p = 0.02, respectively).,The prevalence of high blood pressure, diabetes mellitus, alcoholism, ischemic heart disease, and chronic heart failure was comparable between the two groups.,The Charlson comorbidity index and HADS scores did not differ between the groups.,Comorbidities are highly prevalent in COPD, regardless of its severity.,Certain risk factors for CVD, themselves classified as diseases (including smoking, dyslipidemia, and depression), appear to be more prevalent in patients with mild-to-moderate COPD. | 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. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality. | 1 |
Chronic obstructive pulmonary disease (COPD) has a profound impact on people living with the disease and has a high global economic and social burden.,Often, people with COPD are undiagnosed, while those diagnosed are undertreated and undereducated on different aspects of COPD care.,Although there are many published evidence-based treatment guidelines from different expert groups and societies, they are frequently not adhered to, which results in significant gaps in care.,In particular, ‘flare-ups’ (known as exacerbations of COPD), which accelerate disease progression, are often under-reported, despite guidelines recommending an escalation of maintenance treatment to prevent subsequent flare-ups.,Management of COPD should be proactive to prevent worsening of symptoms and to reduce the risk of future flare-ups and premature death, rather than a secondary reaction to a worsening health status.,Key to this is patient access to accurate diagnosis, effective treatment and specialist care, which can vary widely due to socioeconomic differences, geographical locations and poor guideline implementation.,In addition, the stigma associated with COPD can act as a barrier, which can result in people being reluctant to access treatment or clinicians being nihilistic.,As global patient advocates, we have co-developed this patient charter to set a standard of care that people living with COPD should expect, raising awareness and understanding of the causes and consequences of COPD as well as the potential to improve patient care.,Patients with COPD should be empowered to live the highest quality of life possible with the least number of flare-ups.,We set out six principles in line with current COPD guideline recommendations, that should be implemented by governments, healthcare providers, policymakers, lung health industry partners and patients/caregivers to drive meaningful change in COPD care. | The prevalence of disabilities is rising steadily, reflecting an aging population and an increasing burden of chronic conditions affecting quality of life.,There are scant national data on the prevalence of disability among individuals with chronic obstructive pulmonary disease (COPD).,The main objective was to estimate the prevalence of common disabilities among US-based individuals diagnosed with COPD.,Data from the BRFSS, a national telephone survey examining health-related behaviors in 2016-2017 were analyzed.,The study population consisted of individuals with self-reported COPD (N = 38352 in 2016 and N = 35423 in 2017).,The prevalence of disabilities in hearing, vision, cognition, mobility, and independent living were obtained and adjusted with sampling weights.,Healthcare access measures were described by type of disability.,Mobility disability had the highest prevalence of 45.9 (44.8-47.0) % in 2016 and 48.4 (47.3-49.5) % in 2017 among respondents with COPD.,The prevalence of disabilities was highest among those 45-64 years old, except for hearing and cognition.,Hearing disabilities were most prevalent among males with COPD while cognitive and mobility disabilities were most prevalent among females with COPD.,While differences in the prevalence of disabilities were observed, access to health care was similar by disability type and age group among respondents.,Contrary to expectation, the highest prevalence of disabilities was found not to be among those 65 years old and above.,Further research is needed to explain this age-specific shift in the burden of disability, as long-term care planning and prevention support systems should be informed by the demographical patterns of disabilities among individuals with COPD. | 1 |
Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level.,This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation.,This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation.,Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD.,Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes.,Fourteen studies including 167 COPD patients met the inclusion criteria.,Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation.,These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine.,These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment.,The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD. | The clinical benefit of continued supervised maintenance exercise programs following pulmonary rehabilitation in COPD remains unclear.,This systematic review aimed to synthesize the available evidence on the efficacy of supervised maintenance exercise programs compared to usual care following pulmonary rehabilitation completion on health care use and mortality.,Electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science, and PEDro) and trial registers (ClinicalTrials.gov and Current Controlled Trials) were searched for randomized trials comparing supervised maintenance exercise programs with usual care following pulmonary rehabilitation completion.,Primary outcomes were respiratory-cause hospital admissions, exacerbations requiring treatment with antibiotics and/or systemic corticosteroids, and mortality.,Eight trials (790 COPD patients) met the inclusion criteria, six providing data for meta-analysis.,Continued supervised maintenance exercise compared to usual care following pulmonary rehabilitation completion significantly reduced the risk of experiencing at least one respiratory-cause hospital admission (risk ratio 0.62, 95% confidence interval [CI] 0.47-0.81, P<0.001).,Meta-analyses also suggested that supervised maintenance exercise leads to a clinically important reduction in the rate of respiratory-cause hospital admissions (rate ratio 0.72, 95% CI 0.50-1.05, P=0.09), overall risk of an exacerbation (risk ratio 0.79, 95% CI 0.52-1.19, P=0.25), and mortality (risk ratio 0.57, 95% CI 0.17-1.92, P=0.37).,In the first systematic review of the area, current evidence demonstrates that continued supervised maintenance exercise compared to usual care following pulmonary rehabilitation reduces health care use in COPD.,The variance in the quality of the evidence included in this review highlights the need for this evidence to be followed up with further high-quality randomized trials. | 1 |
Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | 1 |
Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD).,We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD.,This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation.,Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models.,The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69-84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM.,All components contributed to the CID event rate.,Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events.,The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count.,Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels.,CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development. | Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg has been shown to improve lung function and health status, and reduce exacerbations, versus budesonide/formoterol in patients with chronic obstructive pulmonary disease (COPD).,We evaluated the non-inferiority of single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers.,Eligible patients with COPD (aged ≥40 years; ≥1 moderate/severe exacerbation in the 12 months before screening) were randomized (1:1; stratified by the number of long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week FF/UMEC/VI 100/62.5/25 μg and placebo or FF/VI 100/25 μg + UMEC 62.5 μg; all treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the morning.,Primary endpoint: change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week 24.,The non-inferiority margin for the lower 95% confidence limit was set at − 50 mL.,A total of 1055 patients (844 [80%] of whom were enrolled on combination maintenance therapy) were randomized to receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528).,Mean change from baseline in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95% CI -13, 50) confirmed FF/UMEC/VI’s was considered non-inferior to FF/VI + UMEC.,At Week 24, the proportion of responders based on St George’s Respiratory Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the proportion of responders based on the Transitional Dyspnea Index focal score was similar (56% both groups).,A similar proportion of patients experienced a moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%) groups; the hazard ratio for time to first moderate/severe exacerbation with FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12).,The incidence of adverse events was comparable in both groups (48%); the incidence of serious adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC).,Single-inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI + UMEC) on trough FEV1 change from baseline at 24 weeks.,Results were similar on all other measures of efficacy, health-related quality of life, and safety.,GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31 March 2016). | 1 |
To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | COPD exacerbations accelerate disease progression.,To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration.,403 COPD patients, GOLD stage II-IV, aged 44-76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years.,Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG).,Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR).,For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity.,After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14-1.84)], age per 10 year increase [1.23 (1.03-1.47)], >1 AECOPD last year before baseline [1.65 (1.24-2.21)], GOLD III [1.36 (1.07-1.74)], GOLD IV [2.90 (1.98-4.25)], chronic cough [1.64 (1.30-2.06)] and use of inhaled steroids [1.57 (1.21-2.05)].,For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39-0.92)], years since inclusion [1.19 (1.03-1.37)], AECOPD severity; moderate [OR 1.58 (1.14-2.18)] and severe [2.34 (1.58-3.49)], season; winter [1.51 (1.08-2.12)], spring [1.45 (1.02-2.05)] and sTNF-R1 per SD increase [1.16 (1.00-1.35)].,Several COPD characteristics were independent predictors of both AECOPD frequency and duration. | 1 |
Background: Blood eosinophils may predict response to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) where ICS is recommended in patients at high risk of exacerbations.,The proportion of patients who may benefit the most from ICS-based therapy was quantified in a real-world population.,Materials and methods: European data from the Adelphi Real World Respiratory Disease Specific Programme™ 2017 survey were collected from consecutive COPD patients by participating physicians.,Overall, 1,528 patients were assessable for Global Initiative for COPD (GOLD) 2017 status and were included in the analysis.,Results: More GOLD D patients had elevated eosinophil counts compared with GOLD B.,The proportions of GOLD D patients with a history of ≥2 exacerbations and eosinophil counts of ≥150, ≥300, and ≥400 cells/µL were 81.2%, 39.4%, and 24.6%, respectively.,In total, 10.6% of the patients had ≥300 eosinophils/µL and a history of ≥2 exacerbations.,ICS-based therapy was received by 41.5% of GOLD B and 68.0% of GOLD D patients.,Conclusion: There was no apparent relation between ICS use and eosinophil blood count.,There are differences in the distributions of patients with frequent exacerbations and/or high blood eosinophil counts and the use of ICS in COPD.,These data may provide information for the implementation of future treatment recommendations. | It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD).,The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients.,Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study.,The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS).,The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models.,Among a total of 854 patients, the BDR-positive cases varied according to the criteria used.,There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria.,Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93).,This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants.,Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients.,Increase use of ICS/LABA may have affected this relationship.,The online version of this article (doi:10.1186/s12931-017-0587-9) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction.,Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis.,However, whether MgIG can treat other diseases and its action mechanism is still obscure.,In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms.,Rat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction.,Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group.,Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model.,After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45.,Normal control group were treated with normal saline.,Finally, All rats were euthanatized.,Pulmonary function was measured.,Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting.,It showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction.,Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats.,Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1.,It indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.,The online version contains supplementary material available at 10.1186/s12890-021-01745-7. | Clinical trials of a combination therapy of an inhaled corticosteroid, fluticasone propionate (FP), with a long-acting β2-agonist, salmeterol (Sal), have demonstrated a greater improvement in lung function and in quality of life measures after the combination compared with either component of alone.,In a subanalysis of the data of the TRISTAN study, Sal/FP reduced exacerbation rates in COPD patients with a baseline FEV1<50% of predicted.,A combination therapy of budesonide and formoterol improved quality of life and FEV1, and reduced exacerbations better than either component alone.,In studies of FP or of Sal/FP in COPD, there was a reduction in all-cause mortality by 25% relative to placebo.,Sal/FP has anti-inflammatory effects in COPD airways.,FP inhibits markers of systemic inflammation, and it is not known whether Sal/FP has an advantage over FP alone.,While long-acting β2-agonists such as Sal can be recommended for treatment of moderate COPD, addition of inhaled steroid therapy such as FP should be considered in more severe disease. | 1 |
Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).,Methods: The multidisciplinary panel created six research questions using a modified Delphi approach.,A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.,Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).,Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice. | Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia.,However, evidence for clinical efficacy and optimal management of therapy is limited.,Target Audience: Patients with COPD, clinicians who care for them, and policy makers.,Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions.,The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations.,Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.,Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).,Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure. | 1 |
Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
Tiotropium is reimbursed since March 2004 in Belgium for the treatment of Chronic Obstructive Pulmonary Disease (COPD).,Questions however remain on this product's value for money.,The purpose of this study is to calculate tiotropium's cost-effectiveness under real-world conditions.,Strengths of both observational and RCT data were combined in a model.,A large longitudinal (2002-2006) observational dataset of regular tiotropium users (56 321 patients) was analysed to retrieve the baseline risk for exacerbations and exacerbation-related hospitalisations the year before the first delivery of tiotropium.,The relative treatment effect from the UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial was then applied to this baseline risk to reflect the effect of tiotropium treatment and calculate the intervention's incremental cost-effectiveness ratio (ICER).,After 1000 Latin Hypercube simulations, the incremental benefit expressed as quality-adjusted life years (QALY) gained is on average 0.00048 (95% confidence interval (CI) 0.00009 - 0.00092).,In combination with a substantial mean incremental cost of €373 per patient (95% CI 279 - 475), this results in an unfavourable average ICER of €1 244 023 (95% CI 328 571 - 4 712 704) per QALY gained.,Results were most sensitive to the treatment effect on hospitalisations.,Based on our large observational database, up to 89% of the patients were not hospitalised for COPD in the year before the first tiotropium delivery.,The main cause for tiotropium's unfavourable cost-effectiveness ratio is a combination of a relative high price for tiotropium, a low number of hospitalisations without tiotropium treatment (on average 0.14/year) and a non-significant treatment effect (on average 0.94) with respect to avoiding exacerbation-related hospitalisations.,From an economic point of view, a revision of reimbursement modalities (e.g. with a lower price) would be justified and would entail a more efficient use of resources. | Our objective was to assess the 5-year cost effectiveness of bronchodilator therapy with tiotropium, salmeterol or ipratropium for chronic obstructive pulmonary disease (COPD) from the perspective of the Spanish National Health System (NHS).,A probabilistic Markov model was designed wherein patients moved between moderate, severe or very severe COPD and had the risk of exacerbation and death.,Probabilities were derived from clinical trials.,Spanish healthcare utilisation, costs and utilities were estimated for each COPD and exacerbation state.,Outcomes were exacerbations, exacerbation-free months, quality-adjusted life years (QALYs), and cost(-effectiveness).,The mean (SE) 5-year number of exacerbations was 3.50 (0.14) for tiotropium, 4.16 (0.40) for salmeterol and 4.71 (0.54) for ipratropium.,The mean (SE) number of QALYs was 3.15 (0.08), 3.02 (0.15) and 3.00 (0.20), respectively.,Mean (SE) 5-year costs were €6,424 (€305) for tiotropium, €5,869 (€505) for salmeterol, and €5,181 (€682) for ipratropium (2005 values).,Ipratropium and tiotropium formed the cost-effectiveness frontier, with tiotropium being preferred when willingness to pay (WTP) exceeded €639 per exacerbation-free month and €8,157 per QALY.,In Spain, tiotropium demonstrated the highest expected net benefit for ratios of the willingness to pay per QALY, well within accepted limits. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven. | 1 |
COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes.,Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies.,As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes.,The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites.,Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions.,However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies.,Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis.,This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms.,It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors.,Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases.,However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships. | The possible relationship between chronic inflammatory diseases and their co-morbidities has become an increasing focus of research.,Both chronic periodontitis and chronic obstructive pulmonary disease are neutrophilic, inflammatory conditions characterized by the loss of local connective tissue.,Evidence suggests an association and perhaps a causal link between the two diseases.,However, the nature of any relationship between them is unclear, but if pathophysiologically established may have wide-reaching implications for targeted treatments to improve outcomes and prognosis.,There have been a number of epidemiological studies undertaken demonstrating an independent association between chronic periodontitis and chronic obstructive pulmonary disease.,However, many of them have significant limitations, and drawing firm conclusions regarding causality may be premature.,Although the pathology of both these diseases is complex and involves many cell types, such as CD8 positive cells and macrophages, both conditions are predominantly characterized by neutrophilic inflammation.,Increasingly, there is evidence that the two conditions are underpinned by similar pathophysiological processes, especially centered on the functions of the neutrophil.,These include a disturbance in protease/anti-protease and redox state balance.,The association demonstrated by epidemiological studies, as well as emerging similarities in pathogenesis at the level of the neutrophil, suggest a basis for testing the effects of treatment for one condition upon the severity of the other.,Although the evidence of an independent association between chronic periodontitis and chronic obstructive pulmonary disease grows stronger, there remains a lack of definitive studies designed to establish causality and treatment effects.,There is a need for future research to be focused on answering these questions. | 1 |
There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD) seen in real-life clinical settings are represented in randomized controlled trials (RCTs) of COPD.,It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.,We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013.,Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline.,Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0), patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV) endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.,We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our search criteria.,The Global initiative for chronic Obstructive Lung Disease (GOLD) staging of patients in the RCTs differed from that in observational studies: the proportion of patients with GOLD stages I+II disease ranged from 40.0% to 51.5% in the RCTs but 24.5% to 44.1% in the observational studies; for GOLD stage III or IV disease these ranges were 7.2%-45.8% (RCTs) and 13.7-42.1% (observational studies).,The comorbidities with the highest prevalence reported in the RCTs and observational studies were: hypertension (39.4%-40.0% vs 40.1%-60.6%), other ischemic heart disease (12.3%-14.2% vs 12.5%-41.0%), diabetes (10.3%-10.9% vs 4.0%-38.9%), depression (8.5%-9.5% vs 17.0%-20.6%), and cardiac arrhythmia (7.8%-11.4% vs 11.3%-15.8%).,The clinical profile of COPD patients treated in the tiotropium trial program appears to be largely in the range of clinical characteristics, including cardiovascular comorbidities, reported for “real-life patients.”,The tiotropium RCTs tended to include patients with more severe disease than the observational studies. | This observational study with tiotropium Respimat® was performed in a real-life setting to investigate its effectiveness with regard to physical functioning and tolerability.,Patients with chronic obstructive pulmonary disease (COPD; n = 1,230; mean age, 65.5 years) received tiotropium 5 μg once daily via Respimat® Soft Inhaler for 6 weeks in an open-label observational study.,At baseline and week 6, patients completed the Physical Function subdomain [PF-10] of the Short Form (SF) 36 questionnaire.,Improvement in standardized PF-10 score of ≥10 points was achieved by 61.5% of patients.,Mean (SD) standardized PF-10 scores improved by 13.4 (15.9) points, from 49.0 (24.5) to 62.3 points (23.5; P < 0.001).,Results in smokers (n = 435) were not significantly different to those in nonsmokers.,The general condition of patients improved during treatment.,Adverse events were reported by 4.0% of patients and were chiefly respiratory symptoms and dry mouth.,In COPD patients receiving tiotropium Respimat® in daily practice, physical function improved rapidly within 6 weeks of treatment, irrespective of smoking status. | 1 |
Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD.,The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD.,This article analyses the evidence of efficacy and safety of the TIO/OLO combination.,A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.,A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918).,TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively).,TIO/OLO improved transitional dyspnea index (TDI) and St.,George’s Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO).,Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.,Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status.,No differences in adverse events were observed compared with other active treatments.,PROSPERO register of systematic reviews (CRD42016040162).,The online version of this article (10.1186/s12931-017-0683-x) contains supplementary material, which is available to authorized users. | The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence.,We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population.,We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013.,The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014.,During 2013, the medication collected was 7.4%-10.7% higher than indicated by labeling.,This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage.,We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule.,The results were similar in 2014.,The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device.,We did not find that patients who used twice-daily medication had a lower adherence. | 1 |
A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo.,This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study.,Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ≥10 units) received aclidinium bromide 400 μg twice daily (BID), tiotropium 18 μg once daily (QD), or placebo, for 6 weeks.,Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs) were assessed.,In all, 277 symptomatic patients were included in this post hoc analysis.,Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1) from baseline to week 6 at all time points over 24 hours versus placebo.,In addition, improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 (aclidinium 157 mL, tiotropium 67 mL; P<0.001) and week 6 (aclidinium 153 mL, tiotropium 90 mL; P<0.05).,Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (aclidinium 136 mL, tiotropium 68 mL; P<0.05) and week 6 (aclidinium 137 mL, tiotropium 71 mL; P<0.05).,Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus tiotropium (except E-RS Chest Symptoms) and placebo over 6 weeks.,Tolerability showed similar incidence of AEs in each arm.,In this post hoc analysis of symptomatic patients with moderate to severe COPD, aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity. | Morning symptoms associated with COPD have a negative impact on patients’ quality of life.,Long-acting bronchodilators with rapid onset may relieve patients’ symptoms.,In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD.,Patients were randomized (1:1) to receive either once-daily GLY (50 μg) or TIO (18 μg) and corresponding placebos in a cross-over design for 28 days.,The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours (AUC0-4h) forced expiratory volume in 1 second (FEV1) after the first dose.,The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation.,One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7 years) and 108 patients completed the study.,On Day 1, GLY resulted in significantly higher FEV1 AUC0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004-0.056, P=0.025).,Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO.,Post hoc analysis of the FEV1 AUC0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P=0.026), and 1 hour (Δ=0.044 L, P=0.014).,Safety results were comparable between both treatments.,The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO. | 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. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction and progressive lung inflammation.,As the primary ingredient of a traditional Chinese medical herb, Baicalin has been previously shown to possess anti-inflammatory abilities.,Thus, the current study aimed to elucidate the mechanism by which baicalin alleviates COPD.,Baicalin was adopted to treat cigarette smoke in extract-exposed MLE-12 cells after which cell viability and apoptosis were determined.,The production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8 were determined by enzyme-linked immunoassay.,A COPD mouse model was constructed via exposure to cigarette smoke and lipopolysaccharide, baicalin treatment.,Lung function and inflammatory cell infiltration were determined and the production of Muc5AC, TNF-α, IL-6, IL-8 in the bronchoalveolar lavage fluid (BALF) was assayed by ELISA.,The effect of HSP72 and JNK on COPD following treatment with baicalin was assessed both in vivo and in vitro by conducting loss- and gain- function experiments.,Baicalin improved lung function evidenced by reduction in inflammatory cell infiltration and Muc5AC, TNF-α, IL-6 and IL-8 levels observed in BALF in mice.,Baicalin was further observed to elevate cell viability while inhibited apoptosis and TNF-α, IL-6 and IL-8 levels in MLE-12 cells.,Baicalin treatment increased HSP72 expression, while its depletion reversed the effect of baicalin on COPD.,HSP72 inhibited the activation of JNK, while JNK activation was found to inhibit the effect of baicalin on COPD.,Baicalin upregulated the expression of HSP72, resulting in the inhibition of JNK signaling activation, which ultimately alleviates COPD.,The online version contains supplementary material available at 10.1186/s10020-021-00309-z. | Bronchodilators are the mainstay of pharmacological treatment in chronic obstructive pulmonary disease (COPD), and long-acting muscarinic antagonist (LAMA) monotherapy is recommended as initial treatment for Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, and D.,Tiotropium bromide was the first LAMA available for COPD in clinical practice and, because of its long duration of action, is administered once daily.,Tiotropium was initially available as an inhalation powder delivered via a dry-powder inhaler (DPI).,Later, tiotropium also became available as an inhalation spray delivered via a soft mist inhaler (SMI).,The SMI was designed to overcome or minimize some of the issues associated with other inhaler types (eg, the need for strong inspiratory airflow with DPIs).,Results of short- and long-term randomized, controlled clinical trials of tiotropium in patients with COPD indicated tiotropium was safe and significantly improved lung function, health-related quality of life, and exercise endurance, and reduced dyspnea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators.,These positive efficacy findings triggered the evaluation of tiotropium in fixed-dose combination with olodaterol (a long-acting β2-agonist).,In this review, we provide an overview of studies of tiotropium for the treatment of COPD, with a focus on pivotal studies.,Tiotropium is safe and efficacious as a long-term, once-daily LAMA for the maintenance treatment of COPD and for reducing COPD exacerbations.,The SMI generates a low-velocity, long-duration aerosol spray with a high fine-particle fraction, which results in marked lung drug deposition.,In addition, high inspiratory flow rates are not required. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations.,We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.,Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013.,Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days.,Exacerbations occurring within this period were considered as one event.,Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC).,To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported.,The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.,The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden.,Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.,Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations. | COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | 1 |
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 | 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 |
Comorbidities are common in COPD, but quantifying their burden is difficult.,Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life.,We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.,Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure.,We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St.,George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.,Associations between comorbidities and all outcomes were comparable across the three scores.,All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons).,Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624-0·7676), MMRC (0·7590-0·7644), 6MWD (0·7531-0·7560) and exacerbation risk (0·6831-0·6919).,Because of similar performance, the comorbidity count was used for external validation.,In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341).,Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD.,A comorbidity count performs well to quantify comorbidity in a diverse population with COPD. | Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease that affects a large number of patients and has significant impact.,One hallmark of the disease is the presence of bacteria in the lower airways.,Objective: The aim of this study was to analyze the detailed structure of microbial communities found in the lungs of healthy individuals and patients with COPD.,Nine COPD patients as compared and 9 healthy individuals underwent flexible bronchoscopy and BAL was performed.,Bacterial nucleic acids were subjected to terminal restriction fragment (TRF) length polymorphism and clone library analysis.,Overall, we identified 326 T-RFLP band, 159 in patients and 167 in healthy controls.,The results of the TRF analysis correlated partly with the data obtained from clone sequencing.,Although the results of the sequencing showed high diversity, the genera Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus constituted the major part of the core microbiome found in both groups.,A TRF band possibly representing Pseudomonas sp. monoinfection was associated with a reduction of the microbial diversity.,Non-cultural methods reveal the complexity of the pulmonary microbiome in healthy individuals and in patients with COPD.,Alterations of the microbiome in pulmonary diseases are correlated with disease. | 1 |
Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned.,This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients.,Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity.,Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed.,A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included.,Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31-0.84), which is equal to a magnitude of 1026 steps/day in daily steps.,It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16-0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance.,Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19-1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01-0.62) for patients receiving pulmonary rehabilitation.,Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50).,Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management. | More than one third of individuals with chronic obstructive pulmonary disease (COPD) experience comorbid symptoms of depression and anxiety.,This review aims to provide an overview of the burden of depression and anxiety in those with COPD and to outline the contemporary advances and challenges in the management of depression and anxiety in COPD.,Symptoms of depression and anxiety in COPD lead to worse health outcomes, including impaired health-related quality of life and increased mortality risk.,Depression and anxiety also increase health care utilization rates and costs.,Although the quality of the data varies considerably, the cumulative evidence shows that complex interventions consisting of pulmonary rehabilitation interventions with or without psychological components improve symptoms of depression and anxiety in COPD.,Cognitive behavioral therapy is also an effective intervention for managing depression in COPD, but treatment effects are small.,Cognitive behavioral therapy could potentially lead to greater benefits in depression and anxiety in people with COPD if embedded in multidisciplinary collaborative care frameworks, but this hypothesis has not yet been empirically assessed.,Mindfulness-based treatments are an alternative option for the management of depression and anxiety in people with long-term conditions, but their efficacy is unproven in COPD.,Beyond pulmonary rehabilitation, the evidence about optimal approaches for managing depression and anxiety in COPD remains unclear and largely speculative.,Future research to evaluate the effectiveness of novel and integrated care approaches for the management of depression and anxiety in COPD is warranted. | 1 |
Little is known about factors that determine health status decline in clinical trials of COPD.,To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.,St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.,Data from 4951 patients in 28 countries were available.,SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains.,SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001).,There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women.,Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1.,The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.,In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors.,Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.,ClinicalTrials.gov: NCT00268216 | The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures.,A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D.,The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS.,Age, gender, smoking status and socio-economic group were regarded as confounders.,The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023).,The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032).,No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity.,Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007).,The SGRQ Total score was significant between age groups (p = 0.0047).,No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed.,The results show that HRQL in COPD deteriorates with disease severity and with age.,These data show a relationship between HRQL and disease severity obtained by lung function. | 1 |
To evaluate the nonclinical outcomes of a proactive palliative care program funded and operated by a health system for Medicare Advantage plan beneficiaries.,Observational, retrospective study using propensity‐based matching.,A health system in southern California.,Individuals who received the intervention between 2007 and 2014 (n = 368) were matched with 1,075 comparison individuals within each of four disease groups: cancer, chronic obstructive pulmonary disease, heart failure, and dementia.,All were known to be dead at the time of the retrospective study, were Medicare Advantage beneficiaries, and had 2 years of usage data before death.,Median age at death for each disease group was older than 80.,Home‐ and clinic‐based palliative care (PC) services provided by a multidisciplinary team.,Outcomes included hospital costs, other healthcare costs, readmission rates, hospital admissions and bed days, intensive care unit use in final 30 days of life, and death within 30 days of an admission.,Intervention participants in all four disease groups had less hospital use and lower hospital costs nonintervention participants, which drove lower overall healthcare costs.,In the final 6 months of life, healthcare costs for the intervention groups stayed largely the same from month to month, whereas costs for comparison participants increased dramatically.,In the context of an alternative payment model in which the provider was “at risk” of bearing the costs of care, a proactive PC program helped to avoid the escalation in hospital use and costs commonly seen in the final months of life. | Extending palliative care to those with advanced non-malignant disease is advocated, but the implications in specific conditions are poorly understood.,We piloted a novel nurse-led intervention, HELPing older people with very severe chronic obstructive pulmonary disease (HELP-COPD), undertaken 4 weeks after discharge from hospital, which sought to identify and address the holistic care needs of people with severe COPD.,This 6-month mixed-method feasibility pilot trial randomised (ratio 3:1) patients to HELP-COPD or usual care.,We assessed the feasibility of using validated questionnaires as outcome measures and analysed the needs/actions recorded in the HELP-COPD records.,Semi-structured interviews with a purposive sample of patients, carers and professionals explored the perceptions of HELP-COPD.,Verbatim transcriptions and field notes were analysed using Normalisation Process Theory as a framework.,We randomised 32 patients (24 to HELP-COPD); 19 completed the study (death=3, ill-health=4, declined=6).,The HELP-COPD record noted a mean of 1.6 actions/assessment, mostly provision of information or self-help actions: only five referrals were made.,Most patients were positive about HELP-COPD, discussing their concerns and coping strategies in all domains, but the questionnaires were burdensome for some patients.,Adaptation to their slowly progressive disability and a strong preference to rely on family support was reflected in limited acceptance of formal services.,Professionals perceived HELP-COPD as addressing an important aspect of care, although timing overlapped with discharge planning.,The HELP-COPD intervention was well received by patients and the concept resonated with professionals, although delivery post discharge overlapped with existing services.,Integration of brief holistic care assessments in the routine primary care management of COPD may be more appropriate. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with a high global prevalence.,The main scientific societies dedicated to the management of this disease have published clinical practice guidelines for quality practice.,However, at present, there are important weaknesses in COPD diagnosis criteria that often lead to underdiagnosis or misdiagnosis.,We sought to develop a new support system for COPD diagnosis.,The system was designed to overcome the weaknesses detected in current guidelines with the goals of enabling early diagnosis, and improving the diagnostic accuracy and quality of care provided.,We first analyzed the main clinical guidelines for COPD to detect weaknesses that exist in the current diagnostic process, and then proposed a redesign based on a business process management (BPM) strategy for its optimization.,The BPM system acts as a backbone throughout the process of COPD diagnosis in this proposed approach.,The newly developed support system was integrated into a health information system for validation of its use in a hospital environment.,The system was qualitatively evaluated by experts (n=12) and patients (n=36).,Among the 12 experts, 10 (83%) positively evaluated our system with respect to increasing the speed for making the diagnosis, helping in interpreting results, and encouraging opportunistic diagnosis.,With an overall rating of 4.29 on a 5-point scale, 27/36 (75%) of patients considered that the system was very useful in providing a warning about possible cases of COPD.,The overall assessment of the system was 4.53 on a 5-point Likert scale with agreement to extend its use to all primary care centers.,The proposed system provides a functional method to overcome the weaknesses detected in the current diagnostic process for COPD, which can help foster early diagnosis, while improving the diagnostic accuracy and quality of care provided. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear.,We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.,Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007).,COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal.,Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry.,Model performance was assessed using standard criteria.,4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70.,The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76).,Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78).,The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).,Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD.,Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD. | The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003 | 1 |
To evaluate the effectiveness of long-term treatment of statins for chronic obstructive pulmonary disease (COPD), and to answer which one is better.,General meta-analysis was performed to produce polled estimates of the effect of mortality, inflammatory factors, and lung function index in COPD patients by the search of PubMed, Web of Science, Embase, and China National Knowledge Infrastructure for eligible studies.,A network meta-analysis was performed to synthetically compare the effectiveness of using different statins in COPD patients.,General meta-analysis showed that using statins reduced the risk of all-cause mortality, heart disease-related mortality and COPD acute exacerbation (AECOPD) in COPD patients, the RR (95% CI) were 0.72 (0.63,0.84), 0.72 (0.53,0.98) and 0.84 (0.79,0.89), respectively.,And using statins reduced C-reactive protein (CRP) and pulmonary hypertension (PH) in COPD patients, the SMD (95% CI) were − 0.62 (− 0.52,-0.72) and − 0.71 (− 0.85,-0.57), respectively.,Network meta-analysis showed that Fluvastatin (97.7%), Atorvastatin (68.0%) and Rosuvastatin (49.3%) had higher cumulative probability than other statins in reducing CRP in COPD patients.,Fluvastatin (76.0%) and Atorvastatin (75.4%) had higher cumulative probability than other satins in reducing PH in COPD patients.,Using statins can reduce the risk of mortality, the level of CRP and PH in COPD patients.,In addition, Fluvastatin and Atorvastatin are more effective in reducing CRP and PH in COPD patients.,The online version of this article (10.1186/s12931-019-0984-3) contains supplementary material, which is available to authorized users. | Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | 1 |
Few studies have evaluated the contribution of both viruses and bacteria in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,This study estimated the burden of both types of pathogens among adults seeking care for an AECOPD during two consecutive winter seasons.,Patients 50 years or older who consulted within 10 days of AECOPD onset were eligible.,Clinical data were collected on a standardized questionnaire, and nasopharyngeal aspirates (NPA), paired sera, and non-induced sputum were collected.,Polymerase chain reaction (PRC) assays were used to identify viral, atypical and bacterial pathogens in NPA specimen.,Overall, 108 patients with AECOPD were included, 88% of patients were admitted and 2 patients (2%) received intensive care.,A third of patients (31%) had evidence of a viral infection, 9% with influenza A, 7% RSV and 7% with PIV-3.,One patient was positive for Mycoplasma pneumoniae.,Bacterial pathogens were identified in 49% of patients with available sputum, most frequently Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae.,Among virus-infected patients, 14 (58%) also had bacteria in their sputum, but co-infected patients did not present with different symptoms than patients with single infections.,These results suggest that influenza and RSV are frequent contributors of AECOPD, and that coinfection with bacteria does not appear to be more severe among virus-infected patients.,Clinicians should be aware that AECOPD may be frequently triggered by viruses, and may consider antivirals and proper infection control measures in appropriate epidemiological setting. | The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | 1 |
Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD).,Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD.,CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs.,Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition.,The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition.,Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition.,Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition.,Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors.,Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways.,Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer. | COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking.,The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer.,We have investigated expression of these transcription factors and their “cellular localization” in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls.,An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01).,Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05).,In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4).,The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction. | 1 |
The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology.,This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD.,Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls.,The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden.,COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group.,Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m2, with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis.,The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year.,Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype.,No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers. | The relationship between serum biomarkers and clinical expressions of COPD is limited.,We planned to further describe this association using markers of inflammation and injury and repair.,We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years.,Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured.,We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].,Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs.,4).,Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).,In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival. | 1 |
COPD exacerbations accelerate disease progression.,To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration.,403 COPD patients, GOLD stage II-IV, aged 44-76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years.,Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG).,Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR).,For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity.,After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14-1.84)], age per 10 year increase [1.23 (1.03-1.47)], >1 AECOPD last year before baseline [1.65 (1.24-2.21)], GOLD III [1.36 (1.07-1.74)], GOLD IV [2.90 (1.98-4.25)], chronic cough [1.64 (1.30-2.06)] and use of inhaled steroids [1.57 (1.21-2.05)].,For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39-0.92)], years since inclusion [1.19 (1.03-1.37)], AECOPD severity; moderate [OR 1.58 (1.14-2.18)] and severe [2.34 (1.58-3.49)], season; winter [1.51 (1.08-2.12)], spring [1.45 (1.02-2.05)] and sTNF-R1 per SD increase [1.16 (1.00-1.35)].,Several COPD characteristics were independent predictors of both AECOPD frequency and duration. | The impact of COPD on patient’s quality of life is well established, but gender differences have received little attention.,To describe factors associated with the health-related quality of life by gender: A cross-sectional observational study (NCT01007734) was conducted in COPD patients followed by pulmonologists.,The first patient included had to be a woman.,Data concerning the patient, COPD and their management were collected by the physician.,The patient had to fill in several questionnaires: Saint-George Hospital respiratory Questionnaire (SGRQ-C), and motivation to quit smoking.,Four hundred and thirty patients were included: mean age 63.9 ± 11.3 years; 57.4% were women.,Women were significantly younger than men (61.9 vs.,66.6) and their tobacco use was lower (37.1 vs.,40.4 PY).,Cardiovascular comorbidities were more frequent in men while osteoporosis, anxiety and depression were frequent in women.,The frequency of cough, sputum and the severity of dyspnea did not differ significantly between genders.,Lung function impairment was less severe in women than in men (mean FEV1 52% predicted normal vs.,47.,8%).,Anxiety score was higher (score 9.8 vs.,7.1) and quality of life (SGRQ-C) more impaired in women (scores 50.6 vs.,45.4; p < 0.02) than in men.,Moreover, in multivariate analysis, chronic sputum was associated with higher SGRQ-C scores in women but not in men.,This study underlines that despite less airflow limitation, quality of life is more impacted by chronic sputum in women than in men. | 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. | Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392. | 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. | Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia.,We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn.,Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies.,Data extraction was completed independently by two reviewers.,The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration.,We included four trials; the quality of three was adequate.,In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant.,Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice.,There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes.,Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication.,In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly.,Intention to treat analyses should be used and interpreted appropriately. | 1 |
The investigation of complex disease heterogeneity has been challenging.,Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.,We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD).,We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants.,Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.,Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease severity, and genetic mechanisms. | An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity.,Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions.,We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns.,We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression differences.,The dominant characteristic in these combinations was the severity of airflow limitation.,Other frequently identified measures included emphysema, fibrinogen levels, phlegm, BMI and age.,A pathway analysis of the differentially expressed genes in the identified subtypes suggests that VIStA is capable of capturing specific molecular signatures within in each group.,The introduced methodology allowed us to identify combinations of clinical characteristics that correspond to clear gene expression differences.,The resulting subtypes for COPD contribute to a better understanding of its heterogeneity. | 1 |
Combinations of long-acting bronchodilators are recommended to reduce the rate of COPD exacerbations.,Evidence from the DYNAGITO trial showed that the fixed-dose combination of tiotropium + olodaterol reduced the annual rate of total exacerbations (P<0.05) compared with tiotropium monotherapy.,This study aimed to estimate the cost-effectiveness of the fixed-dose combination of tiotropium + olodaterol vs tiotropium monotherapy in COPD patients in the French setting.,A recently developed COPD patient-level simulation model was used to simulate the lifetime effects and costs for 15,000 patients receiving either tiotropium + olodaterol or tiotropium monotherapy by applying the reduction in annual exacerbation rate as observed in the DYNAGITO trial.,The model was adapted to the French setting by including French unit costs for treatment medication, COPD maintenance treatment, COPD exacerbations (moderate or severe), and pneumonia.,The main outcomes were the annual (severe) exacerbation rate, the number of quality-adjusted life-years (QALYs), and total lifetime costs.,The number of QALYs for treatment with tiotropium + olodaterol was 0.042 higher compared with tiotropium monotherapy.,Using a societal perspective, tiotropium + olodaterol resulted in a cost increase of +€123 and an incremental cost-effectiveness ratio (ICER) of €2,900 per QALY compared with tiotropium monotherapy.,From a French National Sickness Fund perspective, total lifetime costs were reduced by €272 with tiotropium + olodaterol, resulting in tiotropium + olodaterol being the dominant treatment option, that is, more effects with less costs.,Sensitivity analyses showed that reducing the cost of exacerbations by 34% increased the ICER to €15,400, which could still be considered cost-effective in the French setting.,Treatment with tiotropium + olodaterol resulted in a gain in QALYs and savings in costs compared with tiotropium monotherapy using a National Sickness Fund perspective in France.,From the societal perspective, tiotropium + olodaterol was found to be cost-effective with a low cost per QALY. | Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are burdened by the potential risk of inducing cardiovascular serious adverse events (SAEs) in COPD patients.,Since the risk of combining a LABA with a LAMA could be greater, we have carried out a quantitative synthesis to investigate the cardiovascular safety profile of LABA/LAMA fixed-dose combinations (FDCs).,A pair-wise and network meta-analysis was performed by using the data of the repository database ClinicalTrials.gov concerning the impact of approved LABA/LAMA FDCs versus monocomponents and/or placebo on cardiovascular SAEs in COPD.,Overall, LABA/LAMA FDCs did not significantly (P>0.05) modulate the risk of cardiovascular SAEs versus monocomponents.,However, the network meta-analysis indicated that aclidinium/formoterol 400/12 µg and tiotropium/olodaterol 5/5 µg were the safest FDCs, followed by umeclidinium/vilanterol 62.5/25 µg which was as safe as placebo, whereas glycopyrronium/formoterol 14.9/9.6, glycopyrronium/indacaterol 15.6/27.5 µg, and glycopyrronium/indacaterol 50/110 µg were the least safe FDCs.,No impact on mortality was detected for each specific FDC.,This meta-analysis indicates that LABA/LAMA FDC therapy is characterized by an excellent cardiovascular safety profile in COPD patients.,However, the findings of this quantitative synthesis have been obtained from populations that participated in randomized clinical trials, and were devoid of major cardiovascular diseases.,Thus, post-marketing surveillance and observational studies may help to better define the real impact of specific FDCs with regard to the cardiovascular risk. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) or heart failure (HF) are frequently cared for in hospital and in primary care settings.,We studied labeling agreement for COPD and HF for patients seen in both settings in Toronto, Canada.,This was a retrospective observational study using linked hospital-primary care electronic data from 70 family physicians.,Patients were 20 years of age or more and had at least one visit in both settings between 1 January 2012 and 31 December 2014.,We recorded labeling concordance and associations with clinical factors.,We used capture-recapture models to estimate the size of the populations.,COPD concordance was 34%; the odds ratios (ORs) of concordance increased with aging (OR 1.84 for age 75+ vs.,<65, 95% CI 0.92-3.69) and more inpatient admissions (OR 2.89 for 3+ visits vs. 0 visits, 95% CI 1.59-5.26).,HF concordance was 33%; the ORs of concordance decreased with aging (OR 0.39 for 75+ vs.,<65, 95% CI 0.18-0.86) and increased with more admissions (OR = 2.39; 95% CI 1.33-4.30 for 3+ visits vs. 0 visits).,Based on capture-recapture models, 21-24% additional patients with COPD and 18-20% additional patients with HF did not have a label in either setting.,The primary care prevalence was estimated as 748 COPD patients and 834 HF patients per 100,000 enrolled adult patients.,Agreement levels for COPD and HF were low and labeling was incomplete.,Further research is needed to improve labeling for these conditions.,Improving diagnostic labeling across healthcare providers would help develop a more robust database to improve care and inform research.,Patient diagnoses for serious conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), should be documented across care providers, regardless of whether a patient is seen in hospital or local surgery.,Consistent labeling of patient charts across providers improves patient services and informs research into clinical practice.,Michelle Greiver at North York General Hospital in Toronto, Canada, and co-workers uncovered significant disagreement between a Toronto hospital and its associated primary care providers on labeling of patients with HF or COPD, with the two settings agreeing on labels for a third of patients.,Around one fifth of patients had no diagnostic label in either setting, despite suffering from one or other condition. | In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality.,Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin.,A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included.,All patients underwent coronary angiography within 72 hours after hospitalization.,Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed.,Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention.,Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history.,Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01).,Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups.,Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin.,In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. | 1 |
Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult.,Incorporation of patient preferences is widely encouraged.,To summarize original research articles determining patient preference in moderate-to-severe disease.,Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma.,The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease.,We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences.,Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion.,Data were tabulated and analyzed descriptively.,About 478 articles identified, 448 were rejected and 30 analyzed.,There were 25 on COPD and five on asthma.,Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability.,Patients strongly preferred sponsors’ inhalers.,At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention.,While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience.,Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler.,Few studies have examined patient preference in these diseases.,More research is needed to fill in knowledge gaps. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 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. | T lymphocytes are believed to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,How T cells are recruited to the lungs and contribute to the inflammatory process is largely unknown.,COPD is a heterogeneous disease, and discriminating disease phenotypes based on distinct molecular and cellular pathways may provide new approaches for individualized diagnosis and therapies.,Bronchoalveolar lavage (BAL) and blood samples were obtained from 40 never-smokers, 40 smokers with normal lung function, and 38 COPD patients.,T-cell chemokine receptor expression was analyzed with flow cytometry, and soluble BAL cytokines and chemokines were measured using a cytokine multiplex assay.,Correlations with gender and clinical characteristics including lung imaging were investigated using multivariate modeling.,Th1/Tc1- and Th2/Tc2-associated soluble analytes and T-cell chemokine receptors were analyzed as cumulative Th1/Tc1 and Th2/Tc2 immune responses.,A higher expression of chemokine receptor CCR5 on CD8+ T cells in BAL and higher percentage of CXCR3+CD8+ T cells in blood was found in female smokers with COPD compared to those without COPD.,CCR5 expression on CD4+ and CD8+ T cells was lower in BAL from male smokers with COPD compared to those without COPD.,Among female smokers with COPD, Th1/Tc1 immune response was linked to BAL macrophage numbers and goblet cell density, and Th2/Tc2 response was associated with the measures of emphysema on high-resolution computed tomography.,The highly gender-dependent T-cell profile in COPD indicates different links between cellular events and clinical manifestations in females compared to males.,Our findings may reveal mechanisms of importance for the difference in clinical course in female COPD patients compared to males. | 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. | Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema.,The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects.,Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways.,20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.,Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.,Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites.,The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed.,Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens.,Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-α, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid.,Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-α, IL-13 and IL-12p40.,AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects.,NCT02557958. | 1 |
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD. | Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,It is well established that patients with mild to moderate disease represent the majority of patients with COPD, and patients with mild COPD already have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with healthy non-smoking individuals.,However, this subpopulation is both underdiagnosed and undertreated.,In addition, most clinical trials include cohorts of patients with worse lung function and quality of life, which are very different from the milder patients usually seen in primary care.,Clinical trials have shown that mild-moderate COPD patients present an improvement in lung function after treatment with long-acting bronchodilators (LABD).,Inhaled therapy has also shown benefits in terms of symptoms, health-related quality of life (HRQL) and exacerbation prevention in this population.,Early intervention might have also a positive effect to prevent functional impairment.,Nevertheless, there is scarce evidence from randomised clinical trials and real-life studies about the importance of pharmacological treatment in early stages of COPD to improve long-term outcomes.,New concepts such as clinically important deterioration may help to investigate the impact of interventions on the natural history of the disease. | 1 |
Remote patient monitoring should reduce mortality rates, improve care, and reduce costs.,We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers.,Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field.,We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain.,Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO2) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients.,We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise.,We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters.,The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems.,Graphical abstractᅟ,ᅟ | The electronic nose (e nose) provides distinctive breath fingerprints for selected respiratory diseases.,Both reproducibility and respiratory function correlates of breath fingerprint are poorly known.,To measure reproducibility of breath fingerprints and to assess their correlates among respiratory function indexes in elderly healthy and COPD subjects.,25 subjects (5 COPD patients for each GOLD stage and 5 healthy controls) over 65 years underwent e-nose study through a seven sensor system and respiratory function tests at times 0, 7, and 15 days.,Reproducibility of the e nose pattern was computed.,The correlation between volatile organic compound (VOC) pattern and respiratory function/clinical parameters was assessed by the Spearman's rho.,VOC patterns were highly reproducible within healthy and GOLD 4 COPD subjects, less among GOLD 1-3 patients.VOC patterns significantly correlated with expiratory flows (Spearman's rho ranging from 0.36 for MEF25% and sensor Co-Buti-TPP, to 0.81 for FEV1% and sensor Cu-Buti-TPP p<0.001)), but not with residual volume and total lung capacity.,VOC patterns strictly correlated with expiratory flows.,Thus, e nose might conveniently be used to assess COPD severity and, likely, to study phenotypic variability.,However, the suboptimal reproducibility within GOLD 1-3 patients should stimulate further research to identify more reproducible breath print patterns. | 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. | 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 |
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. | Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent and debilitating diseases in adults worldwide and is associated with a deleterious effect on the quality of life of affected patients.,Although it remains one of the leading causes of global mortality, the prognosis seems to have improved in recent years.,Even so, the number of patients with COPD and multiple comorbidities has risen, hindering their management and highlighting the need for futures changes in the model of care.,Together with standard medical treatment and therapy adherence - essential to optimizing disease control - several nonpharmacological therapies have proven useful in the management of these patients, improving their health-related quality of life (HRQoL) regardless of lung function parameters.,Among these are improved diagnosis and treatment of comorbidities, prevention of COPD exacerbations, and greater attention to physical disability related to hospitalization.,Pulmonary rehabilitation reduces symptoms, optimizes functional status, improves activity and daily function, and restores the highest level of independent physical function in these patients, thereby improving HRQoL even more than pharmacological treatment.,Greater physical activity is significantly correlated with improvement of dyspnea, HRQoL, and mobility, along with a decrease in the loss of lung function.,Nutritional support in malnourished COPD patients improves exercise capacity, while smoking cessation slows disease progression and increases HRQoL.,Other treatments such as psychological and behavioral therapies have proven useful in the treatment of depression and anxiety, both of which are frequent in these patients.,More recently, telehealthcare has been associated with improved quality of life and a reduction in exacerbations in some patients.,A more multidisciplinary approach and individualization of interventions will be essential in the near future. | Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires.,The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality.,Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology.,Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality.,In Canada, COPD is the fourth leading cause of death.,This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada.,A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada.,Each search was conducted using controlled vocabulary and key words, with “COPD” as the main search concept and limited to Canadian studies, written in English and involving human subjects.,Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs.,Of the 972 articles identified through the literature searches, 70 studies were included in this review.,These studies were determined to have an overall good quality based on the quality assessment.,COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits.,Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits.,Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits.,Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction.,Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living.,Evidence indicated that treating COPD improved patients’ overall quality of life.,The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective.,Furthermore, evidence indicated that COPD exacerbations lead to higher costs.,The clinical, humanistic and economic burden of COPD in Canada is substantial.,Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society. | The influence of gender on the expression of COPD has received limited attention.,Quality of Life (QoL) has become an important outcome in COPD patients.,The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients.,In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year.,We explored differences between genders using Mann-Whitney U-rank test.,To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores.,Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01).,SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001).,In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001).,Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores.,In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores.,In turn, the clinical and physiological variables independently associated with those scores differed in men and women.,Attention should be paid to the determinants of QoL scores in women with COPD. | 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.). | Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs.,Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases.,Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells.,These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease.,Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1.,MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1.,Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle.,MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6).,Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.-Baker, J.,R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P.,S., Donnelly, L.,E., Ito, K., Barnes, P.,J.,MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. | 1 |
Pentraxin 3 (PTX3) is an acute phase protein, involved in antibacterial resistance.,Recent studies have shown PTX3 levels to be elevated in the presence of a bacterial infection and in a murine sepsis model.,We aim to investigate if sputum PTX3 can be used as a biomarker for bacterial infection in subjects with COPD.,Sputum samples from 142 COPD patients (102 men) with a mean (range) age of 69 years (45-85) and mean (SD) post-bronchodilator percentage predicted forced expiratory volume in 1 second (FEV1) of 50% (19) were analyzed for PTX3, using a commercial assay at stable state and during an exacerbation.,Association with bacteria, from culture, quantitative real-time polymerase chain reaction (qPCR) and colony-forming units (CFU) was investigated.,The geometric mean (95% CI) PTX3 level at stable state was 50.5 ng/mL (41.4-61.7).,PTX3 levels correlated with absolute neutrophil count in sputum (r=0.37; P<0.01), but not FEV1 or health status.,There was a weak correlation between PTX3 and bacterial load (CFU: r=0.29, P<0.01; 16S qPCR: r=0.18, P=0.05).,PTX3 was a poor predictor of bacterial colonization (defined as >105 CFU/mL at stable state) with a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.59 and 95% confidence interval (CI) 0.43-0.76 (P=0.21).,During an exacerbation, there was a modest increase in PTX3 (fold difference 0.15, 95% of difference 0.02-0.29; P=0.02), and PTX3 fared better at identifying a bacteria-associated exacerbation (ROC AUC 0.65, 95% CI 0.52-0.78, P=0.03).,PTX3 is associated with bacterial infection in patients with COPD, but its utility as a biomarker for identifying a bacteria-associated exacerbation warrants further studies. | Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes.,Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.,To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.,In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.,Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease.,A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation.,These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection.,Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.,Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations.,The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways.,Sputum TNF-α is a candidate marker for predicting airway bacterial infection. | 1 |
This study aimed to assess the adherence rate of pharmacological treatment to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline published in 2011 and the prevalence of comorbidities among patients with COPD in Hong Kong (HK).,Patients were recruited from five tertiary respiratory centers and followed up for 12 months.,Data on baseline physiological, spirometric parameters, use of COPD medications and coexisting comorbidities were collected.,The relationship between guideline adherence rate and subsequent COPD exacerbations was assessed.,Altogether, 450 patients were recruited.,The mean age was 73.7±8.5 years, and 92.2% of them were males.,Approximately 95% of them were ever-smokers, and the mean post-bronchodilator (BD) forced expiratory volume in 1 second was 50.8%±21.7% predicted.,The mean COPD Assessment Test and modified Medical Research Council Dyspnea Scale were 13.2±8.1 and 2.1±1.0, respectively.,In all, five (1.1%), 164 (36.4%), eight (1.8%) and 273 (60.7%) patients belonged to COPD groups A, B, C and D, respectively.,The guideline adherence rate for pharmacological treatment ranged from 47.7% to 58.1% in the three clinic visits over 12 months, with overprescription of inhaled corticosteroids (ICS) and underutilization of long-acting BDs in group B COPD patients.,Guideline nonadherence was not associated with increased risk of exacerbation after adjustment of confounding variables.,However, this study was not powered to assess a difference in exacerbations.,In all, 80.9% of patients had at least one comorbidity.,A suboptimal adherence to GOLD guideline 2011, with overprescription of ICS, was identified.,The commonly found comorbidities also aligned with the trend observed in other observational cohorts. | As part of the Respiratory Disease Specific Program (DSP) conducted to provide observations of clinical practice from a physician and matched patient viewpoint, this study aimed to establish how patients with COPD are treated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system and to quantify the symptom burden.,Data were obtained from the Respiratory DSP, a cross-sectional survey of patients with a diagnosis of COPD consulting for routine care in France, Germany, Italy, Spain, the UK, and the USA during the third quarter of 2013.,Patients’ exacerbation risk and symptom data were used for classification into GOLD groups A−D based on GOLD 2014 criteria.,Prescribing practices were stratified by physician type and time since patient diagnosis.,A total of 903 physicians participated in the Respiratory DSP, with data from 1,641 patients included in this analysis.,Most patients were classified into GOLD groups B (n=742; 45.2%) and D (n=704; 42.9%).,Patients in groups A and D were most likely to be treated in line with GOLD recommendations (61.5% and 77.5%, respectively), compared with 40.1% for group B.,Patients with a diagnosis within the past 12 months were more likely to be treated according to recommendations.,Inhaled corticosteroids (ICSs) in combination with one or more long-acting bronchodilator were prescribed across all GOLD groups.,Patterns of treatment were, in general, similar for patients treated by a primary care physician or a pulmonologist.,COPD assessment test scores ≥10 indicating a high symptom burden were reported for >80% of patients.,This analysis confirmed a high symptom burden among patients with COPD and indicates some misalignment of prescribing with GOLD recommendations, particularly regarding the role of ICS/long-acting β2-agonist (LABA) and ICS/LABA + long-acting muscarinic antagonist combinations across the different GOLD groups. | 1 |
To evaluate the association of different indices of traffic-related air pollution (self-report of traffic intensity, distance from busy roads from geographical information system (GIS), area-based emissions of particulate matter (PM), and estimated concentrations of nitrogen dioxide (NO2) from a land-use regression model) with respiratory health in adults.,A sample of 9488 25-59-year-old Rome residents completed a self-administered questionnaire on respiratory health and various risk factors, including education, occupation, housing conditions, smoking, and traffic intensity in their area of residence.,The study used GIS to calculate the distance between their home address and the closest high-traffic road.,For each subject, PM emissions in the area of residence as well as estimated NO2 concentrations as assessed by a land-use regression model (R2 value = 0.69), were available.,Generalised estimating equations (GEE) were used to analyse the association between air pollution measures and prevalence of “ever” chronic bronchitis, asthma, and rhinitis taking into account the effects of age, gender, education, smoking habits, socioeconomic position, and the correlation of variables for members of the same family.,Three hundred and ninety seven subjects (4% of the study population) reported chronic bronchitis, 472 (5%) asthma, and 1227 (13%) rhinitis.,Fifteen per cent of subjects reported living in high traffic areas, 11% lived within 50 m of a high traffic road, and 28% in areas with estimated NO2 greater than 50 μg/m3.,Prevalence of asthma was associated only with self-reported traffic intensity whereas no association was found for the other more objective indices.,Rhinitis, on the other hand, was strongly associated with all traffic-related indicators (eg, OR = 1.13, 95% CI: 1.04 to 1.22 for 10 μg/m3 NO2), especially among non-smokers.,Indices of exposure to traffic-related air pollution are consistently associated with an increased risk of rhinitis in adults, especially among non-smokers.,The results for asthma are weak, possibly due to ascertainment problems. | Several studies have shown cross-sectional associations between long term exposure to particulate air pollution and survival in general population or convenience cohorts.,Less is known about susceptibility, or year to year changes in exposure.,We investigated whether particles were associated with survival in a cohort of persons with COPD in 34 US cities, eliminating the usual cross-sectional exposure and treating PM10 as a within city time varying exposure.,Using hospital discharge data, we constructed a cohort of persons discharged alive with chronic obstructive pulmonary disease using Medicare data between 1985 and 1999. 12-month averages of PM10 were merged to the individual annual follow up in each city.,We applied Cox's proportional hazard regression model in each city, with adjustment for individual risk factors.,We found significant associations in the survival analyses for single year and multiple lag exposures, with a hazard ratio for mortality for an increase of 10 μg/m3 PM10 over the previous 4 years of 1.22 (95% CI: 1.17-1.27).,Persons discharged alive for COPD have substantial mortality risks associated with exposure to particles.,The risk is evident for exposure in the previous year, and higher in a 4 year distributed lag model.,These risks are significantly greater than seen in time series analyses. | 1 |
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations.,We assessed risk factors for bacterial colonisation in COPD.,Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis.,Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture.,Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load.,A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated.,Bacterial colonisation was demonstrated in 58 (48.7%) patients.,Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour.,Thirty-six patients (62% of those colonised) had a high bacterial load.,More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture.,In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001).,Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.,Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs.,Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised. | 1 |
AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines.,The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines.,An organisational database was completed by all participant hospitals recording resources and organisation.,Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified.,At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population.,Audited patients were reassessed 90 days after admission for survival and readmission rates.,A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death.,Median inpatient mortality was 5% (across-hospital range 0-35%).,Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%).,The overall mortality rate was 11.6% (0-50%).,Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment.,Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles.,The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes.,The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. | Chronic Obstructive Pulmonary Disease (COPD) accounts for around 4% of all public hospital annual admissions in Hong Kong.,By year 2020, COPD will be ranked fifth among the conditions with the highest burden to the society.,This study identifies admission and unplanned readmission of COPD patients, factors affecting unplanned readmission, and estimates its cost burden on the public healthcare system in Hong Kong.,This is a retrospective study analyzing COPD admissions to all public hospitals in Hong Kong.,All admission episodes to acute medical wards with the principal diagnosis of COPD (ICD-9:490-492, 494-496) from January 2006 to December 2007 were captured.,Unplanned readmission was defined as an admission which followed a previous admission within 30 days.,In 2006 and 2007, 65497 (8.0%) of episodes from medical wards were identified as COPD admissions, and among these, 15882 (24.2%) were unplanned readmissions.,The mean age of COPD patients was 76.81 ± 9.59 years and 77% were male.,Unplanned readmission was significantly associated with male gender, receiving public assistance and living in nursing homes while no association was found with the Charlson comorbidity index.,Patients who were readmitted unplanned had a significant longer acute length of stay (β = 0.3894, P < 0.001) after adjustment for other covariates.,Unplanned readmission of COPD patients has a huge impact on the public healthcare system.,A systematic approach in programme provision and a good discharge planning process targeting on COPD patients who are at high risk of unplanned readmission are essential. | 1 |
The process of aging involves biological changes that increases susceptibility for disease.,In the aging lung disease IPF, GWAS studies identified genes associated with risk for disease.,Recently, several of these genes were also found to be involved in risk for COPD or lung cancer.,This review describes GWAS-derived risk genes for IPF that overlap with risk genes for lung cancer or COPD.,Risk genes that overlap between aging lung diseases, include FAM13A, DSP and TERT.,Most interestingly, disease predisposing alleles for IPF are opposite to those for COPD or lung cancer.,Studies show that the alleles are associated with differential gene expression and with physiological traits in the general population.,The opposite allelic effect sizes suggest the presence of trade-offs in the aging lung.,For TERT, the trade-off involves cellular senescence versus proliferation and repair.,For FAM13A and DSP, trade-offs may involve protection from noxious gases or tissue integrity.,The overlap in risk genes in aging lung diseases provides evidence that processes associated with FAM13A, DSP and TERT are important for healthy aging.,The opposite effect size of the disease risk alleles may represent trade-offs, for which a model involving an apicobasal gene expression gradient is presented. | Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear.,We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.,Sputum was collected from 174 stable COPD subjects longitudinally over 12 months.,Microbial sampling using culture and qPCR was performed.,Spirometry and sputum measures of airway inflammation were assessed.,Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]).,Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL.,Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts.,H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive.,Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.,qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods. | 1 |
Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited.,The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass.,Eighty‐one COPD patients with low muscle mass, admitted to out‐patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega‐3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training.,The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid.,Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048).,After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001).,Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (−18%,P = 0.005).,High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction.,Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo. | Decreased physical activity is associated with higher mortality in subjects with COPD.,The aim of this study was to assess clinical characteristics and physical activity levels (PALs) in subjects with COPD.,Seventy-three subjects with COPD (67 ± 7 yrs, 44 female) with one-second forced expiratory volume percentage (FEV1%) predicted values of 43 ± 16 were included.,The ratio of total energy expenditure (TEE) and resting metabolic rate (RMR) was used to define the physical activity level (PAL) (PAL = TEE/RMR).,TEE was assessed with an activity monitor (ActiReg), and RMR was measured by indirect calorimetry.,Walking speed (measured over 30-meters), maximal quadriceps muscle strength, fat-free mass and systemic inflammation were measured as clinical characteristics.,Hierarchical linear regression was applied to investigate the explanatory values of the clinical correlates to PAL.,The mean PAL was 1.47 ± 0.19, and 92% of subjects were classified as physically very inactive or sedentary.,The walking speed was 1.02 ± 0.23 m/s, the quadriceps strength was 31.3 ± 11.2 kg, and the fat-free mass index (FFMI) was 15.7 ± 2.3 kg/m2, identifying 42% of subjects as slow walkers, 21% as muscle-weak and 49% as FFM-depleted.,The regression model explained 45.5% (p < 0.001) of the variance in PAL.,The FEV1% predicted explained the largest proportion (22.5%), with further improvements in the model from walking speed (10.1%), muscle strength (7.0%) and FFMI (3.0%).,Neither age, gender nor systemic inflammation contributed to the model.,Apart from lung function, walking speed and muscle strength are important correlates of physical activity.,Further explorations of the longitudinal effects of the factors characterizing the most inactive subjects are warranted. | 1 |
Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease.,To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations.,This was a 2-year prospective cohort study of COPD patients.,Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared.,Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002).,For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001).,Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation.,In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
COPD is a common complex disease characterized by progressive airflow limitation.,Several genome-wide association studies (GWASs) have discovered genes that are associated with COPD.,Recently, candidate genes for COPD identified by GWASs include CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), FAM13A (family with sequence similarity 13, member A), and AGER (advanced glycosylation end product-specific receptor).,Their association with COPD susceptibility has been replicated in multiple populations.,Since these candidate genes have not been considered in COPD, their pathological roles are still largely unknown.,Herein, we review some evidences that they can be effective drug targets or serve as biomarkers for diagnosis or subtyping.,However, more study is required to understand the functional roles of these candidate genes.,Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and posttranscriptional regulatory mechanisms. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with usual care.,Design 24 month, multicentre, pragmatic cluster randomised controlled trial,Setting 40 general practices in the western part of the Netherlands,Participants Patients with COPD according to GOLD (Global Initiative for COPD) criteria.,Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse, and inability to fill in Dutch questionnaires.,Practices were included if they were willing to create a multidisciplinary COPD team.,Intervention General practitioners, practice nurses, and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice, including early recognition of exacerbations and self management, smoking cessation, physiotherapeutic reactivation, optimal diagnosis, and drug adherence.,Additionally, the course served as a network platform and collaborating healthcare providers designed an individual practice plan to integrate integrated disease management into daily practice.,The control group continued usual care (based on international guidelines).,Main outcome measures The primary outcome was difference in health status at 12 months, measured by the Clinical COPD Questionnaire (CCQ); quality of life, Medical Research Council dyspnoea, exacerbation related outcomes, self management, physical activity, and level of integrated care (PACIC) were also assessed as secondary outcomes.,Results Of a total of 1086 patients from 40 clusters, 20 practices (554 patients) were randomly assigned to the intervention group and 20 clusters (532 patients) to the usual care group.,No difference was seen between groups in the CCQ at 12 months (mean difference -0.01, 95% confidence interval -0.10 to 0.08; P=0.8).,After 12 months, no differences were seen in secondary outcomes between groups, except for the PACIC domain “follow-up/coordination” (indicating improved integration of care) and proportion of physically active patients.,Exacerbation rates as well as number of days in hospital did not differ between groups.,After 24 months, no differences were seen in outcomes, except for the PACIC follow-up/coordination domain.,Conclusion In this pragmatic study, an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care, except improved level of integrated care and a self reported higher degree of daily activities.,The contradictory findings to earlier positive studies could be explained by differences between interventions (provider versus patient targeted), selective reporting of positive trials, or little room for improvement in the already well developed Dutch healthcare system.,Trial registration Netherlands Trial Register NTR2268. | Favorable effects of formal pulmonary rehabilitation in selected moderate to severe COPD patients are well established.,Few data are available on the effects and costs of integrated disease management (IDM) programs on quality of care and health status of COPD patients in primary care, representing a much larger group of COPD patients.,Therefore, the RECODE trial assesses the long-term clinical and cost-effectiveness of IDM in primary care.,RECODE is a cluster randomized trial with two years of follow-up, during which 40 clusters of primary care teams (including 1086 COPD patients) are randomized to IDM or usual care.,The intervention started with a 2-day multidisciplinary course in which healthcare providers are trained as a team in essential components of effective COPD IDM in primary care.,During the course, the team redesigns the care process and defines responsibilities of different caregivers.,They are trained in how to use feedback on process and outcome data to guide implement guideline-driven integrated healthcare.,Practice-tailored feedback reports are provided at baseline, and at 6 and 12 months.,The team learns the details of an ICT program that supports recording of process and outcome measures.,Afterwards, the team designs a time-contingent individual practice plan, agreeing on steps to be taken in order to integrate a COPD IDM program into daily practice.,After 6 and 12 months, there is a refresher course for all teams simultaneously to enable them to learn from each other’s experience.,Health status of patients at 12 months is the primary outcome, measured by the Clinical COPD Questionnaire (CCQ).,Secondary outcomes include effects on quality of care, disease-specific and generic health-related quality of life, COPD exacerbations, dyspnea, costs of healthcare utilization, and productivity loss.,This article presents the protocol and baseline results of the RECODE trial.,This study will allow to evaluate whether IDM implemented in primary care can positively influence quality of life and quality of care in mild to moderate COPD patients, thereby making the benefits of multidisciplinary rehabilitation applicable to a substantial part of the COPD population.,Netherlands Trial Register (NTR): NTR2268 | 1 |
Analytic epidemiological studies cover a large spectrum of study methodologies, ranging from noninterventional observational studies (population-based, case-control, or cohort studies) to interventional studies (clinical trials).,Herein, we review the different research methodologies or study designs and discuss their advantages and disadvantages in the context of chronic obstructive pulmonary disease (COPD) pharmacotherapy.,Although randomized controlled trials (RCTs) are considered the “gold standard” for evaluating the efficacy and safety of an intervention, observational studies conducted in a real-world scenario are useful in providing evidence on the effectiveness of the intervention in clinical practice; understanding both efficacy and effectiveness is important from the clinician’s perspective.,Pragmatic clinical trials that use real-world data while retaining randomization bridge the gap between explanatory RCTs and noninterventional observational studies.,Overall, different study designs have their associated advantages and disadvantages; together, findings from all types of studies bring about progress in clinical research as elucidated through examples from COPD research in this paper. | Chronic obstructive pulmonary disease (COPD) is common in older people, with an estimated prevalence of 10% in the US population aged ≥75 years.,Inhaled medications are the cornerstone of treatment for COPD and are typically administered by one of three types of devices, ie, pressurized metered dose inhalers, dry powder inhalers, and nebulizers.,However, age-related pulmonary changes may negatively influence the delivery of inhaled medications to the small airways.,In addition, physical and cognitive impairment, which are common in elderly patients with COPD, pose special challenges to the use of handheld inhalers in the elderly.,Health care providers must take time to train patients to use handheld inhalers and must also check that patients are using them correctly on a regular basis.,Nebulizers should be considered for patients unable to use handheld inhalers properly.,What follows is a review of issues associated with COPD and its treatment in the elderly patient. | 1 |
Background and objective: Viruses are important aetiological agents of acute exacerbation of COPD (AECOPD).,Their reported prevalence varies from region to region.,This systematic review calculated the prevalence of respiratory viral infections in AECOPD.,Methods: A systematic search was performed using Medline, and references of relevant articles and conference proceedings were hand searched.,Articles for review were selected based on the following criteria: (i) prospective or cross‐sectional study, (ii) original research, (iii) viral detection used the highly sensitive techniques of PCR and/or Reverse Transcriptase PCR (RT‐PCR), (iv) viral prevalence in AECOPD defined, and (v) full paper available in English.,We assessed the study quality and extracted data independently and in duplicate using a pre‐defined data extraction form.,Weighted mean prevalence (WMP) was calculated and a forest plot was constructed to show the dispersion.,Results: Eight studies met the inclusion criteria.,The WMP of respiratory viral infection in AECOPD was 34.1% (95% CI: 23.9-44.4). picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2-27.3), followed by influenza; 7.4% (95% CI: 2.9-12.0), respiratory syncytial virus; 5.3% (95% CI: 1.6-9.0), corona viruses; 3.1% (95% CI: 0.4-5.8), parainfluenza; 2.6% (95% CI: 0.4-4.8), adenovirus; 1.1% (95% CI: −1.1 to 3.3), and human metapneumovirus; 0.7% (95% CI: −0.3 to 1.8).,Maximum WMP was observed in studies from Europe followed by the USA, Australia and Asia.,Picorna was the most common virus detected in Western countries whereas influenza was most common in Asia.,Conclusions: This systematic review demonstrated that viruses are strongly associated with AECOPD, with the highest detection rates of viruses being in Europe.,The geographical epidemiology of viruses may have important therapeutic implications for management of AECOPD.,Viruses are an important cause of acute exacerbation of COPD (AECOPD).,This systematic review calculated the weighted mean prevalence (WMP) of respiratory viruses detected in patients with AECOPD.,The overall WMP was 34.1% (95% CI: 23.9‐44.4), and picornavirus was the most commonly detected virus with WMP 17.3% (95% CI: 7.2‐27.3). | Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization.,The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013.,Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years.,Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups.,Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions).,From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%.,Mean age at diagnosis was 66 years and 52.0% were male.,Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81-0.85) for GOLD A to 2.51 (95% CI: 2.47-2.55) for GOLD D.,General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74-4.93) for GOLD A to 7.44 (95% CI: 7.31-7.61) for GOLD D.,COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84).,Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits.,Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization. | 1 |
Chronic obstructive pulmonary disease (COPD) is widely underdiagnosed.,A number of studies have evaluated the accuracy of screening tests for COPD, but their findings have not been formally summarised.,We therefore sought to determine and compare the diagnostic accuracy of such screening tests in primary care.,Systematic review and meta-analysis of the diagnostic accuracy of screening tests for COPD confirmed by spirometry in primary care.,We searched MEDLINE, EMBASE and other bibliographic databases from 1997 to 2013 for diagnostic accuracy studies that evaluated 1 or more index tests in primary care among individuals aged ≥35 years with no prior diagnosis of COPD.,Bivariate meta-analysis of sensitivity and specificity was performed where appropriate.,Methodological quality was assessed independently by 2 reviewers using the QUADAS-2 tool.,10 studies were included. 8 assessed screening questionnaires (the COPD Diagnostic Questionnaire (CDQ) was the most evaluated, n=4), 4 assessed handheld flow meters (eg, COPD-6) and 1 assessed their combination.,Among ever smokers, the CDQ (score threshold ≥19.5; n=4) had a pooled sensitivity of 64.5% (95% CI 59.9% to 68.8%) and specificity of 65.2% (52.9% to 75.8%), and handheld flow meters (n=3) had a sensitivity of 79.9% (95% CI 74.2% to 84.7%) and specificity of 84.4% (68.9% to 93.0%).,Inadequate blinding between index tests and spirometry was the main risk of bias.,Handheld flow meters demonstrated higher test accuracy than the CDQ for COPD screening in primary care.,The choice of alternative screening tests within whole screening programmes should now be fully evaluated.,CRD42012002074. | Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | 1 |
Given the heterogeneity of chronic obstructive pulmonary disease (COPD), personalized clinical management is key to optimizing patient outcomes.,Important treatment goals include minimizing disease activity and preventing disease progression; however, quantification of these components remains a challenge.,Growing evidence suggests that decline over time in forced expiratory volume in 1 s (FEV1), traditionally the key marker of disease progression, may not be sufficient to fully determine deterioration across COPD populations.,In addition, there is a lack of evidence showing that currently available multidimensional COPD indexes improve clinical decision-making, treatment, or patient outcomes.,The composite clinically important deterioration (CID) endpoint was developed to assess disease worsening by detecting early deteriorations in lung function (measured by FEV1), health status (assessed by the St George’s Respiratory Questionnaire), and the presence of exacerbations.,Post hoc and prospective analyses of clinical trial data have confirmed that the multidimensional composite CID endpoint better predicts poorer medium-term outcomes compared with any single CID component alone, and that it can demonstrate differences in treatment efficacy in short-term trials.,Given the widely acknowledged need for an individualized holistic approach to COPD management, monitoring short-term CID has the potential to facilitate early identification of suboptimal treatment responses and patients at risk of increased disease progression.,CID monitoring may lead to better-informed clinical management decisions and potentially improved prognosis. | Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline.,Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed.,We evaluated post hoc the link between early CID and long-term adverse outcomes.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies.,Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE).,Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed.,In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+.,At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (- 117 mL; 95% confidence interval [CI]: - 134, - 100 mL; P < 0.001) and SGRQ score (+ 6.42 units; 95% CI: 5.40, 7.45; P < 0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P < 0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P < 0.001).,Similar risks post-CID were observed in ECLIPSE.,A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors.,NCT00268216; NCT00292552.,The online version of this article (10.1186/s12931-018-0928-3) contains supplementary material, which is available to authorized users. | 1 |
Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A) plays an important role in pulmonary host defense.,Based on the knowledge that chronic obstructive pulmonary disease (COPD) starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels.,The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations.,Patients with stable COPD ranging from moderate to very severe (n = 13), and healthy non-smoking subjects (n = 12) were studied.,Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA® instrument setup.,Immunoassays were used to quantify SP-A and albumin.,COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs.,3.9 weight percent, p = 0.036) and lower particle number concentration (p<0.0001) than healthy subjects.,Albumin mass contents were similar for both groups.,Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations.,SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients. | Air pollution, mainly from combustion, is one of the leading global health risk factors.,A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD).,There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles.,To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing.,Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber.,The respiratory tract deposition of the particles was measured in the size range 10-500 nm during spontaneous breathing.,The deposited dose rate increased with increasing severity of the disease.,However, the deposition probability of the ultrafine combustion particles (< 100 nm) was decreased in COPD patients.,The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function.,The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability.,The strong correlations between lung function and particle deposition, especially in the size range of 20-30 nm, suggest that altered particle deposition could be used as an indicator respiratory disease. | 1 |
Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases.,This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population.,We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS.,The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS.,Poisson regression was used to compare the frequency of respiratory adverse events.,At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs.,41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs.,36%; ICS vs. no ICS, respectively).,Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs.,0.056 respectively; p = 0.012).,When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs.,0.058, respectively; p < 0.001).,COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs.,0.84 respectively; p = 0.013).,ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown.,In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation.,The online version of this article (doi:10.1007/s00408-017-9990-8) contains supplementary material, which is available to authorized users. | Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326 | 1 |
COPD remains under-recognized and under-treated.,Much of early COPD care is given by primary care physicians but only when COPD is recognized.,This survey explores the attitudes, beliefs, and knowledge related to COPD recognition, diagnosis, and treatment from family physicians and nurse practitioners (NPs) and physician assistants (PAs) working in primary care.,We completed a survey of family physicians, and NPs/PAs attending one of three CME programs on five common chronic conditions including COPD.,Return rate was 62% (n = 284) including 178 physicians and 100 NPs/PAs.,Fewer than half of the respondents reported knowledge of or use of COPD guidelines.,The barriers to recognition and diagnosis of COPD they reported included the multiple morbidities of most COPD patients, failure of patients to report COPD symptoms, as well as lack of knowledge and inadequate training in COPD diagnosis and management.,Three quarters (74%) of respondents reported use of spirometry to diagnose COPD but only 32% said they included reversibility assessment.,COPD was incorrectly assessed as a disease primarily of men (78% of respondents) that appeared after age 60 (61%).,Few respondents reported that they believed COPD treatment was useful or very useful for improving symptoms (15%) or decreasing exacerbations (3%) or that pulmonary rehabilitation was helpful (3%), but 13% reported they thought COPD treatment could extend longevity.,Primary care physicians and NPs/PAs working in primary care continue to report lack of awareness and use of COPD guidelines, as well as correct information related to COPD epidemiology or potential benefits of available treatments including pulmonary rehabilitation.,It is unlikely that diagnosis and management of COPD will improve in primary care until these knowledge gaps and discrepancies with published efficacy of therapy issues are addressed. | Chronic obstructive pulmonary disease (COPD) is a significant health problem worldwide.,This randomised controlled trial aims at testing a new approach that involves a registered nurse working in partnership with patients, general practitioners (GPs) and other health professionals to provide care to patients according to the evidence-based clinical practice guidelines.,The aim is to determine the impact of this partnership on the quality of care and patient outcomes.,A cluster randomised control trial design was chosen for this study.,Randomisation occurred at practice level.,GPs practising in South Western Sydney, Australia and their COPD patients were recruited for the study.,The intervention was implemented by nurses specifically recruited and trained for this study.,Nurses, working in partnership with GPs, developed care plans for patients based on the Australian COPDX guidelines.,The aim was to optimise patient management, improve function, prevent deterioration and enhance patient knowledge and skills.,Control group patients received 'usual' care from their GPs.,Data collection includes patient demographic profiles and their co-morbidities.,Spirometry is being performed to assess patients' COPD status and CO analyser to validate their smoking status.,Patients' quality of life and overall health status are being measured by St George's Respiratory Questionnaire and SF-12 respectively.,Other patient measures being recorded include health service use, immunisation status, and knowledge of COPD.,Qualitative methods will be used to explore participants' satisfaction with the intervention and their opinion about the value of the partnership.,Analysis will be by intention to treat.,Intra-cluster (practice) correlation coefficients will be determined and published for all primary outcome variables to assist future research.,The effect of the intervention on outcomes measured on a continuous scale will be estimated and tested using mixed model analysis of variance in which time and treatment group will be fixed effects and GP practice and subject nested within practice will be random effects.,The effect of the intervention on the dichotomous variables (such as smoking status, patient knowledge) will be analysed using generalised estimating equations with a logistic link and a model structure that is analogous to that described above.,ACTRN012606000304538 | 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. | The aim of the study was to investigate how the expression of adhesion molecules changes as neutrophils migrate from the circulation to the lung and if these changes differ between non-smoking subjects and smokers with and without COPD.,Non-smoking healthy subjects (n=22), smokers without (n=21) and with COPD (n=18) were included.,Neutrophils from peripheral blood, sputum and bronchial biopsies were analysed for cell surface expression of adhesion molecules (CD11b, CD62L, CD162).,Serum, sputum supernatant and BAL-fluid were analysed for soluble adhesion molecules (ICAM-1, -3, E-selectin, P-selectin, VCAM-1, PECAM-1).,Expression of CD11b was increased on circulating neutrophils from smokers with COPD.,It was also increased on sputum neutrophils in both smokers groups, but not in non-smokers, as compared to circulating neutrophils.,Serum ICAM-1 was higher in the COPD group compared to the other two groups (p<0.05) and PECAM-1 was lower in smokers without COPD than in non-smoking controls and the COPD group (p<0.05).,In BAL-fluid ICAM-1 was lower in the COPD group than in the other groups (p<0.05).,Thus, our data strongly support the involvement of a systemic component in COPD and demonstrate that in smokers neutrophils are activated to a greater extent at the point of transition from the circulation into the lungs than in non-smokers. | 1 |
The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results. | The evidence that sharing mass care quality data with health service users improves care is weak.,We hypothesised that providing patients with individualised care quality data would drive improvements to the care received by those patients.,Together with patients who had chronic obstructive pulmonary disease (COPD), we co-designed a quality score card mapping indicators derived from National Institute for Clinical Excellence (NICE) quality standards against matched data taken from their general practice clinical records.,All 640 COPD patients from 10 practices had improvements in these indicators before and 3 months after the intervention compared with 595 COPD patients in 10 control practices.,Significant improvements in referral to pulmonary rehabilitation (P=0.03) and confirmation of diagnosis with spirometry (P=0.001) were seen in the intervention compared with the control practice population (P<0.001).,Increases in the provision of self-management plans were seen in both the groups.,No improvement was seen in other indicators.,Although the study is not able to prove a direct cause and effect, there is sufficient evidence presented to warrant the larger-scale evaluation of co-designed, personalised, quality score cards for COPD patients used as a tool to enhance care quality. | 1 |
This study aimed to explore the relation between lymphocyte to high-density lipoprotein ratio (LHR) and pulmonary function of chronic obstructive pulmonary disease (COPD) patients compared with neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR).,In total, 154 participants (n = 77 with COPD and n = 77 without COPD) were recruited.,LHR, NLR, PLR, lung function and other data were collected and compared.,Pearson’s correlation test and the receiver operating characteristics curves were used to compare the utility of LHR, NLR and PLR.,Besides, univariate and multivariate logistic regression analyses were conducted.,COPD patients with poorer lung function had a lower LHR level (P < 0.001).,In low LHR group, more patients underwent greater airflow limitation than the other group (P = 0.006).,LHR positively correlated with forced expiratory volume in 1 second in percent of the predicted value (FEV1%) (r = 0.333, P = 0.003).,At a cut-off value of 2.08, the sensitivity and specificity of LHR in predicting FEV1% < 50 were 93.2% and 55.6%, respectively, with an AUC of 0.770 (P = 0.001) better than NLR and PLR.,Based on logistic regression analyses, it was proved that LHR was associated with decreased risk of FEV1 <50% predicted in COPD patients (odds ratio = 0.198, 95% CI: 0.048-0.811, P = 0.024).,In contrast with NLR and PLR, LHR has higher accuracy for predicting pulmonary function in COPD; lower LHR level is independently associated with poorer pulmonary function. | Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress.,Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation.,However, no data on the possible relationship between COPD and ox-LDL are available.,This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress.,Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits.,Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62 ± 7.56 versus 12.57 ± 5.90 mU/L, P < 0.05).,Serum levels of CRP and ROS were also significantly higher in COPD patients.,Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r = −0.347, P = 0.016), while they correlated positively with CRP and ROS levels.,These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.,Future studies are needed to determine whether and how ox-LDL plays a role in COPD. | 1 |
Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended. | The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS).,Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group.,Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA).,Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed.,IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05).,IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001).,IL-10 level was significantly different between each of the 2 groups (all P<0.001).,TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001).,IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC.,Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS. | 1 |
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend triple therapy (TT) for chronic obstructive pulmonary disease (COPD) patients based on severity.,TT utilization by severity is infrequently studied in real-world settings and may deviate significantly from current clinical recommendations.,This study describes prescribing pathways to TT among patients with COPD in the United States.,This study analyzed Geisinger Health System electronic medical records from 1 January 2004 to 30 November 2016.,Two retrospective cohorts of COPD patients were included: (1) incident COPD, and (2) incident TT users.,COPD treatment patterns, including time to TT, were summarized.,Time to TT was estimated using Kaplan-Meier methods.,Predictors of the relative hazard for TT among incident COPD patients were estimated using Cox proportional hazards regressions.,Incident COPD and TT cohorts included 57,141 and 8173 patients, respectively.,TT was used by 9.6% of incident COPD patients.,In the year before TT, 34.3% of incident TT patients received treatment combinations recommended before TT according to GOLD recommendations, which mainly included: long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs) + LAMAs, and inhaled corticosteroids + LABAs.,Among incident TT patients, median time from COPD diagnosis to TT exceeded 2 years.,The hazard for TT over time was associated with lower forced expiratory volume in 1 s values, more frequent exacerbations, current/previous smoking, and comorbid lung conditions such as pulmonary vascular disease, acute respiratory failure, and lung cancer.,About 15-20% of the incident TT patients stepped down to a one- or two-drug regimen.,Median time to TT discontinuation or step-down were 2 and 9 months, respectively.,The study has revealed discrepancies in the treatment of COPD patients between GOLD guidelines and actual clinical practices in the United States.,Pathways to TT differed from recommended therapy regimes.,Further studies are needed to understand barriers to the use of guideline-recommended TTs by healthcare providers.,The reviews of this paper are available via the supplemental material section. | Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens.,International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations.,Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD.,Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use.,We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence.,Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes.,Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality.,These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA.,Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons.,Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making.,We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes. | 1 |
Asthma and chronic obstructive pulmonary disease are inflammatory lung disorders responsible for significant morbidity and mortality worldwide.,While the importance of allergic responses in asthma is well known, respiratory viral and bacterial infections and pollutants especially cigarette smoke are important factors in the pathogenesis of both diseases.,Corticosteroid treatment remains the first preference of treatment in either disease, however these therapies are not always completely effective, and are associated with side effects and steroid resistance.,Due to such limitations, development of new treatments represents a major goal for both the pharmaceutical industry and academic researchers.,There are now excellent reasons to promote NF-κB signalling intermediates and Rel family proteins as potential therapeutic targets for both asthma and chronic obstructive pulmonary disease.,This notion is supported by the fact that much of the underlying inflammation of both diseases independent of stimuli, is mediated at least in part, by NF-κB mediated signalling events in several cell types.,Also, a range of inhibitors of NF-κB signalling intermediates are now available, including DNA oligonucleotides and DNA-peptide molecules that act as NF-κB decoy sequences, small molecule inhibitors such as IKK-β inhibitors, and proteasome inhibitors affecting NF-κB signalling, that have either shown promise in animal models or have begun clinical trials in other disorders.,This review will focus on the role of NF-κB in both diseases, will discuss its suitability as a target, and will highlight recent key studies that support the potential of NF-κB as a therapeutic target in these two important inflammatory lung diseases. | COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | 1 |
Supplemental Digital Content is available in the text,This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature.,Literature was searched in several electronic databases.,After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model.,Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients’ data) were used for meta-analysis.,Average age of COPD patients was 66.66 ± 8.72 years of whom 55.4 ± 11.9% were males.,The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls.,COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
The aim of the study was to assess the relationship between computed tomography (CT) densitometry and routine clinical markers in patients with chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency (AATD).,Multiple databases were searched using a combination of pertinent terms and those articles relating quantitatively measured CT densitometry to clinical outcomes.,Studies that used visual scoring only were excluded, as were those measured in expiration only.,A thorough review of abstracts and full manuscripts was conducted by 2 reviewers; data extraction and assessment of bias was conducted by 1 reviewer and the 4 reviewers independently assessed for quality.,Pooled correlation coefficients were calculated, and heterogeneity was explored.,A total of 112 studies were identified, 82 being suitable for meta-analysis.,The most commonly used density threshold was −950 HU, and a significant association between CT density and all included clinical parameters was demonstrated.,There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters.,CT density shows a good relationship to clinically relevant parameters; however, study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinically important difference.,We recommend that international consensus is reached to standardize CT conduct and analysis in future COPD and AATD studies. | The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role.,Reduced plasma levels of soluble RAGE (sRAGE) have been reported in patients with chronic obstructive pulmonary disease (COPD).,The aim of the present study was to evaluate the association of plasma sRAGE levels with a longitudinal decline of lung function.,We have also measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD.,Baseline plasma concentrations of sRAGE and HMGB1 were measured in non-smokers (n = 32), smokers without COPD (n = 212), and smokers with COPD (n = 51), and the associations of the plasma sRAGE and HMGB1 levels with longitudinal declines of lung function during a 4-year follow-up period were analysed.,The plasma levels of sRAGE were significantly lower in smokers without COPD and in smokers with COPD, as compared to those of non-smokers.,Plasma sRAGE levels positively correlated with FVC and FEV1 and inversely correlated with BMI and pack-years.,Lower sRAGE levels were associated with greater declines of FEV1/FVC over 4 years in all participants.,Moreover, multivariate regression analysis indicated that the baseline plasma sRAGE concentration was an independent predictor of FEV1/FVC decline in all groups.,A subgroup analysis showed that decreased sRAGE levels are significantly associated with a more rapid decline of FEV1/FVC in smokers with COPD.,There was no significant correlation between plasma HMGB1 levels and longitudinal decline of lung function.,Lower plasma concentrations of sRAGE were associated with greater progression of airflow limitations over time, especially in smokers with COPD, suggesting that RAGE might have a protective role in the lung. | 1 |
Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
The stigma of non-communicable respiratory diseases (NCRDs), whether perceived or otherwise, can be an important element of a patient’s experience of his/her illness and a contributing factor to poor psychosocial, treatment and clinical outcomes.,This systematic review examines the evidence regarding the associations between stigma-related experiences and patient outcomes, comparing findings across a range of common NCRDs.,Electronic databases and manual searches were conducted to identify original quantitative research published to December 2015.,Articles focussing on adult patient samples diagnosed with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, lung cancer or mesothelioma, and included a measurement of stigma-related experience (i.e. perceived stigma, shame, blame or guilt), were eligible for inclusion.,Included articles were described for study characteristics, outcome scores, correlates between stigma-related experiences and patient outcomes and methodological rigor.,Twenty-five articles were eligible for this review, with most (n = 20) related to lung cancer.,No articles for cystic fibrosis were identified.,Twenty unique scales were used, with low to moderate stigma-related experiences reported overall.,The stigma-related experiences significantly correlated with all six patient-related domains explored (psychosocial, quality of life, behavioral, physical, treatment and work), which were investigated more widely in COPD and lung cancer samples.,No studies adequately met all criteria for methodological rigor.,The inter-connectedness of stigma-related experiences to other aspects of patient experiences highlight that an integrated approach is needed to address this important issue.,Future studies should adopt more rigorous methodology, including streamlining measures, to provide robust evidence. | Studies suggest that COPD prevalence may vary between countries.,We conducted an ecological study of data from COPD prevalence articles to assess the influence of differences in country-level risk factors on COPD prevalence.,Our study covered English language articles published during 2003-2014.,Qualified articles used spirometry to assess COPD prevalence and used representative samples from national or subnational populations.,Stepwise binomial regression was used to analyze associations between study- and country-level factors and COPD prevalence.,Eighty articles provided 1,583 measures of COPD prevalence for subjects in different sex, age, and smoking categories for 112 districts in 41 countries.,Adjusted prevalence rates for COPD were significantly lower for Australia/New Zealand and the Mediterranean and significantly higher for Latin America, compared to North America, Southeast Asia, and Northern Europe.,Country-level socioeconomic development variables had an uneven and mixed association with COPD prevalence.,High elevation above sea level was shown to be a protective factor for COPD.,Study-level variables for the established risk factors of sex, age, and smoking explained 64% of variability in COPD prevalence.,Country-level risk factors raised the explanatory power to 72%.,Approximately 28% of worldwide variability in COPD prevalence remained unexplained.,Our study suggests that COPD prevalence varies across world regions, even after adjustment for established risk factors.,Major country-level risk factors contributing to the worldwide epidemic of COPD remain to be investigated. | 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. | Current primary care patterns for chronic obstructive pulmonary disease (COPD) focus on reactive care for acute exacerbations, often neglecting ongoing COPD management to the detriment of patient experience and outcomes.,Proactive diagnosis and ongoing multifactorial COPD management, comprising smoking cessation, influenza and pneumonia vaccinations, pulmonary rehabilitation, and symptomatic and maintenance pharmacotherapy according to severity, can significantly improve a patient’s health-related quality of life, reduce exacerbations and their consequences, and alleviate the functional, utilization, and financial burden of COPD.,Redesign of primary care according to principles of the chronic care model, which is implemented in the patient-centered medical home, can shift COPD management from acute rescue to proactive maintenance.,The chronic care model and patient-centered medical home combine delivery system redesign, clinical information systems, decision support, and self-management support within a practice, linked with health care organization and community resources beyond the practice.,COPD care programs implementing two or more chronic care model components effectively reduce emergency room and inpatient utilization.,This review guides primary care practices in improving COPD care workflows, highlighting the contributions of multidisciplinary collaborative team care, care coordination, and patient engagement.,Each primary care practice can devise a COPD care workflow addressing risk awareness, spirometric diagnosis, guideline-based treatment and rehabilitation, and self-management support, to improve patient outcomes in COPD. | 1 |
Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo.,Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast.,A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler.,Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only).,Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6-136.9 L/min), pressure drops (1.2-13.8 kPa), and inhaled volumes through the inhaler (0.7-4.2L).,DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed.,Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy.,Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy.,Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency. | Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD).,The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD.,Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax.,Dose consistency was assessed over inhaler life.,Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler.,The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits.,In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study.,Results: Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected).,In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min.,The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min.,Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use.,Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are often nonadherent with medications and have poor inhaler technique.,Community pharmacists can help to improve health-related quality of life and overall outcomes in patients with COPD.,We aim to measure the effectiveness of a systematic, pharmacist-driven intervention on patients with diagnosed COPD.,This pragmatic, parallel-group, cluster randomized controlled trial is designed to determine the effectiveness of a multifactorial, pharmacist-led intervention on medication adherence, inhaler technique, health-related quality of life, health care resource utilization including COPD exacerbations, and use of medications.,Participating pharmacies in Newfoundland and Labrador (NL), Canada will be randomly assigned to either the intervention or the control group.,The intervention group will deliver an enhanced form of care that emphasizes COPD management.,The control group will provide usual care and a COPD education pamphlet.,Included patients will be aged 40 years or older, have a physician-confirmed diagnosis of COPD, and be able to answer questionnaires in English.,The primary outcomes are the between-group difference in the change from baseline to 6 months in medication adherence using the Medication Possession Ratio (MPR) and the Morisky Medication Adherence Scale (MMAS-8).,The secondary outcomes are also measured from baseline to 6 months, and include the proportion of patients with a clinically significant change in adherence, the proportion of patients defined as having “good adherence,” the mean MPR between groups, quality of life as measured by the St.,George’s Respiratory Questionnaire, medication inhalation technique using a pharmacist-scored checklist, health care resource utilization and antibiotic and orally administered corticosteroid use for COPD exacerbations.,Differences between groups will be analyzed at the individual patient level while controlling for clustering effect.,A pharmacist-led COPD intervention has the potential to improve patient medication adherence, thus increasing quality of life, possibly decreasing pulmonary exacerbations and reducing utilization of acute health care resources.,Methods and results taken from this study could be used to enhance the delivery of COPD care by community pharmacists in a real-world setting.,This would serve to enhance COPD population health and quality of life.,International Standard Randomized Controlled Trial Number (ISRCTN) ISRCTN78138190, registered on 3 February 2016.,The online version of this article (doi:10.1186/s13063-016-1623-7) contains supplementary material, which is available to authorized users. | Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients.,Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers.,A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA).,The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted.,The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09).,Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models.,Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included.,These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients.,Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality.,Further research is warranted to strengthen this conclusion.,The online version of this article (doi:10.1186/s12890-015-0138-4) contains supplementary material, which is available to authorized users. | 1 |
Complete blood count parameters provide novel inflammatory markers, namely neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR).,We aimed to assess any differences in these novel inflammatory markers according to exacerbation severity in patients with COPD in both eosinophilic and neutrophilic endotypes.,This retrospective cross-sectional study was conducted at a tertiary education hospital.,Previously diagnosed COPD patients admitted to the hospital with acute COPD exacerbation (AECOPD) were enrolled into the study.,Patients were grouped according to COPD endotype, eosinophilic (peripheral blood eosinophil rate ≥2%) and neutrophilic (peripheral blood eosinophil rate <2%), and further subdivided according to place of admission (outpatient clinic, ward, or intensive care unit [ICU]) as an indicator of disease severity.,Complete blood count, biochemistry, C-reactive protein (CRP), NLR, PLR, and platelet to mean platelet volume values were recorded from an electronic hospital database system and compared among all groups.,Of the 10,592 patients included in the study, 7,864 were admitted as outpatients, 2,233 to the wards, and 495 to ICU.,Neutrophilic COPD patients (n=6,536, 62%) had increased inflammatory markers compared with eosinophilic COPD patients (n=4,056, 38%); median NLR was 5.11 vs 2.62 (P<0.001), PLR was 175.66 vs 130.00 (P<0.001), and CRP was 11.6 vs 7.7 (P<0.001).,All values increased relative to admission to the outpatient clinic, ward, or ICU: median NLR was 3.20, 6.33, and 5.94, respectively, median PLR was 140.43, 208.46, and 207.39, respectively, and median CRP was 6.4, 15.0, and 22.8, respectively.,The median NLR values of patients in outpatients/ward/ICU increased in neutrophilic and eosinophilic endotypes: 4.21/7.57/8.60 (P<0.001) and 2.50/3.43/3.42 (P=0.81), respectively.,CRP showed a similar increased pattern according to severity of AECOPD endotypes.,In COPD exacerbation, the inflammatory markers show different increases in each COPD endotypes.,These findings may be crucial for defining exacerbation endotypes, the severity of exacerbation, and treatment response during follow-up in COPD patients. | Cardiovascular disease (CVD) is remarkably frequent in patients with chronic obstructive pulmonary disease (COPD).,Albuminuria is a marker of vascular endothelial dysfunction and predictor of CVD events.,Albuminuria is prevalent in patients with COPD as it has been shown in Caucasian and Oriental populations with COPD.,The objective of this study was to determine the prevalence of Albuminuria and COPD severity correlates among black patients with chronic obstructive pulmonary disease in order to see whether a similar trend of albuminuria is also prevalent in this population.,A total of 104 COPD patients were enrolled in the study.,Lung functions were assessed by means of the Easy One™ spirometer.,Albuminuria defined by urine albumin to creatinine ratio (ACR) was tested using CYBOW 12MAC microalbumin strips in a random spot urine collection.,SPSS version 20 was used for data analysis.,In the studied population, 25/104 (24%) patients had albuminuria and 16/104 (15.4%) patients had CVD.,Abnormal urine albumin (Albuminuria and Proteinuria) was present in all patients with CVD.,In the subset of 46 COPD patients assessed for severity, 60.9% (95%CIs 46.1-73.9) had moderate COPD and 30.4% (95% CIs, 17.9-49.0) severe COPD.,Albuminuria was moderately significantly associated with COPD severity, p = 0.049; (0.049 < p < 0.05).,Participants who ever smoked cigarettes had significantly likelihood of severe and very severe COPD (OR 11.5; 95% CIs, 1.3, 98.4) however, the significance was lost when adjusted for age and gender.,Albuminuria was prevalent in patients with COPD and it had a significant association with COPD severity. | 1 |
The Halifax-based INSPIRED COPD Outreach Program™ is a facility-to-community home-based novel clinical initiative that through improved care transitions, self-management, and engagement in advance care planning has demonstrated a significant (60%-80%) reduction in health care utilization with substantial cost aversion.,By assessing the feasibility of expanding INSPIRED into the emergency department (ED) we anticipated extending reach and potential for positive impact of INSPIRED to those with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) who avoid hospital admission.,Patients were eligible for the INSPIRED-ED study if >40 years of age, diagnosed with AECOPD and discharged from the ED, willing to be referred, community dwelling with at least one of: previous use of the ED services, admission to Intermediate Care Unit/Intensive Care Unit, or admission to hospital with AECOPD in the past year.,We set feasibility objectives for referral rates, completion of action plans, advance care planning participation, and reduction in ED visit frequency.,Referral rates were 0.5/week.,Among eligible patients (n=174) 33 (19%) were referred of whom 15 (M=4, F=11) enrolled in INSPIRED-ED.,Mean (SD) age was 68 (7) years, post-bronchdilator FEV1 44.2 (15.5) % predicted, and Medical Research Council (MRC) dyspnea score 3.8 (0.41).,We met feasibility objectives for action plan and advance care planning completion.,Frequency of subsequent ED visits fell by 54%.,Mean (SD) Care Transition Measure (CTM-3) improved from 8.6 (2.0) to 11.3 (1.3), P=0.0004, and of 14 patients responding 12 (86%) found the program very helpful.,An additional 34 patients were enrolled to our regular program from those referred but ineligible for INSPIRED-ED (n=27) or unwilling to participate (n=7).,INSPIRED-ED outcomes were generally positive, however referral and enrollment rates were lower than anticipated.,Despite the potential of early self-management education, the ED may not be the ideal recruitment setting for home-based programs.,Our findings underline the importance of conducting preliminary work to ascertain best settings for implementing new self-management education initiatives. | Chronic obstructive pulmonary disease (COPD) is a leading cause of hospital admission, the fifth leading cause of death in North America, and is estimated to cost $49 billion annually in North America by 2020.,The majority of COPD care costs are attributed to hospitalizations; yet, there are limited data to understand the drivers of high costs among hospitalized patients with COPD.,In this study, we aimed to determine the patient and hospital-level factors associated with high-cost hospital care, in order to identify potential targets for the reorganization and planning of health services.,We conducted a retrospective cohort study at a Canadian academic hospital between September 2010 and 2014, including adult patients with a first-time admission for COPD exacerbation.,We calculated total costs, ranked patients by cost quintiles, and collected data on patient characteristics and health service utilization.,We used multivariable regression to determine factors associated with highest hospital costs.,Among 1,894 patients included in the study, the mean age was 73±12.6 years, median length of stay was 5 (interquartile range 3-9) days, mortality rate was 7.8% (n=147), and 9% (n=170) required intensive care.,Hospital spending totaled $19.8 million, with 63% ($12.5 million) spent on 20% of patients.,Factors associated with highest costs for COPD care included intensive care unit admission (odds ratio [OR] 32.4; 95% confidence interval [CI] 20.3, 51.7), death in hospital (OR 2.6; 95% CI 1.3, 5.2), discharge to long-term care facility (OR 5.7; 95% CI 3.5, 9.2), and use of the alternate level of care designation during hospitalization (OR 23.5; 95% CI 14.1, 39.2).,High hospital costs are driven by two distinct groups: patients who require acute medical treatment for severe illness and patients with functional limitation who require assisted living facilities upon discharge.,Improving quality of care and reducing cost in this high-needs population require a strong focus on early recognition and management of functional impairment for patients living with chronic disease. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal and chronic inflammatory response in the lung that underlies the chronic airflow obstruction of the small airways, the inexorable decline of lung function, and the severity of the disease.,The control of this inflammation remains a key strategy for treating the disease; however, there are no current anti-inflammatory treatments that are effective.,Although glucocorticoids (GCs) effectively control inflammation in many diseases such as asthma, they are less effective in COPD.,The molecular mechanisms that contribute to the development of this relative GC-insensitive inflammation in the lung of patients with COPD remain unclear.,However, recent studies have indicated novel mechanisms and possible therapeutic strategies.,One of the major mechanisms proposed is an oxidant-mediated alteration in the signaling pathways in the inflammatory cells in the lung, which may result in the impairment of repressor proteins used by the GC receptor to inhibit the transcription of proinflammatory genes.,Although these studies have described mechanisms and targets by which GC function can be restored in cells from patients with COPD, more work is needed to completely elucidate these and other pathways that may be involved in order to allow for more confident therapeutic targeting.,Given the relative GC-insensitive nature of the inflammation in COPD, a combination of therapies in addition to a restoration of GC function, including effective alternative anti-inflammatory targets, antioxidants, and proresolving therapeutic strategies, is likely to provide better targeting and improvement in the management of the disease. | 1 |
Sarcopenia and decreased bone-mineral density (BMD) are common in elderly people, and are major comorbidities of obstructive airway disease (OAD).,However, the relationship between sarcopenia and BMD in each OAD phenotype, especially asthma-COPD overlap syndrome (ACOS), is not yet clear.,We aimed to evaluate differences in BMD according to the presence of sarcopenia in each OAD phenotype.,Among the research subjects in KNHANES IV and V (2008-2011), 5,562 were ≥50 years old and underwent qualified spirometry and dual-energy X-ray absorptiometry.,A total of 947 subjects were included in the study: 89 had asthma, 748 COPD, and 110 ACOS.,In the COPD and ACOS phenotypes, T-scores were lower in the sarcopenia group than the nonsarcopenia group.,Prevalence rates of osteopenia and osteoporosis were higher in the sarcopenia group than the nonsarcopenia group.,(P<0.001 and P=0.017, respectively).,The sarcopenia group had higher risks of developing osteopenia, osteoporosis, and low BMD than the nonsarcopenia group in the ACOS phenotype (OR 6.620, 95% CI 1.129-38.828 [P=0.036], OR 9.611, 95% CI 1.133-81.544 [P=0.038], and OR 6.935, 95% CI 1.194-40.272 [P=0.031], respectively).,However, in the asthma phenotype, the sarcopenia group showed no increased risk compared with the nonsarcopenia group.,In the ACOS phenotype, individuals with sarcopenia had a higher prevalence rate and higher risks of osteopenia and osteoporosis than those without sarcopenia among all OAD phenotypes. | Patients with COPD are at an increased risk of osteoporosis.,Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD.,In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD.,In total, 200 patients with COPD were included in this study.,The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples.,BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry.,Other clinical parameters were also evaluated.,Haplotype and multivariate analyses were also performed.,Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis.,Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD.,Haplotypes GCT and GAT were related to osteoporosis.,Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model.,Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD.,Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD. | 1 |
The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease.,We investigated 91 patients with COPD and 21 healthy nonsmokers.,The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied.,An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected.,The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD.,The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease. | Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking.,Increased oxidative burden plays an important role in the pathogenesis of COPD.,There is a delicate balance between the toxicity of oxidants and the protective function of the intracellular and extracellular antioxidant defense systems, which is critically important for the maintenance of normal pulmonary functions.,Several biomarkers of oxidative stress are available and have been evaluated in COPD.,In this review, we summarize the main literature findings about circulating oxidative stress biomarkers, grouped according to their method of detection, measured in COPD subjects. | 1 |
COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of their disease, sometimes requiring hospital admission and being associated with increased mortality.,Although previous studies have reported mortality from exacerbations of COPD, there is limited information about prediction of individual in-hospital mortality.,We therefore aimed to use data from a nationwide inpatient database in Japan to generate a nomogram for predicting in-hospital mortality from patients’ characteristics on admission.,We retrospectively collected data on patients with COPD who had been admitted for exacerbations and been discharged between July 1, 2010 and March 31, 2013.,We performed multivariable logistic regression analysis to examine factors associated with in-hospital mortality and thereafter used these factors to develop a nomogram for predicting in-hospital prognosis.,The study comprised 3,064 eligible patients.,In-hospital death occurred in 209 patients (6.8%).,Higher mortality was associated with older age, being male, lower body mass index, disturbance of consciousness, severe dyspnea, history of mechanical ventilation, pneumonia, and having no asthma on admission.,We developed a nomogram based on these variables to predict in-hospital mortality.,The concordance index of the nomogram was 0.775.,Internal validation was performed by a bootstrap method with 50 resamples, and calibration plots were found to be well fitted to predict in-hospital mortality.,We developed a nomogram for predicting in-hospital mortality of exacerbations of COPD.,This nomogram could help clinicians to predict risk of in-hospital mortality in individual patients with COPD exacerbation. | Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes.,We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006-2012.,We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%).,Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation.,Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012.,Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period.,A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures.,Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17-1.24).,Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11-1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07-1.13).,In contrast, the aHR of a subsequent exacerbation was 8%-13% lower for patients with pneumonic exacerbations.,Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality.,Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations. | 1 |
Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood.,A number of candidate genes have been proposed on the basis of the pathogenesis of COPD.,These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD.,Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies.,To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations.,We used logistic regression to adjust for age, gender, centre and smoking history.,Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV.,Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94).,The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129).,This implicates haplotypes of MMP-12 as modifiers of disease severity. | The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation. | 1 |
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects.,This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches.,In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%).,Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.).,Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ).,Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ).,The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ).,Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement.,MCID estimates differed depending on the method used.,Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients.,The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD. | Enhancing quality of life for people with long-term conditions by monitoring patient-reported outcome measure scores is a key domain of health care policy.,This study investigated the responsiveness of patient-reported outcome measures for long-term conditions.,A cohort survey was conducted in 33 primary care practices and 4485 patients (1334 asthma, 567 chronic obstructive pulmonary disease, 1121 diabetes, 525 epilepsy, 520 heart failure and 418 stroke) were sent a baseline survey containing a generic (EQ-5D) and a disease-specific measure.,Baseline respondents were sent a follow-up after 1 year.,Differences in scores for each long-term condition were assessed by paired t-tests.,The relationship between scores and self-reported ‘change in health’ was assessed by analysis of variance.,The baseline achieved a 38.4% response rate and the follow-up 71.5%.,The only significant difference for the EQ-5D was found for the Visual Analogue Scale in heart failure between baseline and follow-up, and for change in health.,Significant differences between baseline and follow-up scores were found on the disease-specific measures for 1 asthma dimension and 1 stroke dimension.,No significant differences were found for other conditions.,Significant differences between self-reported change in health and the disease-specific measures were found for 4 asthma dimensions and 2 stroke dimensions.,Few significant differences were found between the baseline and follow up or between ‘change in health’ and PROMs scores.,This could be explained by the time frame of one year being too short for change to occur or by the PROMs not being responsive enough to change in a primary care sample.,The latter is unlikely as the PROMs were in part chosen for their responsiveness to change.,The baseline response rates may mean that the sample is not representative, and stable patients may have been more likely to participate.,If PROMs are to be used routinely to monitor outcomes in LTCs, further research is needed to maximize response rates, to ensure that the PROMs used are reliable, valid and sensitive enough to detect change and that the time frame for data collection is appropriate.,The online version of this article (doi:10.1186/s12955-014-0123-2) contains supplementary material, which is available to authorized users. | 1 |
Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management.,Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease.,Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics.,To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management.,To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction.,An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people).,Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena.,(1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering.,The results indicate the high potential of a systems approach to address COPD heterogeneity.,Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD. | Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation.,Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy.,Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate.,In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators.,Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles.,Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization.,These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. | 1 |
Pain is a clinical complication to chronic obstructive pulmonary disease (COPD) that interferes negatively with physical activity level (PAL), quality of life (QOL) and pulmonary interventions.,Yet, research in pain characteristics including prevalence, localization, and intensity in people with COPD are sparsely researched.,To investigate self-reported pain prevalence, localization and intensity of pain in people with and without COPD, and to investigate the association between pain intensity and PAL among participants with COPD.,Data were derived from the Danish Health and Morbidity Survey in 2017.,The study population was restricted to individuals aged ≥35 years.,Data included pain intensity assessed on the Numeric Rating Scale (NRS) and localization, PAL, QoL, sleep disturbance, comorbidities, sociodemographic and behavioral factors.,In all, 528 participants with COPD and 8184 participants without COPD (51% females, mean ±SD age 67.1±11.4 years) were analyzed.,Pain prevalence within the past 14 days was significantly higher in participants with COPD vs nonCOPD (72.7% vs 57.7%, p<0.001) and mainly located in the limbs, thorax, and lower back.,COPD was associated with the prevalence of chronic pain (≥6 months) (OR: 2.78, 95%CI: 2.32; 3.34, p<0.001).,Participants with COPD reported a higher pain intensity compared to those with nonCOPD with a mean difference of 1.04 points (95%CI: 0.75; 1.32, p<0.001) on the NRS.,In the adjusted multiple logistic regression analysis, pain intensity was negatively associated with odds of being physical active (OR: 0.72, 95%CI: 0.61; 0.85, p<0.001).,Pain is more prevalent in people with self-reported COPD.,After adjustment for age and gender, COPD was associated with an elevated pain intensity.,Sleep disturbance and multimorbidity had the most pronounced impacts on pain intensity in the multiple linear regression model.,In participants with COPD, increased pain intensity was negatively associated with being physically active. | Objective: To find out how regularly the contents of patient education regarded as essential for COPD patients’ self-management are provided by healthcare professionals in specialised healthcare (SHC) and primary healthcare (PHC) in Finland.,Design: A cross-sectional study based on an e-questionnaire with 42 items on the content of self-management education of COPD patients.,Setting: The study sample included all public SHC units with pulmonary outpatient clinics (n = 29) and nine out of 160 health centres in Finland.,Subjects: 83 doctors and 162 nurses.,Main outcome measures: The respondents’ answers on how regularly they included the contents regarded as essential for COPD patients’ self-management in their education of COPD patients.,Results: COPD patients were educated regularly on medical issues regarding COPD treatment, such as smoking cessation, exercise and pharmacological treatment.,However, issues vital for coping with the disease, such as psychological well-being, stress management or fatigue, were often ignored.,Patient education in SHC seemed to be more systematic than education in PHC.,The education provided by the asthma/COPD nurses (n = 70) was more systematic than the education provided by the other nurses (n = 84).,Conclusion: Healthcare professionals’ continuous education should cover not only the medical but also the psychosocial aspects of coping with COPD.,The role of doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education.,Training asthma/COPD nurses and promoting specialised nurse-led asthma/COPD clinics in primary care could be beneficial while improving practices of patient education that enhance patients’ ability to cope with the disease.KEY POINTSIssues vital for coping with chronic obstructive pulmonary disease (COPD), such as psychological well-being, stress and fatigue, are irregularly included in self-management education both in primary and specialised healthcare.Patient education provided by asthma/COPD nurses is more regular than patient education provided by other nurses.The distribution of work between doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education.,Issues vital for coping with chronic obstructive pulmonary disease (COPD), such as psychological well-being, stress and fatigue, are irregularly included in self-management education both in primary and specialised healthcare.,Patient education provided by asthma/COPD nurses is more regular than patient education provided by other nurses.,The distribution of work between doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education. | 1 |
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | The overlap between asthma and chronic obstructive pulmonary disease (COPD) is an important clinical phenomenon.,However, the prevalence of asthma-COPD overlap syndrome (ACOS) is not known.,To investigate the prevalence of ACOS among asthmatic patients with a smoking history, and evaluate the factors predicting ACOS in this patient group.,We investigated 190 primary care asthma patients with no previous diagnosis of COPD, but who were either current or ex-smokers, with a smoking history of at least 10 pack-years.,Spirometry was performed on all the patients while they were taking their normal asthma medication.,Patients were considered to have ACOS if their postbronchodilator forced expiratory volume in 1 s/forced vital capacity was <0.70.,Fifty-two (27.4%) of the patients were found to have ACOS.,Age ⩾60 years and smoking for ⩾20 pack-years were the best predictors of ACOS.,If both of these criteria were met, the odds ratio (95% confidence interval) for ACOS was 6.08 (2.11-17.49), compared with the situation where neither of these criteria were fulfilled.,There is a high prevalence of ACOS among primary health care asthmatics with a positive smoking history but no previous diagnosis of COPD.,In this population, age over 60 years and a smoking history of more than 20 pack-years were the best predictors of ACOS. | 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. | To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations.,Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010-December 2014) period were prospectively included.,Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after.,After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005).,These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed.,No pre-post differences were detected in the number of exacerbations not requiring admission.,Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA.,Clinical trials with a larger number of patients are needed in order to confirm these results. | 1 |
Mobile health (mHealth) technology is an increasingly recognized and effective method for disease management and has the potential to intervene in pulmonary function, exacerbation risk, and psychological status of patients with chronic obstructive pulmonary disease (COPD).,This study aimed to investigate the feasibility of an mHealth-based COPD management system designed for Chinese remote areas with many potential COPD patients but limited medical resources.,The system was implemented based on a tailored closed-loop care pathway that breaks the heavy management tasks into detailed pieces to be quantified and executed by computers.,Low-cost COPD evaluation and questionnaire-based psychological intervention are the 2 main characteristics of the pathway.,A 6-month prospective observational study at the community level was performed to evaluate the effect of the system.,Primary outcomes included changes in peak expiratory flow values, quality of life measured using the COPD assessment test scale, and psychological condition.,Acute exacerbations, compliance, and adverse events were also measured during the study.,Compliance was defined as the ratio of the actual frequency of self-monitoring records to the prescribed number.,A total of 56 patients was enrolled; 39 patients completed the 6-month study.,There was no significant difference in the mean peak expiratory flow value before and after the 6-month period (366.1, SD 106.7 versus 313.1, SD 116.6; P=.11).,Psychological condition significantly improved after 6 months, especially for depression, as measured using the Patient Health Questionnaire-9 scale (median 6.0, IQR 3.0-9.0 versus median 4.0, IQR 0.0-6.0; P=.001).,The COPD assessment test score after 6 months of intervention was also lower than that at the baseline, and the difference was significant (median 4.0, IQR 1.0-6.0 versus median 3.0, IQR 0.0-6.0; P=.003).,The median overall compliance was 91.1% (IQR 67%-100%).,In terms of acute exacerbation, 110 exacerbations were detected and confirmed by health care providers (per 6 months, median 2.0, IQR 1.0-5.0).,Moreover, 72 adverse events occurred during the study, including 1 death, 19 hospitalizations, and 52 clinic visits due to persistent respiratory symptoms.,We designed and validated a feasible mHealth-based method to manage COPD in remote Chinese areas with limited medical resources.,The proposed closed-loop care pathway was effective at the community level.,Proper education and frequent communication with health care providers may encourage patients’ acceptance and use of smartphones to support COPD self-management.,In addition, WeChat might play an important role in improving patient compliance and psychological distress.,Further research might explore the effect of such systems on a larger scale and at a higher evidence level. | In Denmark, the treatment of COPD is mainly managed by general practitioners (GPs).,Pulmonary rehabilitation (PR) is available to patients with COPD in the local community by GP referral, but in practice, many patients do not participate in rehabilitation.,The aim of our study was to explore 1) GPs’ perceptions of their role and responsibility in the rehabilitation of patients with COPD, and 2) GPs’ perceptions of how patients manage their COPD.,The study was based on a qualitative design with semi-structured key-informant interviews with GPs.,Investigator triangulation was applied during data generation, and analysis was done using thematic analysis methodology.,Our main findings were that GPs relied on patients themselves to take the initiative to make clinic appointments and on professionals at health centers to provide the PR including consultations on lifestyle changes.,The GPs experienced that patients chose to come to the clinic when they were in distress and that patients either declined or had poor adherence to rehabilitation when offered.,The GPs were relieved that the health centers had taken over the responsibility of rehabilitation as GPs lacked the resources to discuss rehabilitation and follow up on individual plans.,Our study suggested a potential self-reinforcing problem with the treatment of COPD being mainly focused on medication rather than on PR.,Neither GPs nor patients used a proactive approach.,Further, GPs were not fully committed to discuss non-pharmacological treatment and perceived the patients as unmotivated for PR.,As such, there is a need for optimizing non-pharmacological treatment of COPD and in particular the referral process to PR. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of death worldwide, and poses a substantial economic and social burden.,Telemonitoring has been proposed as a solution to this growing problem, but its impact on patient outcome is equivocal.,This randomized controlled trial aimed to investigate effectiveness of telemonitoring in improving COPD patient outcome.,In total, 106 subjects were randomly assigned to the telemonitoring (n = 53) or usual care (n = 53) group.,During the two months following discharge, telemonitoring group patients had to report their symptoms daily using an electronic diary.,The primary outcome measure was time to first re-admission for COPD exacerbation within six months of discharge.,During the follow-up period, time to first re-admission for COPD exacerbation was significantly increased in the telemonitoring group than in the usual care group (p = 0.026).,Telemonitoring was also associated with a reduced number of all-cause re-admissions (0.23 vs.,0.68/patient; p = 0.002) and emergency room visits (0.36 vs.,0.91/patient; p = 0.006).,In conclusion, telemonitoring intervention was associated with improved outcomes among COPD patients admitted for exacerbation in a country characterized by a small territory and high accessibility to medical services.,The findings are encouraging and add further support to implementation of telemonitoring as part of COPD care. | Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results.,Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD.,Patients with severe COPD at high risk of exacerbations were eligible for the study.,Of 560 eligible patients identified, 279 (50%) declined to participate.,The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period.,TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups received standard care.,The primary outcome was number of hospital admissions for exacerbation of COPD during the study period.,Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second <50%pred in 86% and ≥hospital admission for COPD in the year prior to enrollment in 45%, respectively, of the patients).,No difference in drop-out rate and mortality was found between the groups.,With regard to the primary outcome, no significant difference was found in hospital admissions for COPD between the groups (P=0.74), and likewise, no difference was found in time to first admission or all-cause hospital admissions.,Compared with the control group, TM group patients had more moderate exacerbations (ie, treated with antibiotics/corticosteroid, but not requiring hospital admission; P<0.001), whereas the control group had more visits to outpatient clinics (P<0.001).,Our study of patients with severe COPD showed that TM including video consultations as add-on to standard care did not reduce hospital admissions for exacerbated COPD, but TM may be an alternative to visits at respiratory outpatient clinics.,Further studies are needed to establish the optimal role of TM in the management of severe COPD. | 1 |
This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.,A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed.,Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment.,Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.,ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead.,Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period.,The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs.,0.53, p < 0.001).,Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs.,0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs.,0.12, p = 0.03).,Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators.,ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics. | Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide.,There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder.,However, additional research is required to improve our knowledge of these relationships and their possible implications.,In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD.,We conducted a cohort study in patients from the Taiwan Longitudinal Health Insurance Database between 2000 and 2013.,Patients with COPD were identified and assessed for pre-existing and incident DM.,A Cox proportional hazards model was built to identify factors associated with incident DM and to explore the prognostic effects of DM on COPD patients.,A propensity score method was used to match COPD patients with incident DM to controls without incident DM.,Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010-1.532] for mortality than that of the COPD patients without pre-existing DM.,During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363-2.403), cerebrovascular disease (HR, 1.517; 95% CI, 1.146-2.008) and coronary artery disease (HR, 1.408; 95% CI 1.089-1.820) were significant factors associated with incident DM.,Survival was worse for the COPD patients with incident DM than for the matched controls without incident DM (Log-rank, p = 0.027).,DM, either pre-existing or incident, was associated with worse outcomes in COPD patients.,Targeted surveillance and management of DM may be important in clinical care of the COPD population. | 1 |
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