a stringlengths 138 8.15k | b stringlengths 138 8.15k | label int64 1 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. | Several feasibility studies show promising results of telehealthcare on health outcomes and health-related quality of life for patients suffering from chronic obstructive pulmonary disease, and some of these studies show that telehealthcare may even lower healthcare costs.,However, the only large-scale trial we have so far - the Whole System Demonstrator Project in England - has raised doubts about these results since it conclude that telehealthcare as a supplement to usual care is not likely to be cost-effective compared with usual care alone.,The present study is known as ‘TeleCare North’ in Denmark.,It seeks to address these doubts by implementing a large-scale, pragmatic, cluster-randomized trial with nested economic evaluation.,The purpose of the study is to assess the effectiveness and the cost-effectiveness of a telehealth solution for patients suffering from chronic obstructive pulmonary disease compared to usual practice.,General practitioners will be responsible for recruiting eligible participants (1,200 participants are expected) for the trial in the geographical area of the North Denmark Region.,Twenty-six municipality districts in the region define the randomization clusters.,The primary outcomes are changes in health-related quality of life, and the incremental cost-effectiveness ratio measured from baseline to follow-up at 12 months.,Secondary outcomes are changes in mortality and physiological indicators (diastolic and systolic blood pressure, pulse, oxygen saturation, and weight).,There has been a call for large-scale clinical trials with rigorous cost-effectiveness assessments in telehealthcare research.,This study is meant to improve the international evidence base for the effectiveness and cost-effectiveness of telehealthcare to patients suffering from chronic obstructive pulmonary disease by implementing a large-scale pragmatic cluster-randomized clinical trial.,Clinicaltrials.gov, http://NCT01984840, November 14, 2013. | 1 |
Few studies have investigated the chronic obstructive pulmonary disease (COPD) mortality fraction attributable to air pollution and modification by individual characteristics of air pollution effects.,We applied distributed lag non-linear models to assess the associations between air pollution and COPD mortality in 2007-2011 in Guangzhou, China, and the total COPD mortality fraction attributable to air pollution was calculated as well.,We found that an increase of 10 μg/m3 in particulate matter with an aerodynamic diameter of 10 μm or less (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was associated with a 1.58% (95% confidence interval (CI): 0.12-3.06%), 3.45% (95% CI: 1.30-5.66%) and 2.35% (95% CI: 0.42-4.32%) increase of COPD mortality over a lag of 0-15 days, respectively.,Greater air pollution effects were observed in the elderly, males and residents with low educational attainment.,The results showed 10.91% (95% CI: 1.02-9.58%), 12.71% (95% CI: 5.03-19.85%) and 13.38% (95% CI: 2.67-22.84%) COPD mortality was attributable to current PM10, SO2 and NO2 exposure, respectively.,In conclusion, the associations between air pollution and COPD mortality differed by individual characteristics.,There were remarkable COPD mortality burdens attributable to air pollution in Guangzhou. | Reports regarding gender-related differences in COPD expression have provided conflicting results.,In the French Initiatives BPCO real-world cohort, which contained 688 patients (146 women) when data were extracted, women were matched with men (1:3 ratio: n = 107:275) on age (5-year intervals) and FEV1 (5% predicted intervals) and comparisons were performed using univariate logistic regressions.,For a given age and level of airflow obstruction, women with COPD had higher BOD scores due to more pronounced dyspnea and lower BMI, suggesting worse prognosis, and were more likely to exhibit anxiety, suggesting the need for specific assessment and care. | 1 |
Respiratory infections are well-known triggers of chronic respiratory diseases.,Recently, culture-independent tools have indicated that lower airway microbiota may contribute to pathophysiologic processes associated with asthma and chronic obstructive pulmonary disease (COPD).,However, the relationship between upper airway microbiota and chronic respiratory diseases remains unclear.,This study was undertaken to define differences of microbiota in the oropharynx of asthma and COPD patients relative to those in healthy individuals.,To account for the qualitative and quantitative diversity of the 16S rRNA gene in the oropharynx, the microbiomes of 18 asthma patients, 17 COPD patients, and 12 normal individuals were assessed using a high-throughput next-generation sequencing analysis.,In the 259,572 total sequence reads, α and β diversity measurements and a generalized linear model revealed that the oropharynx microbiota are diverse, but no significant differences were observed between asthma and COPD patients.,Pseudomonas spp. of Proteobacteria and Lactobacillus spp. of Firmicutes were highly abundant in asthma and COPD.,By contrast, Streptococcus, Veillonella, Prevotella, and Neisseria of Bacteroidetes dominated in the healthy oropharynx.,These findings are consistent with previous studies conducted in the lower airways and suggest that oropharyngeal airway microbiota are important for understanding the relationships between the various parts of the respiratory tract with regard to bacterial colonization and comprehensive assessment of asthma and COPD. | This study was undertaken to determine the association between cardiac function and therapy with beta2-adrenoceptor agonists (β2-agonists), β-blockers, or β-blocker-β-agonist combination therapy in elderly male patients with chronic obstructive pulmonary disease (COPD).,This was a retrospective cohort study of 220 elderly male COPD patients (mean age 84.1 ± 6.9 years).,The patients were divided into four groups on the basis of the use of β-blockers and β2-agonists.,N-terminal fragment pro-B-type natriuretic peptide (NT pro-BNP), left ventricular ejection fraction (LVEF), and other relevant parameters were measured and recorded.,At follow-up, the primary end point was all-cause mortality.,Multiple linear regression analysis revealed no significant associations between NT pro-BNP and the use of β2-agonists (β = 35.502, P = 0.905), β-blockers (β = 3.533, P = 0.989), or combination therapy (β = 298.635, P = 0.325).,LVEF was not significantly associated with the use of β2-agonists (β = −0.360, P = 0.475), β-blockers (β = −0.411, P = 0.284), or combination therapy (β = −0.397, P = 0.435).,Over the follow-up period, 52 patients died, but there was no significant difference in mortality among the four groups (P = 0.357).,Kaplan-Meier analysis showed no significant difference among the study groups (log-rank test, P = 0.362).,After further multivariate adjustment, use of β2-agonists (hazard ratio [HR] 0.711, 95% confidence interval [CI] 0.287-1.759; P = 0.460), β-blockers (HR 0.962, 95% CI 0.405-2.285; P = 0.930), or combination therapy (HR 0.638, 95% CI 0.241-1.689; P < 0.366) were likewise not correlated with mortality.,There was no association between the use of β2-agonists, β-blockers, or β-blocker-β2-agonist combination therapy with cardiac function and all-cause mortality in elderly male COPD patients, which indicated that they may be used safely in this population. | 1 |
An important goal of chronic obstructive pulmonary disease (COPD) treatment is to reduce the frequency of exacerbations.,Some observations suggest a decline in exacerbation rates in clinical trials over time.,A more systematic understanding would help to improve the design and interpretation of COPD trials.,We performed a systematic review and meta-regression of the placebo groups in published randomized controlled trials reporting exacerbations as an outcome.,A Bayesian negative binomial model was developed to accommodate results that are reported in different formats; results are reported with credible intervals (CI) and posterior tail probabilities (pB).,Of 1114 studies identified by our search, 55 were ultimately included.,Exacerbation rates decreased by 6.7% (95% CI (4.4, 9.0); pB < 0.001) per year, or 50% (95% CI (36, 61)) per decade.,Adjusting for available study and baseline characteristics such as forced expiratory volume in 1 s (FEV1) did not alter the observed trend considerably.,Two subsets of studies, one using a true placebo group and the other allowing inhaled corticosteroids in the “placebo” group, also yielded consistent results.,In conclusion, this meta-regression indicates that the rate of COPD exacerbations decreased over the past two decades to a clinically relevant extent independent of important prognostic factors.,This suggests that care is needed in the design of new trials or when comparing results from older trials with more recent ones.,Also a considerable effect of adjunct therapy on COPD exacerbations can be assumed.,PROSPERO 2018 CRD4218118823.,The online version of this article (10.1186/s12931-019-1163-2) contains supplementary material, which is available to authorized users. | Bronchial hyperresponsiveness (BHR), sputum eosinophilia, and bronchial reversibility are often thought to be a hallmark of asthma, yet it has been shown to occur in COPD as well.,To evaluate the relationship between BHR, lung function, and airway inflammation in COPD patients.,Thirty-one, steroid-free patients with stable, mild and moderate COPD were studied.,The following tests were carried out: baseline lung function, reversibility, provocative dose of methacholine causing a 20% fall in forced expiratory volume in 1 second, a COPD symptom score, and sputum induction.,Twenty-nine patients completed the procedures.,About 41.4% had BHR, 31.0% had increased sputum eosinophils, and 37.9% had bronchial reversibility.,Some of the patients had only one of these characteristics while others had two or the three of them.,Patients with BHR had higher sputum eosinophils than patients without BHR (P=0.046) and those with sputum eosinophils ≥3% had more exacerbations in the previous year and a higher COPD symptom score than patients with sputum eosinophils <3% (P=0.019 and P=0.031, respectively).,In patients with BHR, the cumulative dose of methacholine was negatively related to the symptom score and the number of exacerbations in the previous year.,When patients with bronchial reversibility were considered, bronchodilation was positively related to sputum eosinophils.,Our study showed that BHR, sputum eosinophilia, and bronchial reversibility were not clustered in one single phenotype of COPD but could be present alone or together.,Of interest, BHR and airway eosinophilia were associated with clinical data in terms of exacerbations and symptoms.,Further investigation is needed to clarify this topic. | 1 |
Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD).,The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years.,In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up.,Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM).,Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression.,Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk.,Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function.,Malnutrition and low BMI were also associated with increased risk of hospitalization.,Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk. | COPD may impact food-related activities, such as grocery shopping, cooking, and eating.,Decreased food intake may result in an unhealthy diet, and in malnutrition, which is highly prevalent in patients with COPD.,Malnutrition is known to negatively impact clinical outcome and quality of life.,In this qualitative study, we aimed to explore strategies used to overcome food-related challenges, ie, dietary resilience, and whether these led to a healthy diet.,Furthermore, we aimed to identify the key themes of motivation for dietary resilience in patients with severe COPD.,In October 2015 to April 2016, 12 patients with severe COPD starting a pulmonary rehabilitation program were interviewed.,Qualitative description and thematic analysis were performed.,All participants mentioned the use of strategies to overcome challenges.,Key themes of motivation for dietary resilience were identified as “wanting to be as healthy as possible”, “staying independent”, and “promoting a sense of continuity and duty”.,Two out of 12 participants met the criteria for a healthy diet.,Our study showed a variety of motivational factors and strategies reported by patients with severe COPD to overcome food-related challenges.,However, the majority (n=10) of the participants did not meet the criteria for a healthy diet.,The identified key themes can be used to develop education to support patients with severe COPD to improve their diet. | 1 |
The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.,Relevant studies were identified through MEDLINE searches.,Using random effects models, summary effects of specific previous conditions were evaluated separately and combined.,Stratified analyses were conducted based on smoking status, gender, control sources and continent.,A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies).,The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22-1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies).,Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97-1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).,Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer. | 1 |
Chronic obstructive pulmonary disease (COPD) is a respiratory syndrome characterized by progressive, partially reversible airway obstruction and lung hyperinflation.,COPD has a substantial burden which is seen in both patient quality of life and healthcare costs.,One proposed method of minimizing this burden is the implementation of clinical pathways (CPWs).,CPWs aim to guide evidence-based practice and improve the interaction between health services.,They bring the best available evidence to a range of healthcare professionals by adapting evidence-based clinical guidelines to a local context and detailing the essential steps in the assessment and care of patients.,The aim of this systematic review is to synthesize existing literature on the effects of CPWs for the treatment or management of COPD.,We will screen search hits from search strategies developed for a Cochrane Effective Practice and Organisation of Care (EPOC) systematic review on the use of CPWs in primary care and a Cochrane EPOC review on the use of CPWs in hospitals.,These searches were run in a range of databases.,Studies will be screened independently by two reviewers.,All studies identified by our search strategy will be considered regardless of study design as long as they meet the operational definition for clinical pathways developed by Kinsman et al.,(BMC Medicine 8, 2010) and focus on the treatment or management of COPD.,All included studies will be evaluated for risk of bias utilizing methodologies set out by the Cochrane collaboration.,Data regarding patient, professional and systems outcomes will be extracted from all included studies.,Data will be presented in both narrative and tabular form.,The systematic review outlined in this protocol aims to identify, assess and synthesise all available evidence on the effects of CPWs regarding the treatment and management of COPD.,As a result, this review will provide an evidence base for decision makers regarding the practicality, cost effectiveness, patient benefit and best practices regarding the implementation of CPWs for the care of COPD.,The online version of this article (doi:10.1186/s13643-016-0311-8) contains supplementary material, which is available to authorized users. | Exacerbations, a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD), affect the quality of life and prognosis.,Treatment recommendations as provided in the evidence-based guidelines are not consistently followed, partly due to absence of simplified task-oriented approach to care.,In this study, we describe the development and implementation of a clinical pathway (CP) and evaluate its effectiveness in the management of COPD exacerbation.,We developed a CP and evaluated its effectiveness in a non-randomized prospective study with historical controls on patients admitted for exacerbation of COPD to Universiti Kebangsaan Malaysia Medical Centre (UKMMC).,Consecutive patients who were admitted between June 2009 and December 2010 were prospectively recruited into the CP group.,Non-CP historical controls were obtained from case records of patients admitted between January 2008 and January 2009.,Clinical outcomes were evaluated by comparing the length of stay (LOS), complication rates, readmissions, and mortality rates.,Ninety-five patients were recruited in the CP group and 98 patients were included in the non-CP historical group.,Both groups were comparable with no significant differences in age, sex and severity of COPD (p = 0.641).,For clinical outcome measures, patients in the CP group had shorter length of stay than the non-CP group (median (IQR): 5 (4-7) days versus 7 (7-9) days, p < 0.001) and 24.1% less complications (14.7% versus 38.8%, p < 0.001).,We did not find any significant differences in readmission and mortality rates.,The implementation of CP -reduced the length of stay and complication rates of patients hospitalized for acute exacerbation of COPD. | 1 |
Ambient air pollution is associated with numerous adverse health outcomes, but the underlying mechanisms are not well understood; epigenetic effects including altered DNA methylation could play a role.,To evaluate associations of long-term air pollution exposure with DNA methylation in blood, we conducted an epigenome-wide association study in a Korean chronic obstructive pulmonary disease cohort (N = 100 including 60 cases) using Illumina’s Infinium HumanMethylation450K Beadchip.,Annual average concentrations of particulate matter ≤ 10 μm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at participants’ residential addresses using exposure prediction models.,We used robust linear regression to identify differentially methylated probes (DMPs) and two different approaches, DMRcate and comb-p, to identify differentially methylated regions (DMRs).,After multiple testing correction (false discovery rate < 0.05), there were 12 DMPs and 27 DMRs associated with PM10 and 45 DMPs and 57 DMRs related to NO2.,DMP cg06992688 (OTUB2) and several DMRs were associated with both exposures.,Eleven DMPs in relation to NO2 confirmed previous findings in Europeans; the remainder were novel.,Methylation levels of 39 DMPs were associated with expression levels of nearby genes in a separate dataset of 3075 individuals.,Enriched networks were related to outcomes associated with air pollution including cardiovascular and respiratory diseases as well as inflammatory and immune responses.,This study provides evidence that long-term ambient air pollution exposure impacts DNA methylation.,The differential methylation signals can serve as potential air pollution biomarkers.,These results may help better understand the influences of ambient air pollution on human health.,The online version of this article (10.1186/s13148-019-0635-z) contains supplementary material, which is available to authorized users. | Currently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease.,However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes.,Here, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms.,Based on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits.,For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1.,For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1.,The results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits.,The online version of this article (doi:10.1186/s40246-016-0076-0) contains supplementary material, which is available to authorized users. | 1 |
The impacts of high blood eosinophil count (HBEC) at admission for COPD exacerbation on posthospitalization outcomes are still unclear.,Previous studies have focused on its associations with first readmission rates; yet, its impacts on longitudinal outcomes such as subsequent readmissions still have to be explored.,The main objective of this study is to investigate outcomes associated with HBEC following a first hospitalization for COPD exacerbation.,This is an observational cohort study design.,We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013.,Patients were stratified into the HBEC group if the blood eosinophil count at admission was ≥200 cells/µL and/or ≥2% of the total white blood cells.,With information on exact dates of subsequent hospitalizations and death, we modeled readmissions and death as states in a multi-state Markov model and estimated transition probabilities to the next states.,Sensitivity analyses were performed by varying thresholds for the definition of HBEC (≥300 cells/µL and/or ≥3%).,A total of 479 patients were included, of which 173 had HBEC.,The transition probabilities for a first readmission was 74% (95% CI, 66%-83%) for patients with HBEC vs 70% (95% CI, 63%-77%) for patients with normal blood eosinophil count (NBEC).,The transition probabilities for a second readmission were 91% (95% CI, 84%-100%) for HBEC patients in contrast with 83% (95% CI, 74%-92%) for NBEC patients.,Meanwhile, transition probability for death was lower in patients with HBEC.,The differences enlarged in sensitivity analyses with higher cutoff.,Greater blood eosinophil cell counts during a first hospitalization for COPD predict increased susceptibility to up to two readmissions.,These patients may however have a lower risk of death. | COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes. | 1 |
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. | Cardiovascular diseases, osteoporosis, and depression are identified comorbidities of chronic obstructive pulmonary disease (COPD), but there have been few reports of chronic kidney disease (CKD) as a comorbidity of COPD.,The objective of this study was to investigate the prevalence of CKD in COPD patients using estimated glomerular filtration rate (eGFR) based on creatinine (Cr) and cystatin C (Cys) levels.,The prevalence of CKD and the values of various CKD-related parameters were compared between 108 stable COPD outpatients (COPD group) and a non-COPD control group consisting of 73 patients aged 60 years or more without a history of COPD or kidney disease.,CKD was defined as an eGFR less than 60 mL/min/1.73 m2.,The Cr level was significantly higher in the COPD group, but eGFR based on serum Cr (eGFRCr) was not significantly different between the two groups (73.3±25.3 vs 79.7±15.5 mL/min/1.73 m2).,The Cys level was significantly higher and eGFR based on serum Cys (eGFRCys) was significantly lower in the COPD group (60.0±19.4 vs 74.0±13.5 mL/min/1.73 m2, P<0.0001).,The prevalence of CKD evaluated based on eGFRCr was 31% in the COPD group and 8% in the non-COPD group with an odds ratio of 4.91 (95% confidence interval, 1.94-12.46, P=0.0008), whereas the evaluated prevalence based on eGFRCys was 53% in the COPD group and 15% in the non-COPD group with an odds ratio of 6.30 (95% confidence interval, 2.99-13.26, P<0.0001), demonstrating a higher prevalence of CKD when based on eGFRCys rather than on eGFRCr.,CKD is a comorbidity that occurs frequently in COPD patients, and we believe that renal function in Japanese COPD patients should preferably be evaluated based not only on Cr but on Cr in combination with Cys. | 1 |
Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response.,Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β.,The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations.,While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable.,In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines.,The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor.,Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD.,The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit.,Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either.,Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned.,There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target.,Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC) service was implemented in the North of the Netherlands to support General Practitioners (GPs) by providing advice from pulmonologists on a systematic basis.,To evaluate the feasibility and effectiveness of this service on patient-related outcomes.,We report baseline data on 11,401 patients and follow-up data from 2,556 patients.,GPs can refer all patients with possible obstructive airway disease (OAD) to the service, which is conducted by the local laboratory.,Patients are assessed in the laboratory using questionnaires and spirometry.,Pulmonologists inspect the data through the internet and send the GP diagnosis and management advice.,A total of 11,401 patients were assessed by the service, covering almost 60% of all adult patients with projected asthma or COPD in the area.,In all, 46% (n=5,268) of the patients were diagnosed with asthma, 18% (n=2,019) with COPD and 7% (n=788) with the overlap syndrome.,A total of 740 (7%) patients were followed up after 3 months because the GP advised them to change medication.,In this group, the proportion of unstable COPD patients (Clinical COPD Questionnaire (CCQ)⩾1) decreased from 63% (n=92) at baseline to 49% (n=72).,The proportion of patients with uncontrolled asthma (Asthma Control Questionnaire (ACQ)⩾1.5) decreased from 41% (n=204) to 23% (n=115).,In all, 938 (8%) patients were followed up after 12 months.,From these patients, the proportion of unstable COPD patients (CCQ⩾1) decreased from 47% (n=115) to 44% (n=107).,The proportion of patients with uncontrolled asthma (ACQ⩾1.5) decreased from 16% (n=95) to 14% (n=85).,The AC service assessed a considerable proportion of patients with OAD in the area, improved patients’ outcomes, and is considered to be feasible and effective. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.,Induced sputum was obtained from adults with COPD (n = 22), and healthy controls (n = 29) and was processed for differential cell counts.,The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR.,Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n = 13) and healthy controls (n = 21).,Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls.,Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants.,The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups.,The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC).,Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.,The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis. | We analyzed serial concentrations of multiple inflammatory mediators from serum and induced sputum obtained from patients with stable COPD and controls.,The objective was to determine which proteins could be used as reliable biomarkers to assess COPD disease state and severity.,Forty-two subjects; 21 with stable COPD and 21 controls, were studied every 2 weeks over a 6-week period.,Serum and induced sputum were obtained at each of 3 visits and concentrations of 19 serum and 22 sputum proteins were serially assessed using multiplex immunoassays.,We used linear mixed effects models to test the distribution of proteins for an association with COPD and disease severity.,Measures of within- and between-subject coefficients of variation were calculated for each of the proteins to assess reliability of measurement.,There was significant variability in concentrations of all inflammatory proteins over time, and variability was greater for sputum proteins (median intra-subject coefficient of variation 0.58) compared to proteins measured in serum (median intra-subject coefficient of variation 0.32, P = 0.03).,Of 19 serum proteins and 22 sputum proteins tested, only serum CRP, myeloperoxidase and VEGF and sputum IL-6, IL-8, TIMP-1, and VEGF showed acceptable intra and inter-patient reliability and were significantly associated with COPD, the severity of lung function impairment, and dyspnea.,Levels of many serum and sputum biomarkers cannot be reliably ascertained based on single measurements.,Multiple measurements over time can give a more reliable and precise estimate of the inflammatory burden in clinically stable COPD patients. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life.,This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.,Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]).,These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7.,Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.,Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male).,In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05).,Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients.,Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05).,Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001).,In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05).,The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.,Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used.,Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
The aim of this study was to assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD.,A systematic literature search of randomized controlled trials published in English up to September 2017 of LABA/LAMA FDCs vs LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus, and Google Scholar.,Outcomes including forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index (TDI) scores, St George’s Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (endurance time [ET]), inspiratory capacity (IC), and rescue medication use were evaluated.,In total, 27 studies were included in the review.,LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS.,These effects were maintained over time.,Significant improvements with LABA/LAMA FDCs vs each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected.,Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority vs LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC vs the active comparators.,Rescue medication use was significantly reduced by LABA/LAMA FDCs vs the evaluated comparators.,LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs vs the monocomponents.,Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET, and IC.,So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority vs LABA, LAMA, and LABA/ICS FDCs across the evaluated outcomes.,LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety. | Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia.,This study assessed the risk of pneumonia associated with ICS in patients with COPD.,Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014).,Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed.,Patients were categorized by airflow limitation severity.,A total of 6623 patients with COPD and 48,566 controls were analyzed.,Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06).,ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS.,Asthma was an independent risk factor for pneumonia in the COPD population.,Multivariate analysis identified independent predictors of pneumonia in the overall population.,The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).,Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further. | 1 |
Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD).,We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke.,The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema.,Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages.,We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12.,Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice.,AMs with projected pseudopods were decreased in DN-MafB Tg mice.,The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice.,Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice.,Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression. | Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain.,This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.,Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects.,In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.,Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort.,Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects.,In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups.,Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.,MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression.,Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. | 1 |
COPD is often associated with cardiovascular comorbidity.,Treatment guidelines recommend therapy with bronchodilators as first choice.,We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.,In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD.,Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score.,Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout.,All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators.,Consensus decisions were taken on every value and parameter.,The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.,Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol.,Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time.,The cardiac frequency was also significantly reduced in indacaterol-treated patients.,Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea.,These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency. | Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy.,Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo.,Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0-3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire.,Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment.,Olodaterol significantly improved FEV1 area under the curve from 0-3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053-0.085 L; P<0.01), as did formoterol.,Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo.,Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo.,St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo.,No safety signals were identified from adverse-event or other safety data.,Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile. | 1 |
To obtain evidence whether the online pulmonary rehabilitation(PR) programme ‘my-PR’ is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD.,A two-arm parallel single-blind, randomised controlled trial.,The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility.,90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26).,Participants unable to use an internet-enabled device at home were excluded.,Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme.,A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR’.,The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of −40.5 m at −4.5 m with an upper 95% CI of +52.2 m.,This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (−13.7 to 43.8).,The CAT score difference in the ITT was −1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of −2.9.,The PP analysis was consistent with the ITT.,PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation.,A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and symptom scores and was safe and well tolerated. | Pulmonary rehabilitation is known to improve function and quality of life for people with chronic obstructive pulmonary disease (COPD).,However, little research has been conducted on the influence of culture on experiences of pulmonary rehabilitation.,This study examined factors influencing uptake of pulmonary rehabilitation by Māori with COPD in New Zealand.,Grounded theory nested within kaupapa Māori methodology.,Transcripts were analyzed from interviews and focus groups with 15 Māori and ten New Zealand non-Māori invited to attend pulmonary rehabilitation for COPD.,Māori participants had either attended a mainstream hospital-based program, a community-based program designed “by Māori, for Māori”, or had experienced both.,Several factors influencing uptake of pulmonary rehabilitation were common to all participants regardless of ethnicity: 1) participants’ past experiences (eg, of exercise; of health care systems), 2) attitudes and expectations, 3) access issues (eg, time, transport, and conflicting responsibilities), and 4) initial program experiences.,These factors were moderated by the involvement of family and peers, interactions with health professionals, the way information on programs was presented, and by new illness events.,For Māori, however, several additional factors were also identified relating to cultural experiences of pulmonary rehabilitation.,In particular, Māori participants placed high value on whakawhanaungatanga: the making of culturally meaningful connections with others.,Culturally appropriate communication and relationship building was deemed so important by some Māori participants that when it was absent, they felt strongly discouraged to attend pulmonary rehabilitation.,Only the more holistic services offered a program in which they felt culturally safe and to which they were willing to return for ongoing rehabilitation.,Lack of attention to cultural factors in the delivery of pulmonary rehabilitation may be a barrier to its uptake by indigenous, minority ethnic groups, such as New Zealand Māori.,Indigenous-led or culturally responsive health care interventions for COPD may provide a solution to this issue. | 1 |
Lung hyperinflation is a feature of chronic obstructive pulmonary disease (COPD) and can determine pivotal consequence on symptoms, exercise tolerance and quality of life.,Despite the relevance of assessing lung hyperinflation, there is still no single consensus as to what volume should be taken into account.,We investigate which spirometric measurement is more reliable in assessing static lung hyperinflation and which is more related with impulse oscillometry system (IOS) measurements in COPD.,Fifty-five COPD patients were enrolled.,TLC, RV and RV:TLC ratio were obtained both with helium and plethysmography techniques.,IOS measurements (X5, Fres and R5-R20) were performed.,Pearson and Spearman correlation determined the relationships between the functional parameters that evaluate static hyperinflation (RV: TLC, TLC, RV) and IOS measurements.,As expected, we reported a statistically significant difference between these two techniques in terms of mean percentage values of TLC (7.57 ± 3.26 L; p= 0.02) and RV (15.24 ± 7.51 L; p=0.04), while RV:TLC measured with the two methods was similar (5.21 ± 4.69%; p=0.27).,The correlation analysis showed that IOS parameters, such as difference in resistance between 5 Hz and 20 Hz (R(5-20)) and resonant frequency (Fres), were positively correlated with RV:TLC ratio, while reactance at 5 Hz (X(5)) was negatively correlated with it.,In particular, we pointed out a weak correlation between RV:TLC (%) (Pleth) and R(5-20) (r=0.3, p=0.04), Fres (r=0.3; p=0.03), while X5 had a mild correlation with RV:TLC (%) (r=−0.5;p<0.0001).,Moreover, we noticed a strong relationship between RV:TLC (%)(He) and X5 (r=−0.7; p=0.0001) and a mild correlation between RV:TLC (%) (He) and Fres (r=0.4; p=0.003).,Between R5-R20 and RV:TLC, there was a weak correlation (r=0.3; p=0.001).,No correlation between TLC, RV (L,%) (both helium and Pleth derived) and IOS parameters (R(5-20), X5, Fres) was found.,RV:TLC can represent the most reliable parameter in the assessment of hyperinflation, considering the absence of significant difference in its measurement between the two techniques.,IOS provides supplementary information in the assessment of static hyperinflation. | The traditional classification of COPD, which relies solely on spirometry, fails to account for the complexity and heterogeneity of the disease.,Phenotyping is a method that attempts to derive a single or combination of disease attributes that are associated with clinically meaningful outcomes.,Deriving phenotypes entails the use of cluster analyses, and helps individualize patient management by identifying groups of individuals with similar characteristics.,We aimed to systematically review the literature for studies that had derived such phenotypes using unsupervised methods.,Two independent reviewers systematically searched multiple databases for studies that performed validated statistical analyses, free of definitive pre-determined hypotheses, to derive phenotypes among patients with COPD.,Data were extracted independently.,9156 citations were retrieved, of which, 8 studies were included.,The number of subjects ranged from 213 to 1543.,Most studies appeared to be biased: patients were more likely males, with severe disease, and recruited in tertiary care settings.,Statistical methods used to derive phenotypes varied by study.,The number of phenotypes identified ranged from 2 to 5.,Two phenotypes, with poor longitudinal health outcomes, were common across multiple studies: young patients with severe respiratory disease, few cardiovascular co-morbidities, poor nutritional status and poor health status, and a phenotype of older patients with moderate respiratory disease, obesity, cardiovascular and metabolic co-morbidities.,The recognition that two phenotypes of COPD were often reported may have clinical implications for altering the course of the disease.,This review also provided important information on limitations of phenotype studies in COPD and the need for improvement in future studies.,The online version of this article (doi:10.1186/s12931-015-0208-4) contains supplementary material, which is available to authorized users. | 1 |
Rationale: Although clinical trials have found that pulmonary rehabilitation (PR) can reduce the risk of readmissions after hospitalization for a chronic obstructive pulmonary disease (COPD) exacerbation, less is known about PR’s impact in routine clinical practice.,Objectives: To evaluate the association between initiation of PR within 90 days of discharge and rehospitalization(s).,Methods: We analyzed a retrospective cohort of Medicare beneficiaries (66 years of age or older) hospitalized for COPD in 2014 who survived at least 30 days after discharge.,Measurements and Main Results: We used propensity score matching and estimated the risk of recurrent all-cause rehospitalizations at 1 year using a multistate model to account for the competing risk of death.,Of 197,376 total patients hospitalized in 4,446 hospitals, 2,721 patients (1.5%) initiated PR within 90 days of discharge.,Overall, 1,534 (56.4%) patients who initiated PR and 125,720 (64.6%) who did not were rehospitalized one or more times within 1 year of discharge.,In the propensity-score-matched analysis, PR initiation was associated with a lower risk of readmission in the year after PR initiation (hazard ratio, 0.83; 95% confidence interval, 0.77-0.90).,The mean cumulative number of rehospitalizations at 1 year was 0.95 for those who initiated PR within 90 days and 1.15 for those who did not (P < 0.001).,Conclusions: After hospitalization for COPD, Medicare beneficiaries who initiated PR within 90 days of discharge experienced fewer rehospitalizations over 1 year.,These results support findings from randomized controlled clinical trials and highlight the need to identify effective strategies to increase PR participation. | COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions. | 1 |
It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens.,This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time.,We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015.,DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs).,In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population.,DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease.,The burden of disease showed a consistently increasing trend from 2007 to 2015.,Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs.,The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007.,As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner.,The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea. | Forced expiratory volume in 1s/forced expiratory volume in 6 s ( FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work up of subjects who are suspected of having COPD in primary care.,To determine the diagnostic accuracy of a negative pre-bronchodilator (BD) microspirometry test relative to a full diagnostic spirometry test in subjects in whom general practitioners (GPs) suspect airflow obstruction.,Cross-sectional study in which the order of microspirometry and diagnostic spirometry tests was randomised.,Study subjects were (ex-)smokers aged ⩾50 years referred for diagnostic spirometry to a primary care diagnostic centre by their GPs.,A pre-BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC<lower limit of normal (LLN) from diagnostic spirometry.,One hundred and four subjects were analysed (59.6% males, 42.3% current smokers).,Negative predictive values from microspirometry for airflow obstruction based on the fixed and LLN cut-off points were 94.4% (95% confidence interval (CI), 86.4-98.5) and 96.3% (95% CI, 88.2-99.3), respectively.,In all, 18% of positive microspirometry results were not confirmed by a post-BD FEV1/FVC <0.70 and 44% of tests were false positive compared with the LLN criterion for airflow obstruction.,Pre-bronchodilator microspirometry seems to be able to reliably preselect patients for further assessment of airflow obstruction by means of regular diagnostic spirometry.,However, use of microspirometry alone would result in overestimation of airflow obstruction and should not replace regular spirometry when diagnosing COPD in primary care. | 1 |
Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | 1 |
Pulmonary rehabilitation is an important treatment for patients with Chronic Obstructive Pulmonary Disease, who are often vitamin D deficient.,As vitamin D status is linked to skeletal muscle function, we aimed to explore if high dose vitamin D supplementation can improve the outcomes of rehabilitation in Chronic Obstructive Pulmonary Disease.,This study is a post-hoc subgroup analysis of a larger randomized trial comparing a monthly dose of 100.000 IU of vitamin D with placebo to reduce exacerbations.,50 Subjects who followed a rehabilitation program during the trial are included in this analysis.,We report changes from baseline in muscle strength and exercise performance between both study arms after 3 months of rehabilitation.,Vitamin D intervention resulted in significantly higher median vitamin D levels compared to placebo (51 [44-62] ng/ml vs 15 [13-30] ng/ml; p < 0.001).,Patients receiving vitamin D had significantly larger improvements in inspiratory muscle strength (-11±12 cmH2O vs 0±14 cmH2O; p = 0.004) and maximal oxygen uptake (110±211 ml/min vs -20±187 ml/min; p = 0.029).,Improvements in quadriceps strength (15±16 Nm) or six minutes walking distance (40±55 meter) were not significantly different from the effects in the placebo group (7±19 Nm and 11±74 meter; p>0.050).,High dose vitamin D supplementation during rehabilitation may have mild additional benefits to training. | COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | 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. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
to evaluate the concurrent validity of the six-minute step test (6MST) in assessing exercise capacity of COPD patients using the six-minute walk test (6MWT) as a gold-standard.,The predictive validity of the 6MST was assessed to determine a cut-off point for identification of low exercise capacity.,thirty-two COPD patients (50-87 years old) with mild to very severe obstruction performed the 6MST and 6MWT twice.,Concurrent validity: a strong positive correlation (Pearson) between the number of ascents on the first (T1), second (T2) and the best of both (T1 or T2) tests during the 6MWT was observed.,Although a moderate negative correlation with BODE index and FEV1 was found, it was considered insufficient to test the validity, therefore ROC curves were not applied.,The predictive validity (ROC) of the 6MST to identify low physical capacity (compared with the 6MWT) using the performance of T1 or T2, or solely T1 was considered accurate, and the area under the curve was 0.8 (IC95% 0.62-0.98) and 0.85 (IC95% 0.70-0.99), respectively.,To classify patients, the cut-off points of 86 and 78 steps were chosen, with both values showing 90% of sensitivity and specificity of 64% and 68% for T1 or T2, or solely T1, respectively.,The number of steps on the 6MST was valid to verify exercise capacity in COPD patients and the cut-off point of 78 steps was able to identify patients with poor exercise tolerance.,Values under this cut-off point are considered to identify patients with a poorer prognosis. | Because treadmill exercise testing is more representative of daily activity than cycle testing, we developed treadmill protocols to be used in various clinical settings as part of a two-year, multicenter, chronic obstructive pulmonary disease (COPD) trial evaluating the effect of tiotropium on exercise.,We enrolled 519 COPD patients aged 64.6 ± 8.3 years with a postbronchodilator forced expiratory volume in one second (FEV1) of 1.25 ± 0.42 L, 44.3% ± 11.9% predicted.,The patients performed symptom-limited treadmill tests where work rate (Ẇ) was increased linearly using speed and grade adjustments every minute.,On two subsequent visits, they performed constant Ẇ tests to exhaustion at 90% of maximum Ẇ from the incremental test.,Mean incremental test duration was 522 ± 172 seconds (range 20-890), maximum work rate 66 ± 34 watts.,For the first and second constant Ẇ tests, both at 61 ± 33 watts, mean endurance times were 317 ± 61 seconds and 341 ± 184 seconds, respectively.,The mean of two tests had an intraclass correlation coefficient of 0.85 (P < 0.001).,During the second constant Ẇ test, 88.2% of subjects stopped exercise because of breathing discomfort; 87.1% for Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II, 88.5% for GOLD Stage III, and 90.2% for GOLD Stage IV.,The symptom-limited incremental and constant work treadmill protocol was well tolerated and appeared to be representative of the physiologic limitations of COPD. | 1 |
In the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk.,However, many patients were not taking triple therapy before study participation.,This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.,The effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis.,Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.,Overall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening.,Baseline characteristics were generally similar between groups.,Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89-1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94-1.19]).,However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81-1.41] (≥100 cells/μL) to 1.45 [0.58-3.60] (≥400 cells/μL).,Consistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening.,Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/q_gF6ypMYJw | Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD.,Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.,Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017.,Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.,Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events).,In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively).,In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%.,Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events.,Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment. | 1 |
Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status. | 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 |
Changes in physical activity (PA) are difficult to interpret because no framework of minimal important difference (MID) exists.,We aimed to determine the minimal important difference (MID) in physical activity (PA) in patients with Chronic Obstructive Pulmonary Disease and to clinically validate this MID by evaluating its impact on time to first COPD-related hospitalization.,PA was objectively measured for one week in 74 patients before and after three months of rehabilitation (rehabilitation sample).,In addition the intraclass correlation coefficient was measured in 30 patients (test-retest sample), by measuring PA for two consecutive weeks.,Daily number of steps was chosen as outcome measurement.,Different distribution and anchor based methods were chosen to calculate the MID.,Time to first hospitalization due to an exacerbation was compared between patients exceeding the MID and those who did not.,Calculation of the MID resulted in 599 (Standard Error of Measurement), 1029 (empirical rule effect size), 1072 (Cohen's effect size) and 1131 (0.5SD) steps.day-1.,An anchor based estimation could not be obtained because of the lack of a sufficiently related anchor.,The time to the first hospital admission was significantly different between patients exceeding the MID and patients who did not, using the Standard Error of Measurement as cutoff.,The MID after pulmonary rehabilitation lies between 600 and 1100 steps.day-1.,The clinical importance of this change is supported by a reduced risk for hospital admission in those patients with more than 600 steps improvement. | There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | 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. | 1 |
The current mainstay of therapy for chronic obstructive pulmonary disease (COPD) is long-acting bronchodilators.,To date, the effect of indacaterol, a β2-agonist, on activities of daily living in COPD patients is not well understood.,The aim of this study was to evaluate the efficacy of indacaterol with regard to activities of daily living in patients with COPD.,In this nonrandomized open-label study, 23 patients with COPD were instructed to carry an accelerometer for 4 weeks without indacaterol therapy and then for another period of 4 weeks while receiving indacaterol therapy.,The number of steps, duration of moderate or greater physical activity, and energy expenditure were significantly increased after treatment with indacaterol compared with baseline data in all patients with COPD; the metabolic equivalent of task was also significantly enhanced after treatment with indacaterol.,This study provides early evidence that indacaterol improves daily physical activity in patients with COPD. | Indacaterol is a novel, inhaled once-daily ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD).,This study compared the onset of action of single doses of indacaterol 150 and 300 μg with salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo in moderate-to-severe COPD patients.,This was a multicenter, randomized, double-blind, placebo-controlled crossover study.,The primary variable was forced expiratory volume in one second (FEV1) at five minutes postdose.,Out of 89 patients randomized (mean age 62 years), 86 completed the study.,At five minutes postdose, both indacaterol doses were statistically and clinically superior to placebo (P < 0.001), with treatment-placebo differences in FEV1 of 100 (95% confidence interval [CI] 70-130) mL and 120 (95% CI 90-150) mL for indacaterol 150 and 300 μg, respectively.,FEV1 at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol (10 and 30 mL for indacaterol 150 and 300 μg, respectively) and significantly higher than for salmeterol-fluticasone (50 mL, P = 0.003; 70 mL, P < 0.001, respectively).,Moreover, both indacaterol doses showed significantly higher FEV1 than placebo (P < 0.001) at all postdose time points.,The numbers of patients with an FEV1 increase of at least 12% and 200 mL at five minutes postdose were 16 (18.8%), 24 (27.6%), 20 (23.3%), 8 (9.1%), and 3 (3.4%) for indacaterol 150 and 300 μg, salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo, respectively.,Single doses of indacaterol 150 and 300 μg demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol-fluticasone. | 1 |
Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment.,Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD.,To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied.,Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg).,COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT).,Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects.,The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO.,Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT.,In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024).,We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction. | Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible.,In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease.,Development of hyperinflation during the course of COPD is insidious.,Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation.,Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease.,Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD.,The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD.,We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease. | 1 |
Exercise tolerance is an important endpoint in chronic obstructive pulmonary disease (COPD) clinical trials.,Little is known about the comparative measurement properties of constant work rate cycle ergometry (CWRCE) and the endurance shuttle walking test (ESWT).,The objective of this sub-analysis of the TORRACTO® study was to directly compare the endurance measurement properties of CWRCE and ESWT in patients with COPD in a multicentre, multinational setting.,We predicted that both tests would be similarly reliable, but that the ESWT would be more responsive to bronchodilation than CWRCE.,This analysis included 151 patients who performed CWRCE and ESWT at baseline and week 6 after receiving once-daily placebo, tiotropium/olodaterol (T/O) 2.5/5 μg or T/O 5/5 μg.,Reproducibility was assessed by comparing their respective performance at baseline and week 6 in the placebo group.,Responsiveness to bronchodilation was assessed by comparing endurance time at week 6 with T/O with baseline values and placebo.,The locus of symptom limitation and end-exercise Borg scales for breathing and leg discomfort for both tests were also analysed.,The intraclass correlation coefficients for CWRCE and ESWT were 0.56 [95% confidence interval (CI) 0.37-0.71] and 0.75 (95% CI 0.63-0.84).,More patients were limited by breathing discomfort during the ESWT than during CWRCE, whereas more patients were limited by leg discomfort or breathing/leg discomfort during CWRCE than the ESWT (p <0.0001).,Both tests were responsive to bronchodilator treatment: there was a 19% increase in endurance time from baseline at week 6 (p = 0.0006) assessed with CWRCE, and a 20% increase in endurance time assessed with ESWT (p = 0.0013).,Both exercise tests performed well in a multicentre clinical trial.,Although the locus of symptom limitation differed between the two tests, both were reliable and responsive to bronchodilation.,For future clinical trials, the choice of test should depend on the study requirements.,NCT01525615.,The reviews of this paper are available via the supplemental material section. | Chronic obstructive pulmonary disease (COPD) constitutes a growing health care problem worldwide.,Integrated disease management (IDM) of mild to moderate COPD patients has been demonstrated to improve exercise capacity and health status after one year, but long-term results are currently lacking in primary care.,Long-term data from the Bocholtz study, a controlled clinical trial comparing the effects of IDM versus usual care on health status in 106 primary care COPD patients during 24 months of follow-up, were analyzed using the Clinical COPD Questionnaire (CCQ).,In addition, the Kroonluchter IDM implementation program has treated 216 primary care patients with mild to moderate COPD since 2006.,Longitudinal six-minute walking distance (6MWD) results for patients reaching 24 months of follow-up were analyzed using paired-sample t-tests.,In prespecified subgroup analyses, the differential effects of baseline CCQ score, Medical Research Council (MRC) dyspnea score, and 6MWD were investigated.,In the Bocholtz study, subjects were of mean age 64 years, with an average postbronchodilator forced expiratory volume in one second (FEV1) of 63% predicted and an FEV1/forced vital capacity (FVC) ratio of 0.56.,No significant differences existed between groups at baseline.,CCQ improved significantly and in a clinically relevant manner by 0.4 points over 24 months; effect sizes were doubled in patients with CCQ > 1 at baseline and tripled in patients with MRC dyspnea score >2.,In the Kroonluchter cohort, 56 subjects completed follow-up, were of mean age 69 years, with an FEV1/FVC ratio of 0.59, while their postbronchodilator FEV1 of 65% predicted was somewhat lower than in the total group.,6MWD improved significantly and in a clinically relevant manner up to 93 m at 12 months and was sustained at 83 m over 24 months; this effect occurred faster in patients with MRC dyspnea score >2.,In patients with baseline 6MWD < 400 m the improvement remained >100 m at 24 months.,In this study, IDM improved and sustained health status and exercise capacity in primary care COPD patients during two years of follow-up.,Improvements in health status are consistently higher in patients with CCQ > 1 at baseline, being strongest in patients with baseline MRC dyspnea score >2.,Improvements in exercise capacity remain highest in patients with 6MWD < 400 m at baseline and seem to occur earlier in patients with MRC dyspnea score >2. | 1 |
Acute exacerbations are the major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD).,Rhinovirus, which causes acute exacerbations may also accelerate progression of lung disease in these patients.,Current therapies reduces the respiratory symptoms and does not treat the root cause of exacerbations effectively.,We hypothesized that quercetin, a potent antioxidant and anti-inflammatory agent with antiviral properties may be useful in treating rhinovirus-induced changes in COPD.,Mice with COPD phenotype maintained on control or quercetin diet and normal mice were infected with sham or rhinovirus, and after 14 days mice were examined for changes in lung mechanics and lung inflammation.,Rhinovirus-infected normal mice showed no changes in lung mechanics or histology.,In contrast, rhinovirus-infected mice with COPD phenotype showed reduction in elastic recoiling and increase in lung inflammation, goblet cell metaplasia, and airways cholinergic responsiveness compared to sham-infected mice.,Interestingly, rhinovirus-infected mice with COPD phenotype also showed accumulation of neutrophils, CD11b+/CD11c+ macrophages and CD8+ T cells in the lungs.,Quercetin supplementation attenuated rhinovirus-induced all the pathologic changes in mice with COPD phenotype.,Together these results indicate that quercetin effectively mitigates rhinovirus-induced progression of lung disease in a mouse model of COPD.,Therefore, quercetin may be beneficial in the treatment of rhinovirus-associated exacerbations and preventing progression of lung disease in COPD. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity.,Intercostal muscle ultrasound offers a repeatable and radiation-free alternative, however requires validation.,We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters.,Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2nd and 3rd parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT.,Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91.,Inter-rater ICC was fair to excellent.,Ultrasound intercostal thickness moderately correlated with FEV1% predicted (r = 0.33) and quadriceps thickness (r = 0.31).,Echogenicity correlated negatively with FEV1% predicted (r = −0.32).,CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness.,These data confirm ultrasound of parasternal intercostal musculature is reproducible.,Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity.,This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics.,The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall. | A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters.,However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD.,A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated.,The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients.,Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein.,There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030).,Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003).,Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation.,No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873).,These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients. | 1 |
Comorbidities adversely affect the quality of life and survival of patients with chronic obstructive pulmonary disease (COPD), and timely identification and management of comorbidities are important in caring for COPD patients.,This study aimed to investigate the impact of COPD on long-term developmental trajectories of its comorbidities.,From 2010 to 2013, all spirometry-confirmed COPD patients with a 5-year follow-up period were identified as the cases.,The prevalence of comorbidities and their trajectories in COPD cases were obtained and compared with those in non-COPD controls matched for age, sex, smoking status and Charlson comorbidity index (CCI).,Over the study period, a total of 682 patients, 341 each in COPD and control groups were included, with a mean age of 69.1 years and 89% male.,The baseline mean CCI was 1.9 for both groups of patients and significantly increased to 3.4 and 2.7 in COPD and control groups after 5 years, respectively (both P < 0.001).,Through the 5-year follow-up, a significant increase in the prevalence of all comorbidities of interest was observed in the COPD cohort and the incidence was remarkably higher for hypertension [incidence rate ratio (IRR) 1.495; 95% confidence interval (CI) 1.017-2.198], malignancy (IRR 2.397; 95% CI 1.408-4.081), diabetes mellitus (IRR 2.927; 95% CI 1.612-5.318), heart failure (IRR 2.531; 95% CI 1.502-4.265) and peptic ulcer disease (IRR 2.073; 95% CI 1.176-3.654) as compared to the non-COPD matched controls.,In conclusion, our findings suggest that the presence of COPD may be considered a pathogenic factor involved in the development of certain comorbidities. | This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.,Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan.,Patients were grouped according to GOLD 2011 and 2017 guidelines respectively.,Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.,A total of 1,053 COPD patients were included.,The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively.,When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively.,Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B.,The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017.,Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017.,The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.,The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011.,A pharmacological discordance to the guidelines was identified.,Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines.,Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. | 1 |
Early identification of preventable risk factors of COPD progression is important.,Whether exacerbations have a negative impact on disease progression is largely unknown.,We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.,Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied.,Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits.,Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.,Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation.,The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year.,Patients with more years with ≥1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations.,When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).,Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies. | 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 |
The COPD Assessment Test (CAT) contains eight items (cough, phlegm, chest tightness, breathlessness, limited activities, confidence leaving home, sleeplessness and energy).,The current study aimed 1) to better understand the impact of the respiratory and non-respiratory CAT item scores on the CAT total score; and 2) to determine the impact of pulmonary rehabilitation (PR) on CAT items and CAT total score.,CAT total score of ≥10 or ≥ 18 points was used to classify patients as highly symptomatic, a decrease of 2 points was considered as clinically relevant improvement.,‘Cough’, ‘phlegm’, ‘chest tightness’, ‘breathlessness’ were defined as respiratory items; ≥3 points on each item was defined as highly symptomatic.,In total, 497 clinically stable patients (55% male, age 64.0 (57.5-71.0) years, FEV1 46.0 (32.0-63.0)% predicted, CAT total score 22.0 (17.5-26.0) points) were included. 95% had CAT score ≥ 10 points and 75% ≥18 points.,Respectively, 45% and 54% of subjects scored high on 3 or 4 of the respiratory CAT items.,Following PR, 220 patients (57.7%) reported an improved health status as assessed by CAT total score (− 3.0 (− 7.0-1.0) points).,Change in CAT item scores ranged from 0.0 (− 1.0-0.0) to − 1.0 (− 2.0-0.0) points) with best improvements in ‘energy’ (− 1.0 (− 2.0-0.0)points).,A substantial number of patients classified as highly symptomatic did not report a high level of respiratory symptoms, indicating that non-respiratory symptoms impact on disease classification and treatment algorithm.,The impact of PR on CAT item scores varied by individual item.,Netherlands National Trial Register (NTR3416).,Registered 2 May 2012.,The online version of this article (10.1186/s12955-018-1034-4) contains supplementary material, which is available to authorized users. | Chronic Obstructive Pulmonary Disease (COPD) is a worldwide public health concern.,It is also a major source of disability that is often overlooked, depriving patients of effective treatments.,This study describes the development and validation of a questionnaire specifically assessing COPD-related disability.,The DIsability RElated to COPD Tool (DIRECT) was developed according to reference methods, including literature review, patient and clinician interviews and test in a pilot study.,A 12-item questionnaire was included for finalization and validation in an observational cross-sectional study conducted by 60 French pulmonologists, who recruited 275 COPD patients of stage II, III and IV according to the GOLD classification.,Rasch modeling was conducted and psychometric properties were assessed (internal consistency reliability; concurrent and clinical validity).,The DIRECT score was built from the 10 items retained in the Rasch model.,Their internal consistency reliability was excellent (Cronbach’s alpha = 0.95).,The score was highly correlated with the Saint George’s Respiratory Questionnaire Activity score (r = 0.83) and the London Handicap Scale (r = −0.70), a generic disability measure.,It was highly statistically significantly associated to four clinical parameters (P < 0.001): GOLD classification, BODE index, FEV1 and 6-minute walk distance.,DIRECT is a promising tool that could help enhance the management of COPD patients by integrating an evaluation of the COPD-related disability into daily practice. | 1 |
COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning.,The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation.,Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study.,A clinical symptom questionnaire was completed by patients at baseline.,In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment.,The most frequently reported COPD symptom was breathlessness (90.8%).,Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms.,The most frequently reported morning activity was getting out of bed (82.9%).,The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms.,There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment.,Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities.,These patients also have more prevalent and severe COPD symptoms.,The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally.,Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97.,A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank.,The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways.,We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications. | To determine the impact of sarcopenia and obesity on pulmonary function and quality of life (QOL) in chronic obstructive pulmonary disease (COPD) patients.,Data were obtained from the Korea National Health and Nutrition Examination Survey, including data from health interviews, health examinations, nutritional questionnaires, and laboratory findings.,Laboratory data included pulmonary function assessment and dual energy X-ray absorptiometry results.,Sarcopenia was measured by dual energy X-ray absorptiometry, and obesity was defined by body mass index.,Male COPD patients were then classified into 4 groups according to the presence of sarcopenia and obesity.,In male patients with COPD, the prevalence of sarcopenia was found to be 29.3%, and that of sarcopenic obesity was 14.2%.,Furthermore, 22.5% of the patients observed in this study had impaired QOL.,Following multivariable statistical analysis, both sarcopenia and obesity were independent risk factors for worsening lung function.,Adjusted values of forced vital capacity and forced expiratory volume in 1 second were the lowest in the sarcopenic obesity group.,Sarcopenia was also associated with more subjective activity limitation and poorer QOL; however obesity was related to less subjective limitation and better QOL after multivariable analysis.,Adjusted value of QOL was the lowest in sarcopenic subjects without obesity, and the highest in obese subject without sarcopenia.,Both sarcopenia and obesity were found to be associated with worsening lung function in male COPD patients.,However, obesity was positively correlated with improved QOL while sarcopenia was negatively correlated with QQL. | 1 |
A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression.,Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.,33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects.,A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.,In COPD, compared to no-COPD, we found a faster lung function decline at follow-up.,Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced.,Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD.,The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001).,Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03).,No correlation was found between ΔFEV1, ΔCRP and ΔWBCs.,By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.,Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression.,Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease. | Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases.,Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids.,Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers.,This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies.,In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients.,Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists.,Currently, several other novel mediator-targeted drugs are undergoing clinical trials.,As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes.,The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. | 1 |
Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases.,We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema.,We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks.,Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU).,We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli.,We also evaluated the number and the area of pores of Kohn in FUs.,We performed linear regression analysis to estimate the effect of these data on pulmonary function tests.,In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity.,A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema. | To investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer.,This was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013.,Lung function, radiology, and clinical data were retrieved.,Among all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment.,Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma.,Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients.,Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients.,Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer.,Younger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments. | 1 |
Indacaterol is an inhaled, once-daily long-acting β2-agonist bronchodilator for regular use in patients with chronic obstructive pulmonary disease (COPD).,As indacaterol is the first once-daily β2-agonist to be developed, it is relevant to evaluate its bronchodilator efficacy, safety, and tolerability.,Data were pooled from three randomized, double-blind, clinical studies in patients with moderate-to-severe COPD treated with indacaterol 150 μg qd (n = 627) or placebo (n = 1021).,Bronchodilator efficacy was assessed as trough (24-hour post-dose) forced expiratory volume in 1 second (FEV1) after 12 weeks (primary endpoint in individual studies) and FEV1 measured serially post-dose.,Rescue use of albuterol was monitored.,At week 12, indacaterol increased trough FEV1 by 160 mL compared with placebo (P < 0.001), exceeding the 120 mL level prespecified as clinically important.,FEV1 during the first 12-hour post-dose at week 12 averaged 210 mL higher with indacaterol than with placebo (P < 0.001).,Patients receiving indacaterol recorded 53% of days without use of rescue albuterol, compared with 38% of days in the placebo group (P < 0.001).,Adverse events (mostly mild or moderate) were reported for 52% and 46% of patients receiving indacaterol and placebo, respectively, and serious adverse events for 4% and 5%.,Worsening of COPD was the most frequent adverse event (10% indacaterol; 15% placebo).,Indacaterol had little effect on pulse or blood pressure or measures of systemic β2-adrenoceptor activity (blood glucose, serum potassium, and corrected QT interval).,Indacaterol was an effective bronchodilator and was well tolerated, with a good safety profile over 12 weeks of treatment.,It should prove a useful treatment for patients with moderate-to-severe COPD. | Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease (COPD).,This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD.,In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 μg, indacaterol 300 μg, tiotropium 18 μg and placebo, each once-daily for 14 days.,Each treatment period was separated by a 14-day washout.,Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators.,The primary efficacy variable was trough forced expiratory volume in one second (FEV1) at 24 h post-dose after 14 days.,The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variable.,A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed.,Trough FEV1 after 14 days with indacaterol 150 μg and 300 μg was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001).,For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 μg, respectively.,At 5 min post-dose on Day 1, the mean FEV1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indacaterol 150 and 300 μg, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001).,Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 μg and 300 μg, tiotropium and placebo treatments, respectively.,Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation.,Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing.,Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended.,ClinicalTrials.gov: NCT00615459, EudraCT number: 2007-004071-19 | 1 |
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | 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 chronic obstructive pulmonary disease (COPD) assessment test (CAT) is widely used to assess the impact of COPD symptoms on health status.,Whilst the CAT consists of eight different items, details on the distribution of each item are limited.,This study aimed to investigate the distribution and clinical implication of each CAT item, stratified by CAT severity group, in stable COPD patients.,This was a cross-sectional study at a single referral hospital in South Korea.,Spirometry confirmed COPD patients with CAT measured at the first clinical visit were retrospectively identified.,Patients were categorized into three groups: low (0 ≤ CAT < 10), medium (10 ≤ CAT < 20), and high (20 ≤ CAT ≤ 40) impact group.,For the purpose of this analysis, the first four items (cough, sputum, chest tightness, and dyspnea) and the remaining four items (activities, confidence, sleep and energy) were also grouped as “pulmonary” and “extra-pulmonary”, respectively.,A total of 815 patients were included, and mean (SD) forced expiratory volume in 1 s (FEV1) was 62.8 (17.4) % pred.,Among them, 300 patients (36.8%) were in the high impact group and had a greater exacerbation history and lower lung function.,The proportion of “extra-pulmonary” items score was greater in patients with higher total CAT scores, with the activity and confidence items showing higher scores.,In our study, in addition to dyspnea, activity limitation is a particular problem in individual patients with higher CAT total scores, for which physicians need to pay more attention.,Our study suggests that whilst CAT total score captures the overall impact of COPD, each item of the CAT contains potentially useful information in understanding the patient’s symptom burden. | To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data.,Primary care; Lothian (population approximately 800 000), Scotland.,Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record.,Patients were followed up until 2010, death or they left a participating practice.,First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care.,1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission.,Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model.,More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model.,High BMI was associated with a lower risk of first AECOPD admission and readmission.,Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission.,Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission.,The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. | 1 |
Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk.,However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed.,In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS.,Several studies sought out to determine the effects of withdrawing ICS in patients with COPD.,Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms.,However, these studies were fraught with numerous methodological limitations.,Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients.,Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol).,Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen.,Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice.,Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal.,In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are progressively limited in their ability to undertake normal everyday activities by a combination of exertional dyspnoea and peripheral muscle weakness.,COPD is characterised by expiratory flow limitation, resulting in air trapping and lung hyperinflation.,Hyperinflation increases acutely under conditions such as exercise or exacerbations, with an accompanying sharp increase in the intensity of dyspnoea to distressing and intolerable levels.,Air trapping, causing increased lung hyperinflation, can be present even in milder COPD during everyday activities.,The resulting activity-related dyspnoea leads to a vicious spiral of activity avoidance, physical deconditioning, and reduced quality of life, and has implications for the early development of comorbidities such as cardiovascular disease.,Various strategies exist to reduce hyperinflation, notably long-acting bronchodilator treatment (via reduction in flow limitation and improved lung emptying) and an exercise programme (via decreased respiratory rate, reducing ventilatory demand), or their combination.,Optimal bronchodilation can reduce exertional dyspnoea and increase a patient's ability to exercise, and improves the chance of successful outcome of a pulmonary rehabilitation programme.,There should be a lower threshold for initiating treatments appropriate to the stage of the disease, such as long-acting bronchodilators and an exercise programme for patients with mild-to-moderate disease who experience persistent dyspnoea. | 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 |
Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | The performance of daily activities is a major challenge for people with chronic obstructive pulmonary disease (COPD).,The Functional Performance Inventory (FPI) was developed based on an analytical framework of functional status and qualitative interviews with COPD patients describing these difficulties.,The 65-item FPI was reduced to a 32-item short form (SF) through a systematic process of qualitative and quantitative item reduction and formatted for greater clarity and ease of use.,This study examined the content validity of the reduced, reformatted form of the instrument, the FPI-SF.,Qualitative cognitive interviews were conducted with COPD patients recruited from three geographically diverse pulmonary clinics in the United States.,Interviews were designed to assess respondent interpretation of the instrument, evaluate clarity and ease of completion, and identify any new activities participants found important and difficult to perform that were not represented by the existing items.,Twenty subjects comprised the sample; 12 (60%) were male, 14 (70%) were Caucasian, the mean age was 63.0 ± 11.3 years, 12 (60%) were retired, the mean forced expiratory volume in 1 second (FEV1) was 1.5 ± 0.5 L, and the mean percent predicted FEV1 was 48.4% ± 13.1%.,Participants understood the FPI-SF as intended, including instructions, items, and response options.,Two minor formatting changes were suggested to improve clarity of presentation.,Participants found the content of the FPI-SF to be comprehensive, with items covering activities they felt were important and often difficult to perform.,These results, together with its development history and previously tested quantitative properties, suggest that the FPI-SF is content valid for use in clinical studies of COPD. | 1 |
Within telehealth there are a number of domains relevant to pulmonary care: telemonitoring, teleassistance, telerehabilitation, teleconsultation and second opinion calls.,In the last decade, several studies focusing on the effects of various telemanagement programs for patients with chronic obstructive pulmonary disease (COPD) have been published but with contradictory findings.,From the literature, the best telemonitoring outcomes come from programs dedicated to aged and very sick patients, frequent exacerbators with multimorbidity and limited community support; programs using third-generation telemonitoring systems providing constant analytical and decisionmaking support (24 h/day, 7 days/week); countries where strong community links are not available; and zones where telemonitoring and rehabilitation can be delivered directly to the patient’s location.,In the near future, it is expected that telemedicine will produce changes in work practices, cultural attitudes and organization, which will affect all professional figures involved in the provision of care.,The key to optimizing the use of telemonitoring is to correctly identify who the ideal candidates are, at what time they need it, and for how long.,The time course of disease progression varies from patient to patient; hence identifying for each patient a ‘correct window’ for initiating telemonitoring could be the correct solution.,In conclusion, as clinicians, we need to identify the specific challenges we face in delivering care, and implement flexible systems that can be customized to individual patients’ requirements and adapted to our diverse healthcare contexts. | An essential element in the treatment of patients with chronic obstructive pulmonary disease (COPD) is rehabilitation, of which supervised training is an important part.,However, not all individuals with severe COPD can participate in the rehabilitation provided by hospitals and municipal training centres due to distance to the training venues and transportation difficulties.,The aim of the study was to assess the feasibility of an individualized home-based training and counselling programme via video conference to patients with severe COPD after hospitalization including assessment of safety, clinical outcomes, patients’ perceptions, organisational aspects and economic aspects.,The design was a pre- and post-test intervention study.,Fifty patients with severe COPD were included.,The telemedicine training and counselling included three weekly supervised exercise sessions by a physiotherapist and up to two supervised counselling and training sessions in energy conservation techniques by an occupational therapist.,The telemedicine videoconferencing equipment was a computer containing a screen, a microphone, an on/off switch and a volume control.,Thirty seven (74%) participants completed the programme, with improvements in health status assessed by the Clinical COPD Questionnaire and physical performance assessed by a sit-to-stand test and a timed-up-and-go test.,There were no cases of patient fall or emergency contact with a general practitioner during the telemedicine training sessions.,The study participants believed the telemedicine training and counselling was essential for getting started with being physically active in a secure manner.,The business case showed that under the current financing system, the reimbursement to the hospital was slightly higher than the hospital expenditures.,Thus, the business case for the hospital was positive.,The organizational analysis indicated that the perceptions of the staff were that the telemedicine service had improved the continuity of the rehabilitation programme for the patients and enabled the patients’ everyday lives to be included in the treatment.,This study showed that home-based supervised training and counselling via video conference is safe and feasible and that telemedicine can help to ensure more equitable access to supervised training in patients with severe COPD.,Clinical Trials NCT02085187 (Date of registration 10.03.2014). | 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. | Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved.,The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth.,This research performs a narrative synthesis of the results from included studies.,Thirty-seven studies met the inclusion criteria.,Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth.,Seven barriers to, and nine facilitators of, home telehealth use were identified.,Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth.,The online version of this article (doi:10.1007/s12160-014-9607-x) contains supplementary material, which is available to authorized users. | 1 |
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. | The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression.,Therefore, preventing and treating exacerbations are major goals of COPD management.,The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD.,In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo.,In the longer trials (≥6 months’ duration) tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations.,In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization.,In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13) and/or a long-acting beta-agonist (LABA; n = 4), tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA.,The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation.,The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation.,For the management of acute exacerbations, an increase in short-acting inhaled bronchodilators is recommended as needed, while the potential role of long-acting bronchodilators, such as tiotropium, in conjunction with short-acting agents, is unclear and warrants further study. | 1 |
Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations.,Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of “clinically important deterioration” (CID) has therefore been developed.,We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies.,The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE).,All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history.,We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George’s Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death.,The time to first CID was based on the first occurrence of any of the following: a decrease of ≥100 mL from baseline in FEV1, an increase of ≥4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death.,The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death.,Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY.,In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY.,The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850. | 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 |
COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation. | Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world.,Although smoking is the main risk factor for this disease, only a minority of smokers develop COPD.,Why this happens is largely unknown.,Recent discoveries by the human microbiome project have shed new light on the importance and richness of the bacterial microbiota at different body sites in human beings.,The microbiota plays a particularly important role in the development and functional integrity of the immune system.,Shifts or perturbations in the microbiota can lead to disease.,COPD is in part mediated by dysregulated immune responses to cigarette smoke and other environmental insults.,Although traditionally the lung has been viewed as a sterile organ, by using highly sensitive genomic techniques, recent reports have identified diverse bacterial communities in the human lung that may change in COPD.,This review summarizes the current knowledge concerning the lung microbiota in COPD and its potential implications for pathogenesis of the disease. | 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. | FEV1 is universally used as a measure of severity in COPD.,Current thresholds are based on expert opinion and not on evidence.,We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.,We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS).,Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.,A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%).,Overall 975 (28.1%) patients died at 5 years.,The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%.,Survival at 5 years was 0.89 for patients with FEV1≥70 vs.,0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74).,The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001).,Prognostic reliability is maintained at 1, 3, 5, and 10 years.,In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.,The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%.,These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs. | 1 |
Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them.,On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well.,Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage.,We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema.,Patients with emphysema may differ among COPD population even in terms of cardiovascular function. | Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD.,The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients.,We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD.,All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET).,The end-expiratory lung volume (EELV) was evaluated during the CPET.,Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation.,Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%.,Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004).,Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively.,The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise.,This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function. | 1 |
Despite the severe symptoms experienced by dying COPD patients, specialized palliative care (SPC) services focus mainly on cancer patients.,We aimed to study the access to SPC that COPD and lung cancer (LC) patients receive and how that access affects the need for acute hospital care.,A descriptive regional registry study using data acquired through VAL, the Stockholm Regional Council’s central data warehouse, which covers nearly all healthcare use in the county of Stockholm.,All the patients who died of COPD or LC from 2015 to 2019 were included.,T-tests, chi-2 tests, and univariable and multivariable logistic regression analyses were performed on the accumulated data.,In total, 6479 patients, (2917 with COPD and 3562 with LC) were studied.,The patients with LC had more access to SPC during the last three months of life than did those with COPD (77% vs. 18%, respectively; p < .0001), whereas patients with COPD were more likely to be residents of nursing homes than those with LC (32% vs. 9%, respectively; p < .0001).,Higher socioeconomic status (SES) (p < .01) and patient age < 80 years (p < .001) were associated with increased access to SPC for LC patients.,Access to SPC correlated with fewer emergency room visits (p < .0001 for both COPD and LC patients) and fewer admissions to acute hospitals during the last month of life (p < .0001 for both groups).,More COPD patients died in acute hospitals than lung cancer patients, (39% vs. 20%; χ2 = 287, p < .0001), with significantly lower figures for those who had access to SPC (p < .0001).,Compared to dying COPD patients, LC patients have more access to SPC.,Access to SPC reduces the need for emergency room visits and admissions to acute hospitals. | Background: Although chronic obstructive pulmonary disease (COPD) is a life-limiting disease with a significant symptom burden, the patients are more often referred to nursing homes (NH), than to specialist palliative care (SPC) at the end of life (EOL).,This study aimed to compare patients with COPD in SPC with those in NH and to compare the care provided.,Methods: A national register study was carried out where the Swedish National Airway Register and the Swedish Register of Palliative Care were merged.,COPD patients who died in NHs or short-term facilities were included in the NH group (n = 415) and those who died in SPC were included in the SPC group (n = 355).,Demographic and clinical variables were included from the Swedish National Airway Register and variables concerning EOL care from the Swedish Register of Palliative Care.,Results: Symptom prevalence was similar in NHs and SPC, but symptom assessment (32% vs 20%), symptom relief medication (93-98% in SPC vs 74-90% in NH), EOL discussions (88% vs 66%), and bereavement support (94% vs 67%) were more likely in SPC (in all comparisons p < 0.001).,Younger age and co-habiting increased the probability of dying in SPC (p < 0.001).,Conclusion: Despite similar symptom prevalence, older persons are more likely to be referred to NHs.,If applying a palliative care philosophy in NHs, routine symptom assessment and prescription of rescue medication for frequent symptoms, would be more likely.,Promoting advance care planning and EOL discussions at an earlier stage would result in more prepared patients and families. | 1 |
Acute hyperglycemia is a common finding in patients presenting to emergency departments (EDs) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Several studies have argued against the association between hyperglycemia at admission and adverse outcomes in patients with diabetes and an acute illness.,Recent studies have shown that glucose-related variables (eg, glycemic gaps and stress hyperglycemia ratios) that are adjusted for glycated hemoglobin levels can indicate the severity of a variety of diseases.,The objective of this study was to assess whether these hemoglobin A1c (HbA1c)-based adjusted average glycemic variables were associated with unfavorable outcomes in patients admitted to a hospital with AECOPD.,We found that 1) pulmonary infection is a major risk factor for AECOPD; 2) a higher glycemic gap and modified stress hyperglycemia ratio were associated with the development of acute respiratory failure (ARF) in patients with diabetes admitted to an ED because of AECOPD; and 3) the glycemic gap and modified stress hyperglycemia ratio had superior discriminative power over acute hyperglycemia and HbA1c for predicting the development of ARF, although the HbA1c-adjusted glycemic variables alone were not independent risk factors for ARF. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally.,COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function.,We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome‐wide association study approach.,Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed.,Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE.,In COPDGene, weight loss was defined as self‐reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2).,In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits.,Stratified analyses were performed among African American (AA) and Non‐Hispanic White (NHW) participants with COPD.,Single variant and gene‐based analyses were performed adjusting for confounders.,Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation.,Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data.,At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10−8) among AA COPD participants in COPDGene.,At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively.,The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025).,The EFNA2 gene encodes the membrane‐bound protein ephrin‐A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle.,The BAIAP2 gene encodes the insulin‐responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation.,Integration of the gene‐based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling.,The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants.,Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling. | A decrease in bone mineral density (BMD) is a systemic consequence of chronic obstructive pulmonary disease (COPD).,Past reports have rarely examined any correlation between sarcopenia and BMD.,We investigated the relationship cross-sectionally between the presence of sarcopenia and BMD reduction in COPD patients.,COPD patients aged 50 or older with qualifying spirometry and dual-energy X-ray absorptiometry data were from participants in the Korean National Health and Nutrition Examination Surveys IV and V (2008-2011).,There were 286 (33.3%) subjects in the sarcopenia group and 572 (66.7%) in the non-sarcopenia group.,The sarcopenia group had lower T-scores than the non-sarcopenia group (femur: -0.73±0.88 vs. -0.18±0.97, p < 0.001; femur neck: -1.44±0.98 vs. -0.99±1.06, p < 0.001; lumbar: -1.38±1.36 vs. -0.84±1.38, p < 0.001).,The prevalences of osteopenia and osteoporosis were 60.8% and 22.0%, respectively, in the sarcopenia group and 45.6% and 13.3% in the non-sarcopenia group (both p < 0.001).,After adjusting for multiple variables, the presence of sarcopenia associated with increased the risk of osteopenia, osteoporosis, and a low BMD (OR = 3.227, 95% CI = 2.125-4.899, p < 0.001, OR = 6.952, 95% CI = 3.418-14.139, p < 0.001, and OR = 3.495, 95% CI = 2.315-5.278, p < 0.001, respectively).,In a subgroup analysis, similar OR changes were confirmed in the high-body-weight group (n = 493) (OR = 2.248, 95% CI = 1.084-4.665, p = 0.030, OR = 4.621, 95% CI = 1.167-18.291, p = 0.029, and OR = 2.376, 95% CI = 1.158-4.877, p = 0.018, respectively).,The presence of sarcopenia was associated with increased the risk for decreased BMD in COPD. | 1 |
Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations.,Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.,Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.,Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg following a run-in on their COPD therapies.,Time to ACM was prespecified.,Additional vital status data collection and subsequent analyses were performed post hoc.,Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI.,For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI.,Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient’s COPD.,Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.,This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.,Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care).,Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire.,Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items.,Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening.,Of 77 subjects, 50 participated in Phase I and 27 in Phase II.,Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity).,PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001).,Revisions were made to the draft items on the basis of cognitive interviews.,Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. | Spirometry is commonly accepted as the gold standard for the diagnosis of COPD, but the reality remains that quality assured spirometry is not or cannot be provided universally around the globe.,Adding PEF measurement to a screening questionnaire may rule out airflow limitation compatible with COPD rationalizing spirometry testing.,We conducted a cross-sectional survey in a sample of individuals 40-80 yrs. old in Dubai, UAE.,They were invited to answer a short socio-demographic questionnaire including a report on current, past history of smoking, and had PEF measured, then they conducted spirometry to identify airflow limitation compatible with COPD.,Overall, 525 (91.0%) participants performed PEF and spirometry (68% male, with a mean age of 59 years, 17% UAE Nationals), 24% reported smoking of different sorts.,Overall, 68 participants (12.9%, 95% C.I.,10.3% to 16.1%) had airflow limitation compatible with COPD.,PEFR alone identified 141participants with airflow limitation compatible with COPD, with specificity of 80% and sensitivity of 73.5%.,PEFR could be an easy, cheap, and non-biased tool to assist with the case-finding of COPD before confirmation with spirometry. | 1 |
Education on the self-management of COPD has been shown to improve patients’ quality of life and reduce hospital admissions.,This study aimed to assess the feasibility of a pilot, pragmatic COPD Chronic Care (CCC) education program led by registered respiratory therapists and determine the CCC’s impact on hospital readmissions, patient activation, and health status.,This was a prospective, randomized, pilot study of inpatients with COPD admitted to a US community hospital between August 2014 and February 2016.,In total, 308 patients were randomized 1:1 to receive standard care with or without the CCC program.,Outcomes included the number of patients completing the program, frequency and time to first all-cause and COPD-related hospital readmissions, and changes in the Patient Activation Measure (PAM) and COPD Assessment Test (CAT).,Overall, 37% (n=52) of patients in the CCC group and 29% (n=48) of patients in the control group remained in the study for 6 months and completed all follow-up phone calls.,In total, 74% (n=105) of patients in the CCC group and 69% (n=115) of patients in the control group had at least one readmission (P=0.316).,The time to first all-cause and COPD-related readmission appeared shorter for patients in the CCC group compared with the control group (mean [standard deviation]: 50.2 [54.5] vs 59.9 [63.1] days and 95.1 [80.2] vs 113.7 [82.4] days, respectively; both P=0.231).,Patients experienced significant improvement from baseline in mean PAM (both groups) and CAT (CCC group) scores.,Utilizing respiratory therapists to lead a chronic care education program for COPD in a community hospital was feasible.,Although CCC patients showed improvements in perceived symptom severity, they were readmitted sooner than control group patients.,However, the program did not impact the frequency of hospital readmissions.,A more comprehensive disease management program may be needed to improve outcomes. | COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | 1 |
To establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema.,A central electronic database was established to permit the upload of anonymised patient data from remote sites.,Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease.,Tertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities.,Data were collected from 187 patients over 1 year from eight UK academic sites.,This included patient demographics, postbronchodilator physiology, health status and CT.,Analysis was undertaken at the coordinating centre in Birmingham.,Patient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease.,CT scan suitable for analysis was available from 147 (79%) of the patients.,CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p<0.001) and carbon monoxide gas transfer (p<0.01).,Density also correlated with subjective measures of quality of life (p=0.02).,Establishment of the network for data collection and its transfer was highly successful facilitating future collaboration for the study of this rare disease and its management.,CT densitometry correlated well with the objective clinical features of the disease supporting its role as the specific marker of the associated emphysema and its severity.,Correlations with subjective measures of health, however, were generally weak indicating other factors play a role. | The clinical course of alpha-1 antitrypsin deficiency (AATD) is very heterogeneous.,It is estimated that 60% of individuals with severe AATD (Pi*ZZ) develop emphysema.,The main objective of this study was to describe the outcomes of long-term lung function in individuals with AATD-associated emphysema after at least 8 years of follow-up.,We performed a retrospective analysis of longitudinal follow-up data of AATD PiZZ patients from the Spanish registry (AATD Spanish Registry [REDAAT]).,The main follow-up outcome was the annual rate of decline in forced expiratory volume in 1 second (FEV1) calculated using the FEV1 values at baseline and in the last post-bronchodilator spirometry available.,One hundred and twenty-two AATD PiZZ patients were analyzed.,The median follow-up was 11 years (interquartile range =9-14).,The mean FEV1 decline was 28 mL/year (SD=54), with a median of 33 mL/year.,Tobacco consumption (β=19.8, p<0.001), previous pneumonia (β=27.8, p=0.026) and higher baseline FEV1% (β=0.798, p=0.016) were independently related to a faster FEV1 decline.,In this large cohort with a long follow-up, we observed a very variable decline of FEV1.,However, the mean FEV1 decline was similar to that observed in large cohorts of smoking-related COPD.,Tobacco consumption, previous pneumonia and better lung function at baseline were related to a faster decline in FEV1.,These results highlight the importance of early diagnosis and effective treatment. | 1 |
Chronic obstructive pulmonary disease (COPD) not only affects patients but also their partners.,Gender-related differences in patients with COPD are known, for instance regarding symptoms and quality of life.,Yet, research regarding gender differences in partners of patients with COPD has been conducted to a lesser extent, and most research focused on female partners.,We aimed to investigate differences between male and female partners of patients with COPD regarding their own characteristics and their perceptions of patients’ characteristics.,Cross-sectional study.,Four hospitals in the Netherlands.,One hundred and eighty-eight patient-partner couples were included in this cross-sectional study.,General and clinical characteristics, health status, care dependency, symptoms of anxiety and depression, social support, caregiver burden, and coping styles were assessed during a home visit.,Female partners had more symptoms of anxiety and a worse health status than male partners.,Social support and caregiver burden were comparable, but coping styles differed between male and female partners.,Female partners thought that male patients were less care dependent and had more symptoms of depression, while these gender differences did not exist in patients themselves.,Health care providers should pay attention to the needs of all partners of patients with COPD, but female partners in particular.,Obtaining an extensive overview of the patient-partner couple, including coping styles, health status, symptoms of anxiety, and caregiver burden, is necessary to be able to support the couple as effectively as possible. | C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial.,Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations.,A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year.,Episodes of exacerbations meeting Anthonisen’s criteria type I-II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood.,A total of 380 episodes were recorded.,Full microbiological analysis was available in 265 samples.,Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus.,Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0-28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6-79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8-93.7) (P<0.014).,H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9-167.9) and 74.1 mg/L (IQR 42.0-220.7), respectively.,In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission.,In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46-4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12-8.44) were independent predictors after adjustment for baseline characteristics.,CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated.,CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission.,Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease. | 1 |
Adherence to inhaled medications by COPD patients is a challenging issue, but relatively understudied.,The aim of this study is the characterization of adherence to inhaled medications by COPD patients, with a focus on patient-related determinants.,Stable COPD outpatients ≥40 years of age from a respiratory unit and diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria were included in a cross-sectional study.,The Measure of Treatment Adherence (MTA), the Beliefs about Medications Questionnaire (BMQ) and demographic, clinical, and COPD questionnaires were used.,After completing these questionnaires, semi-structured interviews were carried out and participants were encouraged to justify their opinions and behaviors.,Field notes were made during the interviews and each interview was analyzed before the next one.,Quantitative and qualitative analyses of the variables were then performed.,A total of 300 out of 319 participants (mean age =67.7 years, 78.1% males) completed the MTA questionnaire.,Of these, 31.3% were considered poorly adherent and 16.7% as non-adherent to the inhaled therapy.,A statistically significant negative association was found between adherence and current smoking status (P=0.044), and between adherence and FEV1% (P=0.000).,The mean BMQ Necessity score was higher in adherent patients (P=0.000), but the the mean Concern score was similar for both (P=0.877).,We found nine patterns of poor-adherence, six reasons given for poor-adherence behaviors, five reasons for good-adherence behaviors and three patient-related domains on adherence to medications.,Adherence is related to need perception and to the functional severity of the disease.,A non-adherent patient is usually a current smoker with lower degree of airflow limitation and lower perception of medication necessity.,New information obtained was related to the patterns and reasons for different adherence behaviors, which are based on three major groups of patient related-determinants: health-related experiences, health-related behaviors and health-related beliefs. | Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | 1 |
Blood eosinophil is a readily available biomarker to reflect the eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) patients, yet its association with exacerbation is inconclusive.,It is uncertain which measurement, eosinophil percentage or absolute eosinophil count, should be used and what is the optimal cutoff for exacerbation prediction.,A total of 247 COPD patients were included in this retrospective cohort study.,Blood eosinophil during stable disease state, baseline demographics, and clinical characteristics in 12 months after the index complete blood count (CBC) were recorded.,Exacerbation frequencies were compared between patients with high and low blood eosinophil percentage using 2% as cut-off.,Logistic regression and receiver operating characteristics (ROC) curve analyses were conducted.,Patients with blood eosinophil ≥2% were associated with more frequent exacerbations than patients with eosinophil <2% in the 12 months after the index CBC (mean exacerbation 1.07 vs 0.34, p < 0.001).,Higher blood eosinophil percentage conferred a higher risk of exacerbation.,Adjusted odds ratio for exacerbation in 12 months after the index CBC for blood eosinophil ≥2% was 2.98 (95% confidence interval = 1.42-6.25).,The area under the ROC curve of eosinophil percentage was significantly higher than that of absolute eosinophil count (0.678 vs 0.640, p = 0.010).,The optimal cutoff of blood eosinophil percentage for exacerbation prediction was 2.8%.,Blood eosinophilia was associated with higher exacerbation risk in COPD patients.,Further studies are required to elucidate the mechanism of eosinophilic inflammation in COPD and determine the optimal treatment strategy to reduce exacerbations. | Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation.,Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes.,Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.,This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies.,Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study.,Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.,Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150-300 cells/μL and 20.1% with > 300 cells/μL.,The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count.,When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150-300 cells/μL and 0.44 for > 300 cells/μL respectively).,A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively.,For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150-300 cells/μL) and 1.07 (> 300 cells/μL).,Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).,We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate.,Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.,ClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195. | 1 |
In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear.,Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen.,We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD.,Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality.,A nested subcohort of 141 patients, followed for up to 6 months, was studied to test if MBL deficiency was associated with altered sputum microbiota, through 16S rRNA PCR and sequencing, or airway inflammation during stable and exacerbated COPD.,Patients with MBL deficiency with COPD were significantly less likely to have severe exacerbations (incidence rate ratio (IRR) 0.66, 95% CI 0.48 to 0.90, p=0.009), or to have moderate or severe exacerbations (IRR 0.77, 95% CI 0.60 to 0.99, p=0.047).,MBL deficiency did not affect rate of FEV1 decline or mortality.,In the subcohort, patients with MBL deficiency had a more diverse lung microbiota (p=0.008), and were less likely to be colonised with Haemophilus spp.,There were lower levels of airway inflammation in patients with MBL deficiency.,Patients with MBL deficient genotype with COPD have a lower risk of exacerbations and a more diverse lung microbiota.,This is the first study to identify a genetic association with the lung microbiota in COPD. | Viral-bacterial co-infections are associated with severe exacerbations of COPD.,Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses.,In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients.,When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (p<0.05).,The combination of virus and flagellin replicated this synergistic increase (p<0.05), and synergy was not seen using a flagella-deficient mutant Pseudomonas (p<0.05).,The effects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5.,The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5.,Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection.,Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (p<0.05).,We conclude that co-exposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients.,This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections. | 1 |
Supplemental Digital Content is available in the text,Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality.,This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival.,Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry.,Cases with lung adenocarcinoma were followed until the end of 2010.,Survival curves were estimated by the Kaplan-Meier method.,Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma.,A total of 14,518 cases were identified with lung adenocarcinoma.,Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10-2.58), 1.48 (95% CI, 1.14-1.93), and 1.27 (95% CI, 1.08-1.49) for individuals with stage I + II, III, and IV diseases, respectively.,The HRs for asthma were 1.41 (95% CI, 1.00-1.99) in women with stage I + II and 1.14 (95% CI, 1.04-1.26) in men with stage IV disease.,For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12-1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12-1.63) for COPD + TB, 1.28 (95% CI, 1.01-1.63) for TB, and 1.15 (95%CI, 1.04-1.27) for asthma + COPD, respectively.,For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72-17.71) for asthma + COPD + TB.,Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma.,TB is at elevated risk of mortality among men with different stages of adenocarcinoma.,Asthmatic women with early-stage adenocarcinoma had increased risk of mortality. | Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking.,Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress.,Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.,There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients.,Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema.,Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung.,Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.,In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed.,The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema. | 1 |
Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD) medications are already known to be suboptimal.,Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications), may have an adverse impact on adherence to mCOPD medications.,The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients.,COPD patients were identified using a large administrative claims database.,Selected patients were 40-89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date) during January 1, 2009 to December 31, 2010.,Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription.,Adherence (proportion of days covered [PDC]) was measured during 365 days following the first COPD prescription.,The association between non-adherence (PDC <0.8) to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics.,A total of 14,117 patients, with a mean age of 69.9 years, met study criteria.,Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47.,Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38-1.78, all P<0.01).,Adherence to mCOPD medications is low.,Non-adherence (or adherence) to mCOPD medications is positively related to non-adherence (or adherence) to non-COPD medications, implying that the need to take medications prescribed for comorbid conditions does not adversely impact adherence to mCOPD medications. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide.,Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age.,Spirometry is the method used for diagnosing COPD.,However, identifying patients at risk of COPD to undergo spirometry tests has been challenging.,Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers.,Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease.,Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection.,Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria.,Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD.,The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 ≥ 80% of predicted), 53% in stage 2 (50 ≤ FEV1 < 80% of predicted), 3% in stage 3 (30 ≤ FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted).,We found a significant association between COPD and age ≥ 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]).,Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD.,A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD.,These patients should be offered spirometry testing for diagnosis of COPD. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential. | 1 |
This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks.,The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over weeks 12-24.,Secondary endpoints included symptoms, health-related quality of life, and safety.,Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint.,In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference − 4 mL; P = 0.8316).,BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints.,BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI.,All treatments were well tolerated.,Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β2-agonist), as well as symptoms and exacerbations relative to dual therapies.,Findings support BGF MDI use in Chinese patients with moderate to very severe COPD.,ClinicalTrials.gov NCT02497001.,The online version of this article (10.1007/s12325-020-01266-5) contains supplementary material, which is available to authorized users. | With increasing choice of medications and devices for asthma and chronic obstructive pulmonary disease (COPD) treatment, comparative evidence may inform treatment decisions.,This systematic literature review assessed clinical and economic evidence for using a single combination inhaler versus multiple inhalers to deliver the same medication for patients with asthma or COPD.,In 2016, Embase, PubMed and the Cochrane library were searched for publications reporting studies in asthma or COPD comparing a single-inhaler combination medicine with multiple inhalers delivering the same medication.,Publications included English-language articles published since 1996 and congress abstracts since 2013.,Clinical, economic and adherence endpoints were assessed.,Of 2031 abstracts screened, 18 randomized controlled trials (RCTs) in asthma and four in COPD, nine retrospective and three prospective observational studies in asthma, and four observational studies in COPD were identified.,Of these, five retrospective and one prospective study in asthma, and two retrospective studies in COPD reported greater adherence with a single inhaler than multiple inhalers.,Nine observational studies reported significantly (n=7) or numerically (n=2) higher rates of adherence with single- versus multiple-inhaler therapy.,Economic analyses from retrospective and prospective studies showed that use of single-inhaler therapies was associated with reduced healthcare resource use (n=6) and was cost-effective (n=5) compared with multiple-inhaler therapies.,Findings in 18 asthma RCTs and one prospective study reporting lung function, and six RCTs reporting exacerbation rates, showed no significant differences between a single inhaler and multiple inhalers.,This was in contrast to several observational studies reporting reductions in healthcare resource use or exacerbation events with single-inhaler treatment, compared with multiple inhalers.,Retrospective and prospective studies showed that single-inhaler use was associated with decreased healthcare resource utilization and improved cost-effectiveness compared with multiple inhalers.,Lung function and exacerbation rates were mostly comparable in the RCTs, possibly due to study design. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is an increasingly recognized phenotype.,Few randomized clinical trials have been conducted in patients with ACOS; therefore, scientific evidence concerning ACOS is scarce and a therapeutic approach remains unclear.,The aim of this study was to evaluate current treatment trends for patients with ACOS, identified as those with a dual definition of asthma and COPD, in a real-world COPD cohort.,Data were analyzed from patients with asthma and COPD in the USA, France, Germany, Italy, Spain, and the UK who participated in the 2012 and 2013 Adelphi Respiratory Disease Specific Programmes (DSPs).,Patients with ACOS were identified in the COPD population; these patients had a physician-confirmed, concomitant asthma diagnosis.,Physicians completed a patient record form providing information on patient and disease characteristics including prescribed respiratory treatment.,Pairwise comparisons were made between the ACOS, asthma, and COPD populations using χ2 tests.,In total, 9,042 patients with asthma-only, 7,119 patients with COPD-only, and 523 patients with ACOS (a dual diagnosis of asthma and COPD) participated in the study.,The most commonly prescribed regimens were inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) + long-acting muscarinic antagonist (LAMA); (ACOS 30%, asthma 1.4%, and COPD 32%), ICS/LABA (19%, 41.5%, and 17%, respectively), and LAMA (6%, 0.4%, and 19%, respectively); 18% of patients with ACOS were not prescribed an ICS.,Patients with ACOS had a significantly higher incidence of gastroesophageal reflux disease, diabetes, and obesity and experienced more exacerbations in the past year than those with COPD or asthma.,The majority of patients with ACOS, as defined in this research, were prescribed similar treatment to those with COPD.,There is a need, however, for better treatment for patients with ACOS, as indicated by symptoms and exacerbation levels.,A clearer therapeutic approach for patients with ACOS is required. | Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | 1 |
IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.,Subgroup analyses assessed whether the efficacy of FF/UMEC/VI versus FF/VI or UMEC/VI and UMEC/VI versus FF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts.,Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)).,End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).,Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI group versus FF/VI (single moderate 20% (10-29), frequent moderate 11% (2-19), severe 17% (7-26)) and versus UMEC/VI (single moderate 18% (5-29), frequent moderate 29% (21-37), severe 26% (14-35)).,Moderate/severe exacerbation rates were reduced in the FF/VI group versus UMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (−12-18), frequent moderate 21% (11-29), severe 11% (−3-22)).,Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts.,FF/UMEC/VI improved lung function and health status versus both dual therapies irrespective of exacerbation subgroup.,UMEC/VI improved lung function versus FF/VI in all subgroups.,Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population.,Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.,FF/UMEC/VI shows benefits vs FF/VI and UMEC/VI across multiple endpoints irrespective of exacerbation history.,Exacerbation history and eosinophils influenced the comparison between UMEC/VI and FF/VI, and eosinophils that between FF/UMEC/VI and UMEC/VI.http://bit.ly/2SHu2ey | Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | 1 |
Measurements of eosinophils in induced sputum and fractional exhaled nitric oxide (FeNO) are noninvasive biomarkers for assessing airway inflammation phenotypes in chronic obstructive pulmonary disease (COPD).,Nevertheless, the clinical application of the correlation between FeNO levels and sputum eosinophilia is controversial.,The study aimed to investigate the correlation and predictive relationship between FeNO levels and sputum eosinophils in patients with COPD exacerbation.,It also examined the relationship between FeNO levels and blood eosinophil percentage.,A total of 163 patients with COPD exacerbation were included in the cross-sectional study.,All patients underwent the following on the same day: FeNO test, spirometry, bronchodilator reversibility test, induced sputum, and routine blood test.,They were classified as eosinophilic group or noneosinophilic group based on sputum eosinophilic percentage (≥2.5%)/FeNO levels (≥32 parts per billion [ppb]).,FeNO levels and blood eosinophilic percentage were higher in patients with sputum eosinophilia (n=62) compared to those without (31.35 ppb versus 21.43 ppb, P=0.015; 2.71% versus 0.98%, P<0.0001, respectively).,Sputum eosinophilic percentage was higher with raised FeNO (n=34) compared to those with FeNO <32 ppb (5.12% versus 3.12%, P=0.007).,Eosinophils in induced sputum correlated with both FeNO levels (ρ=0.221, P=0.005) and blood eosinophilic percentage (ρ=0.399, P<0.001).,There was no relationship between FeNO and blood eosinophilic percentage.,Blood eosinophilic percentage was predictive of sputum eosinophilia (95% confidence interval [CI] =0.65-0.81, P<0.001) at a cutoff point of 0.65% (sensitivity =73%, specificity =61.3%).,FeNO levels were predictive of sputum eosinophilia (95% CI =0.53-3,071, P=0.012) at a cutoff point of 17.5 ppb (sensitivity =65.1%, specificity =56.4%).,The clinical relevance of this study provides evidence that inflammatory biomarkers, including sputum eosinophilic percentage, FeNO level, and blood eosinophilic percentage, can be used to positively diagnose eosinophilic COPD.,The FeNO level and blood eosinophilic counts/percentage, which determine an optimal cutoff for sputum eosinophilia, need more studies. | COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality.,Only 10%-25% of COPD exacerbations are eosinophilic.,To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU.,This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014.,Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included.,Data were collected electronically from the hospital database.,Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded.,COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic).,These groups were compared with the recorded data.,Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2).,Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU.,Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2-7 days) vs 6 days (3-9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively.,COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%.,NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management. | 1 |
Telemonitoring of symptoms and physiological signs has been suggested as a means of early detection of chronic obstructive pulmonary disease (COPD) exacerbations, with a view to instituting timely treatment.,However, algorithms to identify exacerbations result in frequent false-positive results and increased workload.,Machine learning, when applied to predictive modelling, can determine patterns of risk factors useful for improving prediction quality.,Our objectives were to (1) establish whether machine learning techniques applied to telemonitoring datasets improve prediction of hospital admissions and decisions to start corticosteroids, and (2) determine whether the addition of weather data further improves such predictions.,We used daily symptoms, physiological measures, and medication data, with baseline demography, COPD severity, quality of life, and hospital admissions from a pilot and large randomized controlled trial of telemonitoring in COPD.,We linked weather data from the United Kingdom meteorological service.,We used feature selection and extraction techniques for time series to construct up to 153 predictive patterns (features) from symptom, medication, and physiological measurements.,We used the resulting variables to construct predictive models fitted to training sets of patients and compared them with common symptom-counting algorithms.,We had a mean 363 days of telemonitoring data from 135 patients.,The two most practical traditional score-counting algorithms, restricted to cases with complete data, resulted in area under the receiver operating characteristic curve (AUC) estimates of 0.60 (95% CI 0.51-0.69) and 0.58 (95% CI 0.50-0.67) for predicting admissions based on a single day’s readings.,However, in a real-world scenario allowing for missing data, with greater numbers of patient daily data and hospitalizations (N=57,150, N+=55, respectively), the performance of all the traditional algorithms fell, including those based on 2 days’ data.,One of the most frequently used algorithms performed no better than chance.,All considered machine learning models demonstrated significant improvements; the best machine learning algorithm based on 57,150 episodes resulted in an aggregated AUC of 0.74 (95% CI 0.67-0.80).,Adding weather data measurements did not improve the predictive performance of the best model (AUC 0.74, 95% CI 0.69-0.79).,To achieve an 80% true-positive rate (sensitivity), the traditional algorithms were associated with an 80% false-positive rate: our algorithm halved this rate to approximately 40% (specificity approximately 60%).,The machine learning algorithm was moderately superior to the best symptom-counting algorithm (AUC 0.77, 95% CI 0.74-0.79 vs AUC 0.66, 95% CI 0.63-0.68) at predicting the need for corticosteroids.,Early detection and management of COPD remains an important goal given its huge personal and economic costs.,Machine learning approaches, which can be tailored to an individual’s baseline profile and can learn from experience of the individual patient, are superior to existing predictive algorithms and show promise in achieving this goal.,International Standard Randomized Controlled Trial Number ISRCTN96634935; http://www.isrctn.com/ISRCTN96634935 (Archived by WebCite at http://www.webcitation.org/722YkuhAz) | Recent telehealth studies have demonstrated minor impact on patients affected by long-term conditions.,The use of technology does not guarantee the compliance required for sustained collection of high-quality symptom and physiological data.,Remote monitoring alone is not sufficient for successful disease management.,A patient-centred design approach is needed in order to allow the personalisation of interventions and encourage the completion of daily self-management tasks.,A digital health system was designed to support patients suffering from chronic obstructive pulmonary disease in self-managing their condition.,The system includes a mobile application running on a consumer tablet personal computer and a secure backend server accessible to the health professionals in charge of patient management.,The patient daily routine included the completion of an adaptive, electronic symptom diary on the tablet, and the measurement of oxygen saturation via a wireless pulse oximeter.,The design of the system was based on a patient-centred design approach, informed by patient workshops.,One hundred and ten patients in the intervention arm of a randomised controlled trial were subsequently given the tablet computer and pulse oximeter for a 12-month period.,Patients were encouraged, but not mandated, to use the digital health system daily.,The average used was 6.0 times a week by all those who participated in the full trial.,Three months after enrolment, patients were able to complete their symptom diary and oxygen saturation measurement in less than 1 m 40s (96% of symptom diaries).,Custom algorithms, based on the self-monitoring data collected during the first 50 days of use, were developed to personalise alert thresholds.,Strategies and tools aimed at refining a digital health intervention require iterative use to enable convergence on an optimal, usable design.,‘Continuous improvement’ allowed feedback from users to have an immediate impact on the design of the system (e.g., collection of quality data), resulting in high compliance with self-monitoring over a prolonged period of time (12-month).,Health professionals were prompted by prioritisation algorithms to review patient data, which led to their regular use of the remote monitoring website throughout the trial.,Trial registration: ISRCTN40367841.,Registered 17/10/2012. | 1 |
Tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), a debilitating respiratory condition with high mortality and morbidity (1,2).,However, an estimated 24% of adults with COPD have never smoked (3,4).,Among these persons, 26%-53% of COPD can be attributed to workplace exposures, including dust, fumes, gases, vapors, and secondhand smoke exposure (4-6).,To assess industry-specific and occupation-specific COPD prevalence among adults aged ≥18 years who have never smoked and who were employed any time during the past 12 months, CDC analyzed 2013-2017 National Health Interview Survey (NHIS) data.,Among an estimated 106 million workers who had never smoked, 2.2% (2.4 million) have COPD.,Highest prevalences were among workers aged ≥65 years (4.6%), women (3.0%), and those reporting fair/poor health (6.7%).,Among industries and occupations, the highest COPD prevalences were among workers in the information industry (3.3%) and office and administrative support occupations (3.3%).,Among women, the highest prevalences were among those employed in the information industry (5.1%) and in the transportation and material moving occupation (4.5%), and among men, among those employed in the agriculture, forestry, fishing, and hunting industry (2.3%) and the administrative and support, waste management, and remediation services industry (2.3%).,High COPD prevalences in certain industries and occupations among persons who have never smoked underscore the importance of continued surveillance, early identification of COPD, and reduction or elimination of COPD-associated risk factors, such as the reduction of workplace exposures to dust, vapors, fumes, chemicals, and exposure to indoor and outdoor air pollutants. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030.,Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles.,In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice.,Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway.,The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses.,A second objective was to validate the model in relation to existing epidemiology studies of COPD.,A patient simulation model was developed in Microsoft Excel™.,The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data.,Each patient moves through the model with demographic characteristics randomly generated from a set distribution.,These characteristics determine the risk of clinical events occurring in the model.,The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity.,The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways.,The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies.,It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses. | To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes. | 1 |
Pulmonary rehabilitation (PR) reduces the number and duration of hospital admissions and readmissions, and improves health-related quality of life in patients with COPD.,Despite clinical guideline recommendations, under-referral and limited uptake to PR contribute to poor treatment access.,We reviewed published literature on the effectiveness of interventions to improve referral to and uptake of PR in patients with COPD when compared to standard care, alternative interventions, or no intervention.,The review followed recognized methods.,Search terms included “pulmonary rehabilitation” AND “referral” OR “uptake” applied to MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, BNI, Web of Science, and Cochrane Library up to January 2018.,Titles, abstracts, and full papers were reviewed independently and quality appraised.,The protocol was registered (PROSPERO # 2016:CRD42016043762).,We screened 5,328 references.,Fourteen papers met the inclusion criteria.,Ten assessed referral and five assessed uptake (46,146 patients, 409 clinicians, 82 hospital departments, 122 general practices).,One was a systematic review which assessed uptake.,Designs, interventions, and scope of studies were diverse, often part of multifaceted evidence-based management of COPD.,Examples included computer-based prompts at practice nurse review, patient information, clinician education, and financial incentives.,Four studies reported statistically significant improvements in referral (range 3.5%-36%).,Two studies reported statistically significant increases in uptake (range 18%-21.5%).,Most studies had methodological and reporting limitations.,Meta-analysis was not conducted due to heterogeneity of study designs.,This review demonstrates the range of approaches aimed at increasing referral and uptake to PR but identifies limited evidence of effectiveness due to the heterogeneity and limitations of study designs.,Research using robust methods with clear descriptions of intervention, setting, and target population is required to optimize access to PR across a range of settings. | With the limited reach of pulmonary rehabilitation (PR) and low levels of daily physical activity in chronic obstructive pulmonary disease (COPD), a need exists to increase daily exercise.,This study evaluated telephone health-mentoring targeting home-based walking (tele-rehab) compared to usual waiting time (usual care) followed by group PR.,People with COPD were randomized to tele-rehab (intervention) or usual care (controls).,Tele-rehab delivered by trained nurse health-mentors supported participants’ home-based walking over 8-12 weeks.,PR, delivered to both groups simultaneously, included 8 weeks of once-weekly education and self-management skills, with separate supervised exercise.,Data were collected at three time-points: baseline (TP1), before (TP2), and after (TP3) PR.,The primary outcome was change in physical capacity measured by 6-minute walk distance (6MWD) with two tests performed at each time-point.,Secondary outcomes included changes in self-reported home-based walking, health-related quality of life, and health behaviors.,Of 65 recruits, 25 withdrew before completing PR.,Forty attended a median of 6 (4) education sessions.,Seventeen attended supervised exercise (5±2 sessions).,Between TP1 and TP2, there was a statistically significant increase in the median 6MWD of 12 (39.1) m in controls, but no change in the tele-rehab group.,There were no significant changes in 6MWD between other time-points or groups, or significant change in any secondary outcomes.,Participants attending supervised exercise showed a nonsignificant improvement in 6MWD, 12.3 (71) m, while others showed no change, 0 (33) m.,The mean 6MWD was significantly greater, but not clinically meaningful, for the second test compared to the first at all time-points.,Telephone-mentoring for home-based walking demonstrated no benefit to exercise capacity.,Two 6-minute walking tests at each time-point may not be necessary.,Supervised exercise seems essential in PR.,The challenge of incorporating exercise into daily life in COPD is substantial. | 1 |
Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood.,Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD).,The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood.,We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort.,Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13.,The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = −0.068 g/L per minor allele (P = 1.20*10−12).,But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants.,Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57).,Extending the analysis to lung function revealed a more complex situation.,Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants.,Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population. | The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation.,Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation.,With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD).,In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method.,We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method.,In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography.,Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE.,sRAGE was significantly lower (p = 0.007) in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL) than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL), and was correlated with the severity of emphysema (p < 0.001), the lower the level of sRAGE the greater the degree of emphysema on CT.,The relationship remained statistically significant after adjusting for smoking history and comorbid conditions.,In addition, sRAGE was significantly lower in COPD patients with chronic cor pulmonale than in those without (p = 0.002).,Such difference remained statistically significant after adjusting for smoking history, comorbidities, and emphysema severity.,There was no significant difference in the plasma levels of the two RAGE ligands between cases and controls.,sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction.,Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD. | 1 |
Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain.,This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.,Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects.,In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.,Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort.,Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects.,In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups.,Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.,MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression.,Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. | Alveolar apoptosis is increased in the emphysematous lung.,However, mechanisms involved are not fully understood.,Recently, we demonstrated that levels of TRAIL receptor 1 and 2, levels of p53, and Bax/Bcl-xL ratio were elevated in the lung of subjects with emphysema, despite smoking cessation.,Thus, we postulate that due to chronic pulmonary oxidative stress, the emphysematous lung would be abnormally sensitive to TRAIL-mediated apoptosis.,A549 cells were exposed to rTRAIL, cigarette smoke extract, and/or H2O2 prior to caspase-3 activity measurement and annexin V staining assessment.,In addition, freshly resected lung samples were obtained from non-emphysematous and emphysematous subjects and exposed ex vivo to rTRAIL for up to 18 hours.,Lung samples were harvested and levels of active caspase-3 and caspase-8 were measured from tissue lysates.,Both cigarette smoke extract and H2O2 were able to sensitize A549 cells to TRAIL-mediated apoptosis.,Moreover, following exposure to rTRAIL, caspase-3 and -8 were activated in lung explants from emphysematous subjects while being decreased in lung explants from non-emphysematous subjects.,Alveolar sensitivity to TRAIL-mediated apoptosis is strongly increased in the emphysematous lung due to the presence of oxidative stress.,This might be a new mechanism leading to increased alveolar apoptosis and persistent alveolar destruction following smoking cessation. | 1 |
Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer. | Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease.,Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD.,However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD.,miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR.,Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry.,Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR.,Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1.,We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01).,We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure.,Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects.,Subsequent investigation found that CCN1 was a direct target of miR-181c.,CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01).,Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment. | 1 |
Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most.,This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most.,Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search.,Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models.,Fourteen trials representing 3,282 patients were included.,Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality.,Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026).,In none of these subgroups, a consistent effect was shown on all relevant outcomes.,Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice.,Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended. | To examine whether lack of measurement invariance (MI) influences mean comparisons among different disease groups, this paper provides (1) a systematic review of MI in generic constructs across chronic conditions and (2) an empirical analysis of MI in the Health Education Impact Questionnaire (heiQ™).,(1) We searched for studies of MI among different chronic conditions in online databases.,(2) Multigroup confirmatory factor analyses were used to study MI among five chronic conditions (orthopedic condition, rheumatism, asthma, COPD, cancer) in the heiQ™ with N = 1404 rehabilitation inpatients.,Impact on latent and composite mean differences was examined.,(1) A total of 30 relevant studies suggested that about one in three items lacked MI.,However, only four studies examined impact on latent mean differences.,Scale means were only affected in one of these three studies.,(2) Across the eight heiQ™ scales, seven scales had items with lack of MI in at least one disease group.,However, in only two heiQ™ scales were some latent or composite mean differences affected.,Lack of MI among disease groups is common and may have a relevant influence on mean comparisons when using generic instruments.,Therefore, when comparing disease groups, tests of MI should be implemented.,More studies of MI and according impact on mean differences in generic questionnaires are needed. | 1 |
Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD).,In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days’ administration of doses up to 700 μg.,In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days.,A total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV1] 44% of predicted) were randomized in a double-blind, placebo-controlled parallel group study.,Inhaled corticosteroids as well as short-acting bronchodilators were permitted.,Once-daily treatments (44, 88, 175 or 350 μg revefenacin or matching placebo) were administered by a standard jet nebulizer, for 28 days.,The primary endpoint was change from baseline in D28 trough FEV1, and secondary endpoints included weighted mean FEV1 over 0 to 24 h and rescue medication (albuterol) use.,Safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles.,Revefenacin (88, 175 and 350 μg) significantly improved D28 trough FEV1 over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 μg produced a sub-therapeutic response.,At doses ≥88 μg, more than 80% of patients achieved at least a 100-mL increase from baseline FEV1 in the first 4 h post dose compared with 33% of placebo patients.,For doses ≥88 μg, D28 24 h weighted mean differences from placebo for FEV1 were numerically similar to respective trough FEV1 values, indicating bronchodilation was sustained for 24 h post dose.,Doses ≥88 μg reduced the average number of albuterol puffs/day by more than one puff/day.,The 350 μg dose did not demonstrate additional efficacy over that observed with 175 μg revefenacin.,Revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects.,These data suggest that 88 and 175 μg revefenacin are appropriate doses for use in longer-term safety and efficacy trials.,Revefenacin offers the potential for the first once-daily LAMA for nebulization in patients with COPD who require or prefer a nebulized drug delivery option.,ClinicalTrials.gov NCT02040792.,Registered January 16, 2014. | 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 |
Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality.,Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD.,The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.,This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE.,Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls.,Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.,A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included.,The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016-2,319) compared to 781 ng/mL (IQR 523-855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209-636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=−0.35), P=0.01 for both comparisons.,In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA.,Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93-3.95, P=0.08).,Plasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study. | Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD. | 1 |
The diagnosis of chronic obstructive pulmonary disease (COPD) is usually made based on history and physical exam alone.,Symptoms of dyspnea, cough, and wheeze are nonspecific and attributable to a variety of diseases.,Confirmatory testing to verify the airflow obstruction is available but rarely used, which may result in substantial misdiagnoses of COPD.,The aim of this study is to evaluate the use of confirmatory testing and assess the accuracy of the diagnosis.,From January 2011 through December 2013, 6,018 patients with COPD as a principal or leading diagnosis were admitted at a community teaching hospital.,Of those, only 504 (8.4%) patients had spirometry performed during hospitalization.,The studies were reviewed by two board-certified pulmonologists to verify presence of persistent airflow obstruction.,Charts of these patients were then examined to determine if the spirometry results had changed the diagnosis or the treatment plan for these patients.,Spirometry confirmed the diagnosis of COPD in 270 patients (69.2%) treated as COPD during their hospitalization.,Restrictive lung disease was found to be present in 104 patients (26.6%) and normal in 16 patients (4.2%).,Factors predictive of airflow obstruction included smoking status and higher pack-year history.,Negative predictive factors included higher body mass index (BMI) and other medical comorbidities.,These patients were significantly more likely to be misdiagnosed and mistreated as COPD.,Up to a third of patients diagnosed and treated as COPD in the hospital may be inaccurately diagnosed as COPD based on confirmatory spirometry testing.,Factors contributing to the inaccuracy of diagnosis include less smoking history, high BMI, and associated comorbidities. | COPD exacerbations have a negative impact on lung function, decrease quality of life (QoL) and increase the risk of death.,The objective of this study was to assess the course of health status after an outpatient or inpatient exacerbation in patients with COPD.,This is an epidemiological, prospective, multicentre study that was conducted in 79 hospitals and primary care centres in Spain.,Four hundred seventy-six COPD patients completed COPD assessment test (CAT) and Clinical COPD Questionnaire (CCQ) questionnaires during the 24 hours after presenting at hospital or primary care centres with symptoms of an exacerbation, and also at weeks 4-6.,The scores from the CAT and CCQ were evaluated and compared at baseline and after recovery from the exacerbation.,A total of 164 outpatients (33.7%) and 322 inpatients (66.3%) were included in the study.,The majority were men (88.2%), the mean age was 69.4 years (SD = 9.5) and the mean FEV1 (%) was 47.7% (17.4%).,During the exacerbation, patients presented high scores in the CAT: [mean: 22.0 (SD = 7.0)] and the CCQ: [mean: 4.4 (SD = 1.2)].,After recovery there was a significant reduction in the scores of both questionnaires [CAT: mean: -9.9 (SD = 5.1) and CCQ: mean: -3.1 (SD = 1.1)].,Both questionnaires showed a strong correlation during and after the exacerbation and the best predictor of the magnitude of improvement in the scores was the severity of each score at onset.,Due to their good correlation, CAT and CCQ can be useful tools to measure health status during an exacerbation and to evaluate recovery.,However, new studies are necessary in order to identify which factors are influencing the course of the recovery of health status after a COPD exacerbation. | 1 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es | 1 |
To determine the prevalence of COPD in Taiwan and to document the disease characteristics and associated risk factors.,We conducted a random cross-sectional national survey of adults older than 40 years in Taiwan.,Respiratory health screening questions identified subjects with diagnosed COPD or whose reported symptoms also fulfilled an epidemiological case definition; these were eligible to complete the survey, which also included indices of symptom severity and disability and questions on comorbidities, medical treatments, smoking habits, and occupations potentially harmful to respiratory health.,Subjects with diagnosed COPD were subdivided by smoking status.,Subjects who fulfilled the case definition of COPD and smoked were designated as “possible COPD”.,Participants who did not fit the case definition of COPD were asked only about their personal circumstances and smoking habits.,Data from these groups were analyzed and compared.,Of the 6,600 participants who completed the survey, 404 (6.1%) fulfilled the epidemiological case definition of COPD: 137 with diagnosed COPD and 267 possible COPD.,The most common comorbidities of COPD were hypertension or cardiovascular diseases (36.1%).,Subjects with definite COPD had significantly higher COPD Assessment Test scores than the possible COPD group (14.6±8.32 vs 12.6±6.49, P=0.01) and significantly more comorbid illnesses (P=0.01).,The main risk factors contributing to health care utilization in each COPD cohort were higher COPD Assessment Test scores (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.26), higher modified Medical Research Council Breathlessness Scale scores (OR 1.97, 95% CI 1.11-3.51), and having more than one comorbidity (OR 5.19, 95% CI 1.05-25.61).,With estimated prevalence of 6.1% in the general population, COPD in Taiwan has been underdiagnosed.,Symptoms and comorbidities were independent risk factors for health care utilization in subjects with definite or possible COPD.,There is an urgent need to raise awareness of the importance of early evaluation and prompt treatment for subjects with chronic airway symptoms. | Patients with chronic obstructive pulmonary disease (COPD) have increased mortality following myocardial infarction (MI) compared with patients without COPD.,We investigated the extent to which differences in recognition and management after MI could explain the mortality difference.,300 161 patients with a first MI between 2003 and 2013 were identified in the UK Myocardial Ischaemia National Audit Project database.,Logistic regression was used to compare mortality in hospital and at 180 days postdischarge between patients with and without COPD.,Variables relating to inhospital factors (delay in diagnosis, use of reperfusion and time to reperfusion/use of angiography) and use of secondary prevention were sequentially added to models.,Mortality was higher for patients with COPD both inhospital (4.6% vs 3.2%) and at 180 days (12.8% vs 7.7%).,After adjusting for inhospital factors, the effect of COPD on inhospital mortality after MI was reduced for both ST-elevation myocardial infarctions (STEMIs) and non-STEMIs (STEMIs OR 1.24 (95% CI 1.10 to 1.41) to 1.13 (95% CI 0.99 to 1.29); non-STEMIs OR 1.34 (95% CI 1.24 to 1.45) to 1.16 (95% CI 1.07 to 1.26)).,Adjusting for inhospital factors reduced the effect of COPD on mortality after non-STEMI at 180 days (OR 1.56 (95% CI 1.47 to 1.65) to 1.37 (95% CI 1.31 to 1.44)).,Adjusting for use of secondary prevention also reduced the effect of COPD on mortality at 180 days for STEMIs and non-STEMIs (STEMIs OR 1.45 (95% CI 1.31 to 1.61) to 1.25 (95% CI 1.11 to 1.41); non-STEMIs OR 1.37 (95% CI 1.31 to 1.44) to 1.26 (95% CI 1.17 to 1.35).,Delayed diagnosis, timing and use of reperfusion of a STEMI, use of angiography after a non-STEMI and use of secondary prevention medicines are all potential explanations for the mortality gap after MI in people with COPD. | 1 |
The purpose of this study was to compare matrix metalloproteinase-12 (MMP-12), neutrophil elastase (NE), and tissue inhibitor of metalloproteinase-4 (TIMP-4) in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and controls.,At the same time, MMP-12, NE, and TIMP-4 in exhaled breath condensate (EBC) were also evaluated.,Peripheral blood and EBC samples from COPD patients and healthy controls were collected.,In serum and EBC, MMP-12, NE, and TIMP-4 proteins were detected by enzyme-linked immunoassays.,The mRNA expression levels of MMP-12, NE, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR).,The concentration of TIMP-4 protein in EBC was lower in patients with COPD (P < 0.001).,MMP-12 (P = 0.046), NE (P = 0.027), and TIMP-4 (P = 0.005) proteins in serum of patients with COPD showed higher levels of concentration.,The mRNA of MMP-12 (P = 0.0067), NE (P = 0.0058), and TIMP-4 (P = 0.0006) in PBMCs of COPD patients showed higher expression levels.,Compared with stable patients, mRNA expression level of NE (P = 0.033) in PBMCs of patients with acute exacerbation of COPD was increased.,There were differences in the ratio of MMP-12/TIMP-4 in PBMC (P = 0.0055), serum (P = 0.0427), and EBC (P = 0.0035) samples between COPD patients and healthy controls.,The mRNA expression of MMP-12 (r = −0.3958, P = 0.0186) and NE (r = −0.3694, P = 0.0290) in COPD patients was negatively correlated with pulmonary function.,However, the mRNA expression of TIMP-4 (r = 0.2871, P = 0.0945) in PBMCs was not correlated with the FEV1 of the pulmonary function.,Serum MMP-12 level was positively correlated with the MMP-12 level in EBC (P = 0.0387).,The level of TIMP-4 in serum was not correlated with the level in the EBC sample (P = 0.4332).,The expression levels of MMP-12, NE, and TIMP-4 in PBMCs and serum were elevated in COPD patients.,In PBMCs of COPD patients, the mRNA expression level of NE may predict acute exacerbation, and MMP-12 mRNA expression level may be used to reflect the severity of airflow limitation.,However, to better assess their diagnostic or prognostic value, larger studies are necessary. | Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD. | 1 |
Some COPD patients are more susceptible to exacerbations than others.,Mechanisms underlying these differences in susceptibility are not well understood.,We hypothesized that altered cell mediated immune responses may underlie a propensity to suffer from frequent exacerbations in COPD.,Peripheral blood mononuclear cells (PBMCs) were obtained from 24 stable COPD patients, eight frequent exacerbators (≥3 diary-card exacerbations/year) and 16 infrequent exacerbators (< 3 diary-card exacerbations/year).,Detailed multi-parameter flow cytometry was used to study differences in innate and adaptive systemic immune function between frequent and infrequently exacerbating COPD patients.,The 24 COPD patients had a mean (SD) age of 76.3 (9.4) years and FEV1 1.43 (0.60)L, 53.3 (18.3)% predicted.,PBMCs of frequent exacerbators (FE) contained lower frequencies of CD4+ T central memory cells (CD4+ Tcm) compared to infrequent exacerbators (IE) (FE = 18.7 %; IE = 23.9 %; p = 0.035).,This observation was also apparent in absolute numbers of CD4+ Tcm cells (FE = 0.17 × 10^6/mL; IE = 0.25 × 10^6/mL; p = 0.035).,PBMCs of FE contained a lower frequency of CD8+ T effector memory cells expressing HLA-DR (Human Leukocyte Antigen - D Related) compared to IE COPD patients (FE = 22.7 %; IE = 31.5 %; p = 0.007).,Differences in the adaptive systemic immune system might associate with exacerbation susceptibility in the ‘frequent exacerbator’ COPD phenotype.,These differences include fewer CD4+ T central memory cells and CD8+ T effector memory cells.,Not applicable. | Patients affected by chronic obstructive pulmonary disease (COPD) have an increased risk of atherothrombotic acute events, independent of smoking and other cardiovascular risk factors.,As a consequence, myocardial ischemia is a relevant cause of death in these patients.,We reviewed studies concerning the potential mechanisms of atherothrombosis in COPD.,Bronchial inflammation spreads to the systemic circulation and is known to play a key role in plaque formation and rupture.,In fact, C-reactive protein blood levels increase in COPD and provide independent prognostic information.,Systemic inflammation is the first cause of the hypercoagulable state commonly observed in COPD.,Furthermore, hypoxia is supposed to activate platelets, thus accounting for the increased urinary excretion of platelet-derived thromboxane in COPD.,The potential metabolic risk in COPD is still debated, in that recent studies do not support an association between COPD and diabetes mellitus.,Finally, oxidative stress contributes to the pathogenesis of COPD and may promote oxidation of low-density-lipoproteins with foam cells formation.,Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by attenuating systemic inflammation, but this benefit needs confirmation in ongoing randomized controlled trials.,Physicians approaching COPD patients should always be aware of the systemic vascular implications of this disease. | 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. | This report updates surveillance results for COPD in the United States.,For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed.,In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD.,From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019).,In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD.,From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001).,In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD.,Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033).,There were 133,575 deaths (63.1 per 100,000) from COPD in 2010.,The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163).,Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001).,Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed.,Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. | 1 |
The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs. | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease responsible for the deaths of 3 million people worldwide in 2005, and predicted to be the third leading cause of death worldwide by 2030.,Many COPD models developed to date have followed a Markov structure, in which patients or populations can move between defined health states over successive time periods or cycles.,In COPD, health states are typically based on disease severity defined solely by lung function, as described by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,These current modelling methods may restrict the ability to reflect the disease progression/clinical pathway or clinical practice.,Given these limitations in previous COPD models, the authors aimed to develop a more flexible model that could improve on the description of the clinical disease pathway.,The overall objective of this model was to inform the development of policies, guidelines or cost-effectiveness analyses.,A second objective was to validate the model in relation to existing epidemiology studies of COPD.,A patient simulation model was developed in Microsoft Excel™.,The predictability of the model was tested by populating it with data from natural history of disease studies as well as with clinical trial data.,Each patient moves through the model with demographic characteristics randomly generated from a set distribution.,These characteristics determine the risk of clinical events occurring in the model.,The validation with these studies found the model to have generally good predictive ability, yielding in this way a good degree of external validity.,The micro-simulation model is a flexible approach for modelling COPD that allows consideration of complex COPD treatment pathways.,The model was found to be generally robust in terms of predicting clinical outcomes of published studies when tested against other studies.,It has significant potential as a tool for supporting future COPD treatment positioning decisions as well as to inform the development of policies, guidelines or cost-effectiveness analyses. | 1 |
Indacaterol is a once-daily long-acting inhaled β2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD).,The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1) with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies.,We considered alternative methods of analysis.,We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol.,This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates.,The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies.,These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 μg once daily, and showed that doses of 75 μg and above achieved clinically important improvements in predicted trough FEV1 response.,Indacaterol 75 μg achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ≥120 mL vs placebo), with a 90% probability that the mean improvement vs placebo exceeded the MCID.,Indacaterol 150 μg achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID).,Indacaterol 300 μg was the lowest dose that achieved the model-predicted maximum trough response.,The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 μg once daily.,This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation.,Comprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 μg is the minimum effective dose, and that 150 and 300 μg are expected to provide optimal bronchodilation, particularly in patients with severe disease. | Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD).,This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.,Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms).,Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.,Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 μg o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study.,Trough FEV1 (LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001).,Trough FEV1 after one dose was significantly higher with indacaterol than placebo (p < 0.001).,Indacaterol demonstrated significantly higher peak FEV1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively.,Standardised AUC measurements for FEV1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively.,Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001).,The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%).,One patient died in the placebo group.,Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.,Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.,NCT00624286 | 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD. | There is a need to identify individuals with COPD at risk for disease progression and mortality.,Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation.,We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling.,Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort.,Validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used.,Multivariate models were used to assess the prognostic value of these biomarkers.,Thirty subjects (3.0 %) died during follow-up.,Non-survivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers.,All collagen biomarkers were significantly elevated in non-survivors compared to survivors.,Mortality risk was significantly increased for subjects with collagen remodeling biomarkers in the upper quartile, especially for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 % confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant confounders.,Serological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD.,NCT00292552, GSK Study No.,SCO104960.,The online version of this article (doi:10.1186/s12931-016-0440-6) contains supplementary material, which is available to authorized users. | 1 |
In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted.,A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol.,Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations.,Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol).,Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD.,Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials.,When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters), the following mean differences (95% confidence interval) were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, −0.005 (−0.077 to 0.067), and indacaterol 150 mcg versus olodaterol 5 mcg, 0.020 (−0.036 to 0.077); trials with concomitant tiotropium: indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (−0.043 to 0.042).,In sensitivity analyses of the full network, results for change from baseline in trough FEV1 favored indacaterol, but this dataset suffered from trial design heterogeneity.,For the other endpoints investigated, no statistically significant differences were found when analyzed in the full network.,When compared under similar trial conditions, olodaterol and indacaterol have similar efficacy in patients with COPD.,This research highlights the importance of considering the concomitant COPD medication when evaluating treatment effects in COPD. | The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β2 agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD).,Seventy-two patients with stable COPD treated with tiotropium (n = 41) or salmeterol (n = 31) were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George’s Respiratory Questionnaire (SGRQ) before and 2-3 months following treatment with tiotropium or salmeterol.,They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group) and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed.,Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype.,Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes.,These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further improvement of exercise capacity and health-related quality of life. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer.,A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins.,This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients.,We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA).,We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose).,To assess residual confounding, a negative control exposure was used to test the validity of our results.,All exposure variables were time-dependent.,The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female.,There were 12,469 patients who received at least one statin prescription.,Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant.,Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99).,Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10).,The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer.,While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy. | 1 |
Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement.,The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT).,Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden.,Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables.,Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments.,Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] −0.07 [−0.13 to −0.02]), EQ-5D VAS (−5.17 [−9.42 to −0.92]), and CAT (3.78 [2.35 to 5.20]).,Musculoskeletal symptoms were significantly associated with worse EQ-5D index (−0.08 [−0.14 to −0.02]), osteoporosis with worse EQ-5D VAS (−4.65 [−9.27 to −0.03]), and depression with worse EQ-5D index (−0.10 [−0.17 to −0.04]).,In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients.,The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD.,Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL.,We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD. | As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy.,Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive.,This led to the question of whether a responsive subset existed that could be investigated further.,The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.,The pooled analysis included 2686 randomized patients.,Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026).,Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014).,The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).,This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS.,These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.,ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729. | 1 |
The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD).,In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end.,The longitudinal changes in St George’s Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1).,The subjects were classified into the rapid decliners, slow decliners, and sustainers based on ΔFEV1/year.,The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile).,In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners.,Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index.,Larger reversibility was related to symptom component improvement.,Of the follow-up data, ΔFEV1/year was the best predictor for worsening of the components of SGRQ.,Continuous smoking was another factor for worsening of the activity component.,For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement.,The longitudinal changes of quality of life and their determinants are markedly different and independent between its components.,The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment. | Health-related quality of life (HRQL) is an important patient-reported outcome for chronic obstructive pulmonary disease (COPD).,We developed models predicting chronic respiratory questionnaire (CRQ) dyspnoea, fatigue, emotional function, mastery and overall HRQL at 6 and 24 months using predictors easily available in primary care.,We used the “least absolute shrinkage and selection operator” (lasso) method to build the models and assessed their predictive performance.,Results were displayed using nomograms.,For each domain-specific CRQ outcome, the corresponding score at baseline was the best predictor.,Depending on the domain, these predictions could be improved by adding one to six other predictors, such as the other domain-specific CRQ scores, health status and depression score.,To predict overall HRQL, fatigue and dyspnoea scores were the best predictors.,Predicted and observed values were on average the same, indicating good calibration.,Explained variance ranged from 0.23 to 0.58, indicating good discrimination.,To predict COPD-specific HRQL in primary care COPD patients, previous HRQL was the best predictor in our models.,Asking patients explicitly about dyspnoea, fatigue, depression and how they cope with COPD provides additional important information about future HRQL whereas FEV1 or other commonly used predictors add little to the prediction of HRQL. | 1 |
Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and cardiovascular diseases (CVDs) share common risk factors.,However, the association between ACOS and the incidence of CVDs has not been reported.,This study investigated the relationship between CVDs and ACOS in the general population.,Data were obtained from Taiwan’s National Health Insurance Research Database for the period 2000 to 2010.,The ACOS cohort comprised patients (n=5814) who had received a diagnosis of asthma and COPD.,The non-ACOS cohort comprised patients who had not received a diagnosis of asthma or COPD and were matched to the ACOS cohort (2:1) by age, sex and index date (n=11 625).,The cumulative incidence of CVDs-coronary artery disease (CAD), cardiac dysrhythmia (CD) and heart failure (HF)-was calculated.,Cox proportional regression analysis was employed to examine the relationship between ACOS and CVDs.,After adjustment for multiple confounding factors-age, sex, comorbidities and medications-patients with ACOS were associated with a significantly higher risk of CVDs; the adjusted HRs (aHRs; 95% CI) for CAD, CD and HF were 1.62 (1.50 to 1.76), 1.44 (1.30 to 1.61) and 1.94 (1.73 to 2.19), respectively, whereas those of beta-blockers treatment for CAD, CD and HF were 1.19 (0.92 to 1.53), 0.90 (0.56 to 1.45) and 0.82 (0.49 to 1.38).,The aHR of atenolol treatment for CD was 1.72 (1.01 to 2.93).,The aHRs (95% CIs) of ACOS without acute exacerbation of COPD (AE-COPD) for CAD, CD and HF were 1.85 (1.70 to 2.01), 1.57 (1.40 to 1.77) and 2.07 (1.82 to 2.35), respectively.,ACOS was associated with higher CVD risk, even without the presence of previous comorbidities or AE-COPD.,No significant differences in CVD events were observed in the ACOS cohort using beta-blockers, except for those using atenolol for treating CD. | 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. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Few studies have focused on the quality of life (QoL) associated medical costs for COPD in China.,A cross-sectional survey of 678 COPD patients was conducted in four major cities (Beijing, Shanghai, Guangzhou and Chengdu), China, in 2011.,Data on socio-demographic information, health conditions and medical costs were collected through a face-to-face interview combined with medical record searching.,The EuroQol (EQ-5D) health questionnaire was applied to assess the QoL of COPD patients.,Among 678 patients with COPD, nearly 40% had difficulties in mobility, usual activities and pain/discomfort, one third had various degrees of anxiety/depression, and one fifth had difficulties in self-care.,The COPD patients had a median utility score of 0.768 and a median visual analog scale score of 70.,The degree of difficulties in any dimensions significantly increased, and utility and health scores decreased with severity of the disease.,Age, gender and disease severity were significantly associated with the quality of life after taking other covariates into consideration.,Poorer QoL was a significant indicator of higher direct medical costs for COPD patients.,Impaired quality of life was significantly linked to increased medical costs for COPD patients and could be an important measure for policy- and decision-making in COPD care. | 1 |
Individuals with chronic obstructive pulmonary disease (COPD) are usually > 50 years of age and have a low body mass index (BMI).,An imbalance between matrix metalloproteinases (MMPs), including MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1), play a role in tissue degradation of lung extracellular matrix among COPD individuals.,The purpose of the present study was to correlate age and/or BMI with salivary levels of MMP-3 and TIMP-1 among Indonesian subjects with COPD.,Thirty COPD patients were recruited to undergo thorough physical assessment and saliva collection for evaluating TIMP-1 and MMP-3 levels using commercially available kits enzyme-linked immunosorbent assay method.,The mean (standard deviation) participant age and BMI were 60.5 (8.13) years, and 23.1 (4.75) kg/m2, respectively.,Furthermore, the mean (standard deviation) of TIMP-1 and MMP3 levels were 23.99 (6.85) ng/mL and 1.81 (1.167) μM, respectively.,Age was negatively correlated with MMP-3 (P < 0.05), but not with TIMP-1 levels.,Age and BMI were not correlated with TIMP-1 level (P > 0.05).,Collectively, this study demonstrated that age has a negative correlation with the protease marker (i.e.,MMP-3), but not the anti-protease marker (TIMP-1).,BMI was not correlated with either protease/anti-protease marker among Indonesian subjects with COPD. | Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis.,The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).,Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).,Plasma levels of MMP-1, MMP-7, MMP-9, and MMP-9/TIMP-1 and CRP were higher in BE and TS than in the NS healthy women (p <0.01).,An inverse correlation between MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP plasma concentrations and FEV1 was observed.,Increase of MMPs and CRP plasma concentrations in BE suggests a systemic inflammatory phenomenon similar to that observed in COPD associated to tobacco smoking, which may also play a role in COPD pathogenesis. | 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.