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Transforming growth factor (TGF)-β is an evolutionarily conserved pleiotropic factor that regulates a myriad of biological processes including development, tissue regeneration, immune responses, and tumorigenesis.,TGF-β is necessary for lung organogenesis and homeostasis as evidenced by genetically engineered mouse models.,TGF-β is crucial for epithelial-mesenchymal interactions during lung branching morphogenesis and alveolarization.,Expression and activation of the three TGF-β ligand isoforms in the lungs are temporally and spatially regulated by multiple mechanisms.,The lungs are structurally exposed to extrinsic stimuli and pathogens, and are susceptible to inflammation, allergic reactions, and carcinogenesis.,Upregulation of TGF-β ligands is observed in major pulmonary diseases, including pulmonary fibrosis, emphysema, bronchial asthma, and lung cancer.,TGF-β regulates multiple cellular processes such as growth suppression of epithelial cells, alveolar epithelial cell differentiation, fibroblast activation, and extracellular matrix organization.,These effects are closely associated with tissue remodeling in pulmonary fibrosis and emphysema.,TGF-β is also central to T cell homeostasis and is deeply involved in asthmatic airway inflammation.,TGF-β is the most potent inducer of epithelial-mesenchymal transition in non-small cell lung cancer cells and is pivotal to the development of tumor-promoting microenvironment in the lung cancer tissue.,This review summarizes and integrates the current knowledge of TGF-β signaling relevant to lung health and disease. | Pulmonary emphysema is characterized by the irreversible loss of pulmonary alveoli.,Despite recent advances in the understanding this disease, its treatment remains palliative.,In this review, we will successively review the data suggesting (1) that alveolar regeneration systems are functional in the mammalian lung and have the potential to regrow lost alveoli, (2) that cigarette smoke, the main etiologic factor of emphysema, inhibits those systems under experimental conditions, and (3) that alveolar regeneration systems are dysfunctional in the human emphysematous lung and may be a target for therapeutic intervention in this disease.,Special emphasis will be put on the role of alveolar fibroblasts in those processes. | 1 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | The best method for expressing lung function impairment is undecided.,We tested in a population of patients with chronic obstructive pulmonary disease (COPD) whether forced expiratory volume in 1 second (FEV1) or FEV1 divided by height squared (FEV1/ht2) was better than FEV1 percent predicted (FEV1PP) for predicting survival.,FEV1, FEV1PP, and FEV1/ht2 recorded post bronchodilator were compared as predictors of survival in 1095 COPD patients followed for 15 years.,A staging system for severity of COPD was defined from FEV1/ht2 and compared with the Global Initiative for Obstructive Lung Disease (GOLD) staging system.,FEV1/ht2 was a better univariate predictor of survival in COPD than FEV1 and both were better than FEV1PP.,The best multivariate model for predicting survival included FEV1/ht2, age and sex.,Comparing the GOLD stages with the FEV1/ht2 groups found that survival was more coherent within each FEV1/ht group than it was within each GOLD stage.,FEV1/ht2 had 60% more people in its most severe group than the severest GOLD stage with these extra subjects having equivalently poor survival and had 155% more in the least severe group with equivalent survival.,GOLD staging misclassified 51% of subjects with regard to survival.,We conclude that GOLD criteria using FEV1PP do not optimally stage COPD with regard to survival.,An alternative strategy using FEV1/ht2 improves the staging of this disease.,Studies which stratify COPD patients to determine the effect of interventions such as drug trials, rehabilitation, or management guidelines should consider alternatives to the GOLD classification. | 1 |
Current conceptual models of health literacy (HL) illustrate the link between HL and health outcomes.,However, these models fail to recognize and integrate certain elements of disease management, health system factors, and socio-demographic factors into their framework.,This article outlines the development of Chronic Airway Disease (CAD) Management and Health Literacy (CADMaHL) conceptual model that integrates the aforementioned elements and factors into a single framework.,Information obtained during the following stages informed the development of our model: (1) a systematic review of existing CAD HL measurement tools that apply core HL domains; (2) patient-oriented focus group sessions to understand HL barriers to CAD self-management practices; (3) key-informant interviews to obtain potential strategies to mitigate CAD management barriers, and validate disease self-management topics; (4) elicited the perspectives of Canadian respirologist’s on the ideal functional HL skills for asthma and COPD patients.,Throughout the study process many stakeholders (i.e., patients, key-informants, and an international HL advisory panel) contributed to and reviewed the model.,The process enabled us to organize the CADMaHL model into 6 primary modules, including: INPUT, consisting of four HL core components (access, understand, communicate, evaluate,) and numeracy skills; OUTPUT, including application of the obtained information; OUTCOME, covering patient empowerment in performing self-management practices by applying HL skills; ASSESSMENT, consisting of information about functionality and relevancy of CADMaHL; IMPACT, including mediators between HL and health outcomes; CROSSCUTTING FACTORS, consisting of diverse socio-demographics and health-system factors with applicability across the HL domains.,We developed the CADMaHL model, with input from key-stakeholders, which addresses a knowledge gap by integrating various disease management, health-system and socio-demographic factors absent from previous published frameworks.,We anticipate that our model will serve as the backbone for the development of a comprehensive HL measurement tool, which may be utilized for future HL interventions for CAD patients.,NCT01474928- Date of registration: 11/26/2017.,The online version contains supplementary material available at 10.1186/s12889-021-10313-x. | Patient education is a key component in the management of chronic obstructive pulmonary disease (COPD).,Delivering effective education to ethnic groups with COPD is a challenge.,The objective of this study was to develop and assess the effectiveness of culturally and linguistically specific audiovisual educational materials in supporting self-management practices in Mandarin- and Cantonese-speaking patients.,Educational materials were developed using participatory approach (patients involved in the development and pilot test of educational materials), followed by a randomized controlled trial that assigned 91 patients to three intervention groups with audiovisual educational interventions and one control group (pamphlet).,The patients were recruited from outpatient clinics.,The primary outcomes were improved inhaler technique and perceived self-efficacy to manage COPD.,The secondary outcome was improved patient understanding of pulmonary rehabilitation procedures.,Subjects in all three intervention groups, compared with control subjects, demonstrated postintervention improvements in inhaler technique (P<0.001), preparedness to manage a COPD exacerbation (P<0.01), ability to achieve goals in managing COPD (P<0.01), and understanding pulmonary rehabilitation procedures (P<0.05).,Culturally appropriate educational interventions designed specifically to meet the needs of Mandarin and Cantonese COPD patients are associated with significantly better understanding of self-management practices.,Self-management education led to improved proper use of medications, ability to manage COPD exacerbations, and ability to achieve goals in managing COPD.,A relatively simple culturally appropriate disease management education intervention improved inhaler techniques and self-management practices.,Further research is needed to assess the effectiveness of self-management education on behavioral change and patient empowerment strategies. | 1 |
Smokers with chronic obstructive pulmonary disease (COPD) seem to be a special subgroup of smokers that have a more urgent need to quit smoking but might find it more difficult to do so.,This study aimed to explore which justifications for tobacco smoking and experiences of quitting were commonly shared in smokers with and without COPD, and which, if any, were specific to smokers with COPD.,In ten primary healthcare centres in the Netherlands, we conducted semi-structured, in-depth interviews in 10 smokers with and 10 smokers without COPD.,Three themes were generated: ‘balancing the impact on health of smoking’, ‘challenging of autonomy by social interference’, ‘prerequisites for quitting’.,All participants trivialized health consequences of smoking; those with COPD seemed to be less knowledgeable about smoking and health.,Both groups of smokers found autonomy very important.,Smokers with COPD were indignant about a perceived lack of empathy in their communication with doctors.,Furthermore, smokers with COPD in particular had little faith in the efficacy of smoking cessation aids.,Lastly, motivation for quitting was dominated by fluctuation and smokers with COPD specifically maintained that their vision of life was linked with quitting.,The participants showed many similarities in their reasoning about smoking and quitting.,The corresponding themes argue for a less paternalistic regime in the communication with smokers with attention required for the motivational stage and room made for smokers’ own views, and with clear information and education.,Furthermore, addressing social interactions, health perceptions and moral agendas in the communication with smokers with COPD may help to make smoking cessation interventions more suitable for them.,The online version of this article (doi:10.1186/s12875-015-0382-y) contains supplementary material, which is available to authorized users. | To unpack and interpret descriptions of experiences of social relationships during pulmonary rehabilitation (PR) for people living with chronic obstructive pulmonary disease (COPD).,Inspired by interpretive phenomenology, individual qualitative interviews were conducted twice with 18 persons from COPD rehabilitation units in two general hospitals.,Qualitative content analysis was performed.,Analysis of the interviews revealed the overarching theme of belonging.,The participants emphasised social integration in rehabilitation groups as well as support from peers and health-care personnel as important dimensions of social relationships with regard to PR.,Active participation in and engagement with the groups provided opportunities for patients to share their knowledge, encouraged mutual trust, and support and increased self-confidence, and motivation for self-care and further social participation.,Integration in the groups and perceived support during PR made coping and adaptation easier and had a positive effect on quality of life.,Patients' perspectives on PR were strongly influenced by certain facets of social relationships, such as social integration and social support.,Patients', peers' and health-care professionals' strategies to promote social support and social integration should be further explored in the future, both in different contexts and for longer periods of time. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | Although international guidelines on pulmonary rehabilitation acknowledge that psychological factors contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD), the few empirical studies investigating this association have found inconsistent results.,The purpose of this study is to investigate whether negative affect and beliefs about exercise of patients with COPD would be related to baseline 6-min walk (6-MW) test results in a pulmonary rehabilitation setting, after correction for physical variables (sex, age, height, weight, and lung function).,A second aim was to examine whether patients' beliefs are associated with treatment outcomes, as measured by an improvement in 6-MW distance.,A 12-week pulmonary rehabilitation program was completed by 166 patients.,Beliefs (perceived necessity and concerns) about exercise and negative affect were assessed by a questionnaire.,Clinical data were obtained from medical records.,Baseline 6-MW distance was positively related to younger age, male gender, better pulmonary function, and having fewer concerns about exercise.,After rehabilitation, patients had increased their walk distance by 12% (32 m), on average.,Baseline physiological and psychological variables were unrelated to patients' response to treatment (increase in walk distance).,However, subgroup analysis showed that for patients with mild to moderate airflow obstruction, concerns about exercise were negatively related to response to treatment.,We conclude that patients' beliefs about the negative consequences of exercise are associated with baseline 6-MW test performance and response to treatment for patients with mild to moderate COPD.,We recommend that patients' concerns about exercise are discussed and, if necessary, corrected during the intake phase. | 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 an inflammatory syndrome that represents an increasing health problem, especially in the elderly population.,Drug therapies are symptomatic and inadequate to contrast disease progression and mortality.,Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets.,Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD.,Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD.,The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes.,Recent evidence corroborating the statement of the “aging theory for COPD” was also discussed. | 1 |
Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend triple therapy (TT) for chronic obstructive pulmonary disease (COPD) patients based on severity.,TT utilization by severity is infrequently studied in real-world settings and may deviate significantly from current clinical recommendations.,This study describes prescribing pathways to TT among patients with COPD in the United States.,This study analyzed Geisinger Health System electronic medical records from 1 January 2004 to 30 November 2016.,Two retrospective cohorts of COPD patients were included: (1) incident COPD, and (2) incident TT users.,COPD treatment patterns, including time to TT, were summarized.,Time to TT was estimated using Kaplan-Meier methods.,Predictors of the relative hazard for TT among incident COPD patients were estimated using Cox proportional hazards regressions.,Incident COPD and TT cohorts included 57,141 and 8173 patients, respectively.,TT was used by 9.6% of incident COPD patients.,In the year before TT, 34.3% of incident TT patients received treatment combinations recommended before TT according to GOLD recommendations, which mainly included: long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs) + LAMAs, and inhaled corticosteroids + LABAs.,Among incident TT patients, median time from COPD diagnosis to TT exceeded 2 years.,The hazard for TT over time was associated with lower forced expiratory volume in 1 s values, more frequent exacerbations, current/previous smoking, and comorbid lung conditions such as pulmonary vascular disease, acute respiratory failure, and lung cancer.,About 15-20% of the incident TT patients stepped down to a one- or two-drug regimen.,Median time to TT discontinuation or step-down were 2 and 9 months, respectively.,The study has revealed discrepancies in the treatment of COPD patients between GOLD guidelines and actual clinical practices in the United States.,Pathways to TT differed from recommended therapy regimes.,Further studies are needed to understand barriers to the use of guideline-recommended TTs by healthcare providers.,The reviews of this paper are available via the supplemental material section. | To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.,This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland.,Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016.,For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline.,We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication.,Groups were compared via ANOVA.,Data of 305 patients (62±7 years, 66% men) were analysed.,In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline.,Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines.,Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively.,Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).,The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups.,The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. | 1 |
Genome-wide mRNA profiling in lung tissue from human and animal models can provide novel insights into the pathogenesis of chronic obstructive pulmonary disease (COPD).,While 6 months of smoke exposure are widely used, shorter durations were also reported.,The overlap of short term and long-term smoke exposure in mice is currently not well understood, and their representation of the human condition is uncertain.,Lung tissue gene expression profiles of six murine smoking experiments (n = 48) were obtained from the Gene Expression Omnibus (GEO) and analyzed to identify the murine smoking signature.,The “human smoking” gene signature containing 386 genes was previously published in the lung eQTL study (n = 1,111).,A signature of mild COPD containing 7 genes was also identified in the same study.,The lung tissue gene signature of “severe COPD” (n = 70) contained 4,071 genes and was previously published.,We detected 3,723 differentially expressed genes in the 6 month-exposure mice datasets (FDR <0.1).,Of those, 184 genes (representing 48% of human smoking) and 1,003 (representing 27% of human COPD) were shared with the human smoking-related genes and the COPD severity-related genes, respectively.,There was 4-fold over-representation of human and murine smoking-related genes (P = 6.7 × 10−26) and a 1.4 fold in the severe COPD -related genes (P = 2.3 × 10−12).,There was no significant enrichment of the mice and human smoking-related genes in mild COPD signature.,These data suggest that murine smoke models are strongly representative of molecular processes of human smoking but less of COPD. | COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | 1 |
The prevalence of pulmonary embolism (PE) in the acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is highly controversial.,We conducted a systematic review and meta-analysis to summarize the epidemiology and characteristics of PE with AE-COPD for current studies.,We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies published prior to October 21, 2020.,Pooled proportions with 95% confidence intervals (95% CIs) were calculated using a random effects model.,Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals were used as effect measures for dichotomous and continuous variables, respectively.,A total of 17 studies involving 3170 patients were included.,The prevalence of PE and deep vein thrombosis (DVT) in AE-COPD patients was 17.2% (95% CI: 13.4%-21.3%) and 7.1% (95% CI: 3.7%-11.4%%), respectively.,Dyspnea (OR = 6.77, 95% CI: 1.97-23.22), pleuritic chest pain (OR = 3.25, 95% CI: 2.06-5.12), lower limb asymmetry or edema (OR = 2.46, 95% CI:1.51-4.00), higher heart rates (MD = 20.51, 95% CI: 4.95-36.08), longer hospital stays (MD = 3.66, 95% CI: 3.01-4.31) were associated with the PE in the AE-COPD patients.,Levels of D-dimer (MD = 1.51, 95% CI: 0.80-2.23), WBC counts (MD = 1.42, 95% CI: 0.14-2.70) were significantly higher and levels of PaO2 was lower (MD = -17.20, 95% CI: -33.94- -0.45, P<0.05) in the AE-COPD with PE group.,The AE-COPD with PE group had increased risk of fatal outcome than the AE-COPD group (OR = 2.23, 95% CI: 1.43-3.50).,The prevalence of PE during AE-COPD varies considerably among the studies.,AE-COPD patients with PE experienced an increased risk of death, especially among the ICU patients.,Understanding the potential risk factors for PE may help clinicians identify AE-COPD patients at increased risk of PE.,CRD42021226568. | Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD).,The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations.,This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD.,8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured.,Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold.,Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs).,Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively).,The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations.,There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level.,Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile.,Rate and risk of exacerbations was higher in patients with higher fibrinogen levels.,This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes.,Trial registration: NCT02164513,The online version contains supplementary material available at 10.1186/s12931-021-01706-y. | 1 |
Pulmonary rehabilitation (PR) is effective in reducing symptoms and improving health status, and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD).,The coronavirus disease 19 (COVID-19) pandemic has greatly impacted PR programs and their delivery to patients.,Owing to fears of viral transmission and resultant outbreaks of COVID-19, institution-based PR programs have been forced to significantly reduce enrolment or in some cases completely shut down during the pandemic.,As a majority of COPD patients are elderly and have multiple co-morbidities including cardiovascular disease and diabetes, they are notably susceptible to severe complications of COVID-19.,As such, patients have been advised to stay at home and avoid social contact to the maximum extent possible.,This has increased patients’ vulnerability to physical deconditioning, depression, and social isolation.,To address this major gap in care, some traditional hospital or clinic-centered PR programs have converted some or all of their learning contents to home-based telerehabilitation during the pandemic.,There are, however, some significant barriers to this approach that have impeded its implementation in the community.,These include variable access and use of technology (by patients), a lack of standardization of methods and tools for evaluation of the program, and inadequate training and resources for health professionals in optimally delivering telerehabilitation to patients.,There is a pressing need for high-quality studies on these modalities of PR to enable the successful implementation of PR at home and via teleconferencing technologies.,Here, we highlight the importance of telerehabilitation of patients with COPD in the post-COVID world and discuss various strategies for clinical implementation. | Pulmonary rehabilitation is widely advocated for people with chronic obstructive pulmonary disease (COPD) to improve exercise capacity, symptoms and quality of life, however only a minority of individuals with COPD are able to participate.,Travel and transport are frequently cited as barriers to uptake of centre-based programs.,Other models of pulmonary rehabilitation, including home-based programs, have been proposed in order to improve access to this important treatment.,Previous studies of home-based pulmonary rehabilitation in COPD have demonstrated improvement in exercise capacity and quality of life, but not all elements of the program were conducted in the home environment.,It is uncertain whether a pulmonary rehabilitation program delivered in its entirety at home is cost effective and equally capable of producing benefits in exercise capacity, symptoms and quality of life as a hospital-based program.,The aim of this study is to compare the costs and benefits of home-based and hospital-based pulmonary rehabilitation for people with COPD.,This randomised, controlled, equivalence trial conducted at two centres will recruit 166 individuals with spirometrically confirmed COPD.,Participants will be randomly allocated to hospital-based or home-based pulmonary rehabilitation.,Hospital programs will follow the traditional outpatient model consisting of twice weekly supervised exercise training and education for eight weeks.,Home-based programs will involve one home visit followed by seven weekly telephone calls, using a motivational interviewing approach to enhance exercise participation and facilitate self management.,The primary outcome is change in 6-minute walk distance immediately following intervention.,Measurements of exercise capacity, physical activity, symptoms and quality of life will be taken at baseline, immediately following the intervention and at 12 months, by a blinded assessor.,Completion rates will be compared between programs.,Direct healthcare costs and indirect (patient-related) costs will be measured to compare the cost-effectiveness of each program.,This trial will identify whether home-based pulmonary rehabilitation can deliver equivalent benefits to centre-based pulmonary rehabilitation in a cost effective manner.,The results of this study will contribute new knowledge regarding alternative models of pulmonary rehabilitation and will inform pulmonary rehabilitation guidelines for COPD.,ClinicalTrials.gov: NCT01423227. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction.,This study aimed to investigate if the combination of two serological biomarkers evaluating these pathological processes could improve the prediction of mortality risk compared to single biomarkers.,Matrix metalloproteinase-mediated degradation of the type IV collagen α3 chain (C4Ma3), located in the alveolar basement membrane, and plasmin-mediated degradation of crosslinked fibrin (X-FIB), an end-product of fibrinogen, were assessed serologically in a subset of the ECLIPSE cohort (n = 982).,Biomarker data were dichotomized into high versus low at the median.,Cox regression and Kaplan-Meier curves were used to analyze the predictive value of having one or two high biomarkers for all-cause mortality over two years.,COPD participants with high levels of two biomarkers were at significantly higher risk of all-cause mortality with a hazard ratio of 7.66 (95% CI 1.75-33.48; p = 0.007) while participants with one high biomarker were not at significantly higher risk (HR 3.79 [95% CI 0.85-16.94]; p = 0.08).,A combination of serological biomarkers of alveolar basement membrane destruction and clot resolution was predictive of all-cause mortality in COPD.,The combination of two different pathological aspects may strengthen prognostic accuracy and could be used in conjunction with clinical assessment to guide treatment decisions. | Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations.,However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.,Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed.,Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC).,The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations.,Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.,Compared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively).,In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC.,Neither FEV1 nor FVC was associated with cardiovascular risk.,Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).,Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks. | 1 |
Dysregulated lipid metabolism plays crucial roles in various diseases, including diabetes mellitus, cancer, and neurodegeneration.,Recent studies suggest that alterations in major lipid metabolic pathways contribute to pathogenesis of lung diseases, including chronic obstructive pulmonary disease (COPD).,These changes allow lung tissue to meet the energy needs and trigger anabolic pathways that initiate the synthesis of active molecules directly involved in the inflammation.,In this review, we summarize the changes of catabolism and anabolism of lipids, lipid molecules including lipid mediators, lipid synthesis transcription factors, cholesterol, and phospholipids, and how those lipid molecules participate in the initiation and resolution of inflammation in COPD. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
Guidelines recommendations for the treatment of COPD are poorly followed.,This could be related to the complexity of classification and treatment algorithms.,The purpose of this study was to validate a simpler dyspnea-based treatment algorithm for inhaled pharmacotherapy in stable COPD, comparing its concordance with the current Global Initiative for Obstructive Lung Disease (GOLD) guideline.,We enrolled patients who had been diagnosed with COPD in three primary care facilities and two tertiary hospitals in Spain.,We determined anthropometric data, forced expiratory volume in the 1st second (percent), exacerbations, and dyspnea based on the modified Medical Research Council scale.,We evaluated the new algorithm based on dyspnea and exacerbations and calculated the concordance with the current GOLD recommendations.,We enrolled 100 patients in primary care and 150 attending specialized care in a respiratory clinic.,There were differences in the sample distribution between cohorts with 41% vs 26% in grade A, 16% vs 12% in grade B, 16% vs 22% in grade C, and 27% vs 40% in grade D for primary and respiratory care, respectively (P=0.005).,The coincidence of the algorithm with the GOLD recommendations in primary care was 93% and 91.8% in the respiratory care cohort.,A simple dyspnea-based treatment algorithm for inhaled pharmacotherapy of COPD could be useful in the management of COPD patients and concurs very well with the recommended schema suggested by the GOLD initiative. | Introduction: Inhaled corticosteroids (ICS) (in fixed combinations with long-acting β2-agonists [LABAs]) are frequently prescribed for patients with chronic obstructive pulmonary disease (COPD), outside their labeled indications and recommended treatment strategies and guidelines, despite having the potential to cause significant side effects.,Areas covered: Although the existence of asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS monotherapy is usually not indicated for COPD), the current level of ICS/LABA use is not consistent with the prevalence of ACOS in the COPD population.,Data have recently become available showing the comparative efficacy of fixed bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with ICS/LABA combinations).,Additionally, new information has emerged on ICS withdrawal without increased risk of exacerbations, under cover of effective bronchodilation.,Expert opinion: For patients with COPD who do not have ACOS, a LAMA/LABA combination may be an appropriate starting therapy, apart from those with mild disease who can be managed with a single long-acting bronchodilator.,Patients who remain symptomatic or present with exacerbations despite effectively delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or phosphodiesterase-4 inhibitors.,When prescribing an ICS/LABA, the risk:benefit ratio should be considered in individual patients. | 1 |
Incorrect use of inhalers is very common and subsequently leads to poor control of COPD.,Among health care providers, pharmacists are in the best position to educate patients about the correct use of inhaler devices.,The objective of this study was to evaluate the impact of pharmacist-led training on the improvement of inhaler technique for COPD patients in Vietnam.,For this pre- and post-intervention study, standardized checklists of correct use of metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) were used to evaluate the inhaler technique.,A scoring system (maximum score =8) was applied before and after training to guarantee assessment uniformity among pharmacists.,Three methods including “face-to-face training”, “teach-back” and “technique reminder label” were used.,After the baseline evaluation (T0), the inhaler technique was reassessed after 1 month (T1), 3 months (T2), 6 months (T3) and 12 months (T4).,A total of 211 COPD patients participated in the study.,Before the training, a high rate of errors was recorded.,After the training, the percentage of patients using MDIs and DPIs perfectly increased significantly (p<0.05).,The mean technique score for MDIs and DPIs improved from 6.0 (T0) to 7.5 (T3) and 6.9 (T4) and 6.7 (T0) to 7.6 (T3) and 7.2 (T4), respectively (p<0.05).,The average training time was 6 minutes (T0) and 3 minutes (T3), respectively.,Pharmacist-led comprehensive inhaler technique intervention program using an unbiased and simple scoring system can significantly improve the inhaler techniques in COPD patients.,Our results indicated a 3-month period as the optimal time period between training and retraining for maintaining the correct inhaler technique.,The training would be highly feasible and suitable for implementing in the clinical setting.,Our model of pharmacist-led training should be considered as an effective solution for managing COPD patients and better utilization of health care human resources, especially in a developing country like Vietnam. | The economic burden of COPD has not been well studied in China.,This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.,A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011.,The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation).,Logistic regression model was used to explore factors related to high total costs on COPD.,The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively.,The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China.,Hospitalization accounted for 56.7% of the total costs.,High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.,COPD posed a heavy economic burden in China.,Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care. | 1 |
Pulmonary tuberculosis (PTB) is a risk factor for COPD, but the clinical characteristics and the chest imaging features (emphysema and bronchiectasis) of COPD with previous PTB have not been studied well.,The presence, distribution, and severity of emphysema and bronchiectasis in COPD patients with and without previous PTB were evaluated by high-resolution computed tomography (HRCT) and compared.,Demographic data, respiratory symptoms, lung function, and sputum culture of Pseudomonas aeruginosa were also compared between patients with and without previous PTB.,A total of 231 COPD patients (82.2% ex- or current smokers, 67.5% male) were consecutively enrolled.,Patients with previous PTB (45.0%) had more severe (p=0.045) and longer history (p=0.008) of dyspnea, more exacerbations in the previous year (p=0.011), and more positive culture of P. aeruginosa (p=0.001), compared with those without PTB.,Patients with previous PTB showed a higher prevalence of bronchiectasis (p<0.001), which was more significant in lungs with tuberculosis (TB) lesions, and a higher percentage of more severe bronchiectasis (Bhalla score ≥2, p=0.031), compared with those without previous PTB.,The overall prevalence of emphysema was not different between patients with and without previous PTB, but in those with previous PTB, a higher number of subjects with middle (p=0.001) and lower (p=0.019) lobe emphysema, higher severity score (p=0.028), higher prevalence of panlobular emphysema (p=0.013), and more extensive centrilobular emphysema (p=0.039) were observed.,Notably, in patients with TB lesions localized in a single lung, no difference was found in the occurrence and severity of emphysema between the 2 lungs.,COPD patients with previous PTB had unique features of bronchiectasis and emphysema on HRCT, which were associated with significant dyspnea and higher frequency of severe exacerbations.,While PTB may have a local effect on bronchiectasis, its involvement in airspace damage in COPD may be extensive, probably through interactions with cigarette smoke. | 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 |
The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting β2 agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD).,This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4) inhibitor frequently used by patients with COPD and cardiovascular comorbidities.,Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 μg or UMEC 500 μg/VI 25 μg.,All subjects received a single tablet containing 240 mg verapamil on each of days 9-13.,Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated.,There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone.,UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold) was observed with verapamil.,Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination.,Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug.,The UMEC/VI combination is unlikely to have a clinically meaningful drug-drug interaction with moderate P-glycoprotein transporter and CYP3A4 inhibitor drugs. | Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002.,We sought to update an evaluation of the safety of tiotropium in the HandiHaler® formulation as significant clinical trial data have become available over time.,Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler® clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 μg once-daily dosing, COPD indication, duration of at least four weeks.,Incidence rates by treatment group, rate differences (tiotropium-placebo), and 95% confidence intervals were determined.,Twenty-six trials were identified involving 17,014 patients.,Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men.,Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo).,Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (−17.5 [−22.9, −12.2]), serious adverse event (−1.41 [−2.81, −0.00]) and a fatal event (−0.63 [−1.14, −0.12]).,A reduced risk was present for adverse events that were cardiac (−0.79 [−1.48, −0.09]), lower respiratory (−14.2 [−17.0, −11.5]) and for a composite endpoint of major adverse cardiovascular events (−0.45 [−0.85, −0.05]).,Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.,The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation.,Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown.,To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD.,Subjects with asthma and COPD (n = 54 and n = 49) were studied.,Clinical characteristics and sputum were collected at entry into the study.,A 2-step sputum processing method was performed for supernatant and cytospin preparation.,Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels.,Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17.,There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02].,In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes.,However, these phenotypes were unrelated to the diagnosis of asthma or COPD.,Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique.,Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease.,Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
In China, the burden of chronic obstructive disease (COPD) is high in never-smokers but little is known about its causes in this group.,We analysed data on 287 000 female and 30 000 male never-smokers aged 30-79 years from 10 regions in China, who participated in the China Kadoorie Biobank baseline survey (2004-2008).,Prevalence of airflow obstruction (AFO) (pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and below the lower limit of normal (LLN)) was estimated, by age and region.,Cross-sectional associations of AFO (FEV1/FVC <0.7), adjusted for confounding, were examined.,AFO prevalence defined as FEV1/FVC <0.7 was 4.0% in females and 5.1% in males (mean ages 51 and 54 years, respectively).,AFO prevalence defined as FEV1/FVC <LLN was 5.9% and 5.2%, respectively.,In females, odds ratios of AFO were positively associated with lower household income (1.63, 95% CI 1.55-1.72 for lowest versus highest income groups), prior tuberculosis (2.36, 95% CI 2.06-2.71), less education (1.17, 95% CI 1.12-1.23 for no schooling versus college education), rural region and lower body mass index.,AFO was positively associated with cooking with coal but not with other sources of household air pollution.,Associations were similar for males.,AFO is prevalent in Chinese never-smokers, particularly among those with low socioeconomic status or prior tuberculosis, and in rural males.,Airflow obstruction is prevalent in Chinese never-smokers and particularly associated with low socioeconomic statushttp://ow.ly/sG481 | Chronic obstructive pulmonary disease (COPD) is the 13th leading cause of burden of disease worldwide and is expected to become 5th by 2020.,Biomass fuel combustion significantly contributes to COPD, although smoking is recognized as the most important risk factor.,Rural women in developing countries bear the largest share of this burden resulting from chronic exposures to biomass fuel smoke.,Although there is considerable strength of evidence for the association between COPD and biomass smoke exposure, limited information is available on the background prevalence of COPD in these populations.,This study was conducted to estimate the prevalence of COPD and its associated factors among non-smoking rural women in Tiruvallur district of Tamilnadu in Southern India.,This cross-sectional study was conducted among 900 non-smoking women aged above 30 years, from 45 rural villages of Tiruvallur district of Tamilnadu in Southern India in the period between January and May 2007.,COPD assessments were done using a combination of clinical examination and spirometry.,Logistic regression analysis was performed to examine the association between COPD and use of biomass for cooking.,R software was used for statistical analysis.,The overall prevalence of COPD in this study was found to be 2.44% (95% CI: 1.43-3.45).,COPD prevalence was higher in biomass fuel users than the clean fuel users 2.5 vs.,2%, (OR: 1.24; 95% CI: 0.36-6.64) and it was two times higher (3%) in women who spend >2 hours/day in the kitchen involved in cooking.,Use of solid fuel was associated with higher risk for COPD, although no statistically significant results were obtained in this study.,The estimates generated in this study will contribute significantly to the growing database of available information on COPD prevalence in rural women.,Moreover, with concomitant indoor air pollution measurements, it may be possible to increase the resolution of the association between biomass use and COPD prevalence and refine available attributable burden of disease estimates. | 1 |
The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease.,Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema.,We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV1) in the general population.,Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390).,On average 3 FEV1 measurements during 3 surveys, respectively 7 FEV1 measurements during 8 surveys were present.,Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV1 measurements.,In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher FEV1 level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower FEV1 level (p = 0.06).,The associations were even more significant in the pooled cohort analysis.,No significant association of KEAP1 or NFE2L2 SNPs with FEV1 decline was observed.,This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population.,It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of FEV1 in the general population.,It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of FEV1 in the general population. | For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis').,Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases.,We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD).,Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion.,We found a weak association of the 249Ser allele with childhood asthma (p = 0.03).,Yet, significance was lost after Bonferroni correction.,No association was evident for AD or COPD.,Variation in TLR6 might play a role in the pathogenesis of childhood asthma. | 1 |
This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study.,This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries.,The study included patients aged >40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion.,A total of seven Polish centers participated in the study.,Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS).,There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment.,Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression.,Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese.,There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome.,The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic. | Smoking can affect both the phenotypic expression of COPD and factors such as disease severity, quality of life, and comorbidities.,Our objective was to evaluate if the impact of active smoking on these factors varies according to the disease phenotype.,This was a Spanish, observational, cross-sectional, multicenter study of patients with a diagnosis of COPD.,Smoking rates were described among four different phenotypes (non-exacerbators, asthma-COPD overlap syndrome [ACOS], exacerbators with emphysema, and exacerbators with chronic bronchitis), and correlated with disease severity (body mass index, obstruction, dyspnea and exacerbations [BODEx] index and dyspnea grade), quality of life according to the COPD assessment test (CAT), and presence of comorbidities, according to phenotypic expression.,In total, 1,610 patients were recruited, of whom 46.70% were classified as non-exacerbators, 14.53% as ACOS, 16.37% as exacerbators with emphysema, and 22.40% as exacerbators with chronic bronchitis.,Smokers were predominant in the latter 2 groups (58.91% and 57.67%, respectively, P=0.03).,Active smoking was significantly associated with better quality of life and a higher dyspnea grade, although differences were observed depending on clinical phenotype.,Active smoking is more common among exacerbator phenotypes and appears to affect quality of life and dyspnea grade differently, depending on the clinical expression of the disease. | 1 |
Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.,Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.,Methods: Exacerbations and change from baseline in trough FEV1 and St.,George’s Respiratory Questionnaire results were analyzed by prior ICS use.,Exacerbations were also analyzed while excluding data from the first 30 days.,Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P < 0.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P = 0.115).,To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce the annual on-treatment moderate/severe exacerbation rate (19%; P < 0.001) compared with UMEC/VI.,The benefit of FF/UMEC/VI compared with UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P < 0.001; non-ICS users, 35% reduction; P = 0.018), and overall when excluding the first 30 days (29%; P < 0.001).,Improvements from baseline with FF/UMEC/VI compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St.,George’s Respiratory Questionnaire, regardless of prior ICS use.,Conclusions: These data support the important treatment effects of FF/UMEC/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.,Clinical trial registered with www.clinicaltrials.gov (NCT 02164513). | 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. | 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. | Malnutrition is common in patients with COPD; however, little is known about its impacts on health-related quality of life (QoL) among patients with COPD.,This study aimed to explore the nutritional status and dietary intake among outpatients with COPD in Vietnam and its possible associations with QoL.,A cross-sectional study was carried out in COPD outpatients visiting the COPD management unit at the National Lung Hospital, Hanoi, Vietnam between May 2017 and July 2017.,Consecutive outpatients with a confirmed diagnosis of COPD were recruited with written inform consent.,The nutritional status of participants was assessed using Subjective Global Assessment (SGA), and dietary intake via a 24-hour recall interview.,The St George Respiratory Questionnaire (SGRQ) for COPD was used to investigate the participants’ QoL.,Sociodemographic and clinical data were extracted from hospital records.,Of 168 COPD outpatients involved in the study, three-quarters (74.4%) were diagnosed as malnourished (SGA B/C) and 81.5% reported unintentional weight loss.,Most of the patients did not meet their estimated energy and protein requirements (85.7% and 89.9%, respectively).,Malnutrition was significantly associated with disease severity (P=0.039) and ratio of protein intake to estimated requirement (P=0.005).,QoL was low for all levels of malnutrition or disease severity, with well-nourished participants and those with less disease severity having better QoL (P=0.006 and P<0.001, respectively).,With an extra meal per day, the odds of having malnutrition decreased 5.6 times (P<0.05) and the total SGRQ reduced 3.61 scores (P<0.05) indicating a better QoL.,Malnutrition and weight loss are prevalent among COPD outpatients.,Most of the patients had inadequate dietary intake and low QoL.,Nutrition counselling including increasing the number of meals per day with a focus on energy- and protein-rich foods may help improving nutritional status and QoL of patients with COPD in Vietnam. | 1 |
We investigated the effect of the long-acting muscarinic antagonist aclidinium bromide on chronic obstructive pulmonary disease (COPD) exacerbations by pooling data from five randomized, placebo-controlled, parallel-group Phase III studies of 3-6 months’ duration.,Data were pooled from the aclidinium 400 μg twice-daily (BID) and placebo arms (N = 2,521) and stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) group (A, B, C and D).,Results showed that fewer patients experienced ≥1 exacerbation with aclidinium (any severity: 12.5%; moderate to severe: 10.9%) compared with placebo (any severity: 15.7%; moderate to severe: 13.3%) and the odds of experiencing ≥1 exacerbation of any severity were reduced in patients receiving aclidinium (odds ratio = 0.78, p = 0.039).,Furthermore, aclidinium reduced the rate of exacerbations compared with placebo (any severity: rate ratio = 0.79, p = 0.026; moderate to severe: 0.80, p = 0.044).,The time to first exacerbation of any severity was delayed with aclidinium compared with placebo (hazard ratio = 0.79, p = 0.026) and there was a numerical delay in time to first moderate-to-severe exacerbation.,Finally, the effects of aclidinium on exacerbations versus placebo were greater in patients in GOLD Groups B and D; however, it is of note that only 10.7% of patients were classified in Group A or C.,In summary, the results indicate that aclidinium 400 μg BID reduces the frequency of COPD exacerbations compared with placebo and that these effects are greater in symptomatic patients. | 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. | 1 |
Bufei Yishen formula (BYF) is a traditional Chinese medicine formula, which has long been used as a therapeutic agent for the treatment of chronic obstructive pulmonary disease (COPD).,Systems pharmacology has previously been used to identify the potential targets of BYF, and an experimental study has demonstrated that BYF is able to prevent COPD.,In addition, the transcriptomic and metabolomic profiles of lung tissues from rats with COPD and BYF-treated rats have been characterized.,The present study aimed to determine the therapeutic mechanisms underlying the effects of BYF on COPD treatment by integrating transcriptomics, proteomics and metabolomics, together with systems pharmacology datasets.,Initially, the proteomic profiles of rats with COPD and BYF-treated rats were analyzed.,Subsequently, pathway and network analyses were conducted to integrate three-omics data; the results demonstrated that the genes, proteins and metabolites were predominantly associated with oxidoreductase activity, antioxidant activity, focal adhesion and lipid metabolism.,Finally, a comprehensive analysis of systems pharmacology, transcriptomic, proteomic and metabolomic datasets was performed, and numerous genes, proteins and metabolites were found to be regulated in BYF-treated rats; the potential target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhesion.,In conclusion, BYF exerted beneficial effects against COPD, potentially by modulating lipid metabolism, the inflammatory response, oxidative stress and cell junction pathways at the system level. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Pulmonary hypertension (PH) is a common complication of chronic respiratory disease.,Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae.,However, the association between DM and PH in chronic respiratory disease remains unclear.,In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease.,We prospectively analyzed 386 patients in our hospital with chronic respiratory disease.,An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH.,We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH.,Of the 386 patients, 42 (10.9%) were diagnosed as having PH.,The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group.,Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients.,DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease. | Despite the recent increasing worldwide attention towards pulmonary hypertension (PH), its epidemiology remains poorly described in Africa.,Accordingly, we performed a systematic review and meta-analysis of PH prevalence, incidence and etiologies in Africa.,We searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus.,Published observational studies until September 20, 2017, including adult participants residing in Africa were considered.,Two review authors independently selected studies, assessed included studies for methodological quality, and extracted data.,A random-effects model was used for meta-analysis.,Heterogeneity was evaluated by the χ 2 test on Cochrane’s Q statistic which is quantified by I2 values.,Using Newcastle-Ottawa Scale, we considered a score of 0-4, 5-7, and 8-10 as indicative of high, moderate, and low risk of bias in included studies, respectively.,Of 1611 entries, 25 studies were retained.,Twelve (48%), seven (28%), and six (24%) papers had respectively a low, moderate and high risk of bias.,The prevalence of PH widely varied across different populations: 9.8% (95% confidence interval: 3.2-19.3; I2 = 99.4%; 6 studies) in 11,163 people presenting with cardiac complaints; 10.6% (4.3-19.1; I2 = 90.3%; 4 studies) in 937 HIV-infected people; 32.9% (17.6-50.4; I2 = 97.2%; 3 studies) in 2077 patients with heart failure; 23.2% (15.2-32.2; I2 = 59.4%; 3 studies) in 248 patients on hemodialysis; 12.9% (11.8-14.0; I2 = 79.7%; 2 studies) in 3750 patients with rheumatic heart disease; 36.9% (29.7-44.3; I2 = 79.7; 2 studies) in 79 patients with sickle cell disease; 62.7% (49.0-74.7; 1 study) in 51 patients with chronic obstructive pulmonary disease; 25.4% (16.3-37.3; 1 study) in 63 patients with systemic lupus erythematous; 68.7% (62.8-74.1; 1 study) in 259 patients with cardiac surgery; and 7.4% (4.6-11.9; 1 study) in 202 patients with systemic sclerosis.,No study reported PH incidence.,From one international study (n = 209), PH etiologies were: left heart disease (68.9%), pulmonary arterial hypertension (15.8%), lung disease and/or hypoxia (12.0%), chronic thromboembolic PH (1.9%) and unclear/multifactorial PH (15.8%).,The prevalence of PH is relatively high in some populations in Africa, perhaps mainly driven by left heart diseases, highlighting the need for context-specific interventions.,The online version of this article (10.1186/s12890-017-0549-5) contains supplementary material, which is available to authorized users. | 1 |
Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria.,The optimum antibiotic choice remains unknown.,We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo.,This was a single-centre, single-blind, randomised placebo-controlled trial.,Patients aged ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks, doxycycline 100 mg/day, azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks.,The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S quantitative PCR (qPCR), sputum inflammation and antibiotic resistance.,99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed.,After adjustment, there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL (95% CI −0.08 to 0.91, p=0.10) with moxifloxacin, 0.11 (−0.33 to 0.55, p=0.62) with doxycycline and 0.08 (−0.38 to 0.54, p=0.73) with azithromycin from placebo, respectively.,There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation.,More treatment-related adverse events occurred with moxifloxacin.,Of note, mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms.,Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy.,Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.,clinicaltrials.gov (NCT01398072). | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
The major determinant of the decline in lung function, quality of life, and the increased mortality risk in patients with COPD is represented by severe acute exacerbations of the disease, that is, those requiring patients’ hospitalization, constituting a substantial social and health care burden in terms of morbidity and medical resource utilization.,Different long-term therapeutic strategies have been proposed so far in order to prevent and/or reduce the clinical and social impact of these events, the majority of which were extrapolated from trials initially focused on the effect of long-acting muscarinic antagonist and subsequently on the efficacy of long-acting β2-agonists in combination or not with inhaled corticosteroids.,The option to employ all three classes of molecules combined, despite the limited amount of evidence in our possession, represents a choice currently proposed by international guidelines; however, current recommendations are often based mainly on observational studies or on the results of secondary outcomes in randomized controlled trials.,The present narrative review evaluates the available trials that investigated the efficacy of inhaled therapy to prevent COPD exacerbations and especially severe ones, with a particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide fixed dose combination, which is the first treatment that comprises all the three drug classes, specifically tested for the prevention of moderate and severe COPD exacerbations. | Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD.,The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used.,Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS.,The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose.,To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used.,14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS.,On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS.,Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size.,These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk. | 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF).,The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects.,Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology.,Corticosteroids have been widely prescribed for the treatment of asthma, COPD, and IPF.,However, the effectiveness of corticosteroids as an anti-inflammatory drug is limited by steroid resistance in severe asthma, the majority of COPD cases, and pulmonary fibrosis.,There is an urgent medical need to develop target-specific drugs for the treatment of these respiratory conditions.,Oligonucleotide therapies, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) are now being evaluated both pre-clinically and clinically as potential therapeutics.,The mechanisms of action of ASO and siRNA are highly target mRNA specific, ultimately leading to target protein knockdown. miRNA has both biomarker and therapeutic values, and its knockdown by a miRNA antagonist (antagomir) has a broader but potentially more non-specific biological outcome.,This review will compile the current findings of oligonucleotide therapeutic targets, verified in various respiratory disease models and in clinical trials, and evaluate different chemical modification approaches to improve the stability and potency of oligonucleotides for the treatment of respiratory diseases. | Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | 1 |
To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | 1 |
Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover.,Recently, activation of the WNT/β-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases.,We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of β-catenin in fibroblast phenotype and function.,We assessed the expression of WNT-pathway genes and the functional role of β-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD.,Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling.,Stimulation of fibroblasts with TGF-β1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and β-catenin mRNA expression.,The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-β1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar.,Accordingly, TGF-β1 activated β-catenin signaling, as shown by an increase in transcriptionally active and total β-catenin protein expression.,Furthermore, TGF-β1 induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by β-catenin specific siRNA and by pharmacological inhibition of β-catenin, whereas the TGF-β1-induced expression of PAI-1 was not affected.,The induction of transcriptionally active β-catenin and subsequent fibronectin deposition induced by TGF-β1 were enhanced in pulmonary fibroblasts from individuals with COPD.,β-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation.,WNT/β-catenin pathway expression and activation by TGF-β1 is enhanced in pulmonary fibroblasts from individuals with COPD.,This suggests an important role of the WNT/β-catenin pathway in regulating fibroblast phenotype and function in COPD. | 1 |
In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD).,The pathological mechanisms linking MS and COPD are largely unknown.,It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD.,This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD.,Experiments were performed on female C57BL/6 mice.,Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema.,Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated.,Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study.,The CD31+ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3.,GLP-1 reduces the area of emphysema and increases the number of CD31+ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract.,The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism.,EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD.,Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD. | Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | 1 |
Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS).,Recommendations on their diagnosis are diffuse and inconsistent.,This survey aimed to identify consensus on criteria for diagnosing ACOS.,A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists.,Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis.,The two most frequently selected answers were considered as major criteria, others as minor criteria.,The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis.,Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient.,To diagnose ACOS in COPD patients, major criteria were “high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second ≥400 mL)” and “high degree of response to bronchodilators (>200 mL and ≥12% predicted above baseline)”.,Minor criteria were “personal/family history of atopy and/or IgE sensitivity to ≥1 airborne allergen”, “elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide”, “diagnosis of asthma <40 years of age”; “symptom variability”, and “age (in favor of asthma)”.,To diagnose ACOS in asthma patients, major criteria were “persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)” and “exposure to noxious particles/gases, with ≥10 pack-years for (ex-)smokers”; minor criteria were “lack of response on acute bronchodilator test”; “reduced diffusion capacity”; “limited variability in airway obstruction”; “age >40 years”; “emphysema on chest computed tomography scan”.,Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients.,These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. | 1 |
Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) are central to the pharmacological management of COPD.,Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 μg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD.,The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 μg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD.,A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411).,Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs.,Costs are presented in US dollars based on 2015 prices.,The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs).,Costs and outcomes were discounted at a 3% annual rate.,Incremental cost-effectiveness ratios were calculated.,One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results.,UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751).,Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment.,UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses.,Sensitivity analyses confirmed that the results were robust.,The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult.,Incorporation of patient preferences is widely encouraged.,To summarize original research articles determining patient preference in moderate-to-severe disease.,Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma.,The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease.,We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences.,Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion.,Data were tabulated and analyzed descriptively.,About 478 articles identified, 448 were rejected and 30 analyzed.,There were 25 on COPD and five on asthma.,Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability.,Patients strongly preferred sponsors’ inhalers.,At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention.,While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience.,Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler.,Few studies have examined patient preference in these diseases.,More research is needed to fill in knowledge gaps. | 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 |
Quality of life (QoL) has a weak relationship with lung function (LF) impairment in COPD; some cope well despite poor LF, whereas others suffer disproportionate QoL impairment despite well-preserved LF.,Adjuvant non-pharmacological interventions such as rehabilitation and psychological/behavioural support may help if acceptable and targeted appropriately, but they are under-used and sometimes declined by patients.,This study aimed to explore and understand variations in experiences and coping strategies in patients with different severities of disease and disease-specific QoL.,Thirty-four participants were purposively sampled across a spectrum of LF and QoL impairment, to cover a grid of sub-groups (‘very severe LF, good QoL’, moderate LF, poor QoL’ and so on).,Semi-structured interviews, digitally recorded, were analysed by thematic analysis.,Data saturation was achieved.,Four themes emerged: symptom impact, coping strategies, coping challenges and support needs.,Most of them described using multiple coping strategies, yet over half reported significant challenges coping with COPD, including psychological impact, non-acceptance of diagnosis and/or disease progression, effects of co-morbidities and inadequate self-management skills.,Approximately half of the participants wanted further help, ideally non-pharmacological, across all LF impairment groups but mainly with lower QoL.,Those with lower QoL additionally reported greater psychological distress and greater use of non-pharmacological support strategies where accessible.,Patients who develop effective coping strategies have a better QoL independent of objective LF, whereas others cope poorly, are aware of this and report more use of non-pharmacological approaches.,This study suggests that severely impaired QoL, irrelevant of lung function, is a powerful patient-centred indication to explore the positive benefits of psychological and behavioural support for distressed COPD patients. | There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care.,This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors.,Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention.,Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia).,Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD.,Self-care activities evolved spontaneously as participants experienced symptoms of COPD.,However, there was a lack of awareness about whether these strategies would impact upon symptoms.,Perceptions of COPD by family members posed a challenge to self-care for some participants.,Health care professionals should elicit patients’ prior disease experiences and utilize spontaneous attempts at disease management in future self-management.,These findings have implications for promoting self-management and enhancing quality of life. | 1 |
COPD is associated with a large disease burden.,The use of dual (two maintenance treatments) and triple (combination of any three treatments) therapy has shown efficacy for symptom relief; however, some patients with COPD remain symptomatic despite these therapies.,This study assessed the scope and magnitude of the symptomatic burden for patients with COPD receiving dual or triple therapy.,Cross-sectional data from three Adelphi COPD surveys (2013-2016) conducted in the USA, Europe, Japan, and China were analyzed for patients with COPD and forced expiratory volume in 1 second ≤65% receiving dual or triple therapy for ≥3 months.,Physicians completed clinical and disease characteristic forms for identified patients.,Corresponding patients completed questionnaires that included validated survey instruments to assess adherence and symptom impact.,Descriptive statistics are reported.,Our analysis included 690 patients (mean age 68.2 years; 73.3% male); 41.4% and 58.6% were receiving dual and triple therapy, respectively.,Most patients had dyspnea with substantial disability (modified Medical Research Council dyspnea scale rating ≥2, 56.3%; large health status impairment from symptoms, COPD Assessment Test score >20, 64.4%).,A large symptom burden was observed, even for patients highly adherent to treatment (Morisky Medication Adherence Scale 8, 30.3% [185/612]), of whom 62.1% still had a COPD Assessment Test score >20.,Sensitivity analyses of patients regardless of their forced expiratory volume in 1 second status and of those receiving treatment for >6 months both reported similar results.,Although patients who consult their physicians more frequently than average may be overrepresented because of the observational design of this study, we report that unmet needs remain for patients with COPD, despite the use of dual or triple therapy.,A percentage of patients with COPD reported major symptom burden affecting their daily living and causing a large impairment in the health status, regardless of treatment adherence. | The effectiveness of meditative movement (tai chi, yoga, and qigong) on COPD remained unclear.,We undertook a systematic review and meta-analysis to determine the effectiveness of meditative movement on COPD patients.,We searched PubMed, Web of Science, EMBASE, and the Cochrane Center Register of Controlled Trials for relevant studies.,The methods of standard meta-analysis were utilized for identifying relevant researches (until August 2017), quality appraisal, and synthesis.,The primary outcomes were the 6-minute walking distance (6MWD), lung function, and dyspnea levels.,Sixteen studies involving 1,176 COPD patients were included.,When comparing with the control group, the 6MWD was significantly enhanced in the treatment group (3 months: mean difference [MD]=25.40 m, 95% CI: 16.25 to 34.54; 6 months: MD=35.75 m, 95% CI: 22.23 to 49.27), as well as functions on forced expiratory volume in 1 s (FEV1) (3 months: MD=0.1L, 95% CI: 0.02 to 0.18; 6 months: MD=0.18L, 95% CI: 0.1 to 0.26), and FEV1 % predicted (3 months: 4L, 95% CI: 2.7 to 5.31; 6 months: MD=4.8L, 95% CI: 2.56 to 7.07).,Quality of life for the group doing meditative movement was better than the control group based on the Chronic Respiratory Disease Questionnaire dyspnea score (MD=0.9 units, 95% CI: 0.51 to 1.29) and fatigue score (MD=0.75 units, 95% CI: 0.42 to 1.09) and the total score (MD=1.92 units, 95% CI: 0.54 to 3.31).,Meditative movement may have the potential to enhance lung function and physical activity in COPD patients.,More large-scale, well-designed, multicenter, randomized controlled trials should be launched to evaluate the long-range effects of meditative movement. | 1 |
Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD) patients has been well documented, but less is known about the role played by the large airways.,Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients.,The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM) area and the extracellular matrix (ECM) protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes.,Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin.,ECM protein deposition was measured at both subepithelial, and ASM layers.,The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects.,An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity.,A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls.,These findings indicate that airway remodeling also affects the large airways in COPD patients who have greater deposition of ECM proteins in the subepithelial layer and a larger smooth muscle area than control smoker subjects.,These changes may contribute to chronic airflow obstruction in COPD patients. | 1 |
Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke and characterized by chronic inflammation, alveolar destruction (emphysema) and bronchiolar obstruction.,Ozone is a gaseous constituent of urban air pollution resulting from photochemical interaction of air pollutants such as nitrogen oxide and organic compounds.,While acute exposure to ozone induces airway hyperreactivity and neutrophilic inflammation, chronic ozone exposure in mice causes activation of oxidative pathways resulting in cell death and a chronic bronchial inflammation with emphysema, mimicking cigarette smoke-induced COPD.,Therefore, the chronic exposure to ozone has become a model for studying COPD.,We review recent data on mechanisms of ozone induced lung disease focusing on pathways causing chronic respiratory epithelial cell injury, cell death, alveolar destruction, and tissue remodeling associated with the development of chronic inflammation and AHR.,The initial oxidant insult may result from direct effects on the integrity of membranes and organelles of exposed epithelial cells in the airways causing a stress response with the release of mitochondrial reactive oxygen species (ROS), DNA, and proteases.,Mitochondrial ROS and mitochondrial DNA activate NLRP3 inflammasome and the DNA sensors cGAS and STING accelerating cell death pathways including caspases with inflammation enhancing alveolar septa destruction, remodeling, and fibrosis.,Inhibitors of mitochondrial ROS, NLRP3 inflammasome, DNA sensor, cell death pathways, and IL-1 represent novel therapeutic targets for chronic airways diseases underlined by oxidative stress. | Cigarette smoke (CS) exposure is the leading risk factor for COPD-emphysema pathogenesis.,A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity.,However, the underlying mechanism is unclear.,Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells) and Pseudomonas aeruginosa (PA01-GFP) as an experimental model.,Briefly, RAW cells were treated with cigarette smoke extract (CSE), chloroquine (autophagy inhibitor), TFEB-shRNA, CFTR(inh)-172, and/or fisetin prior to bacterial infection for functional analysis.,Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p < 0.01), autophagy inhibition (p < 0.05; p < 0.01), TFEB knockdown (p < 0.01; p < 0.001), and inhibition of CFTR function (p < 0.001; p < 0.01) in comparison to the control group(s) that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p < 0.05; p < 0.01; and p < 0.001).,Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p < 0.01; p < 0.001), which warrants further investigation.,Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis. | 1 |
To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.,Systematic searches MEDLINE and Embase based on predetermined criteria.,Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortality and adverse events.,Qualitative comparisons of efficacies between RCTs and observational studies.,212 RCTs and 19 observational studies were included.,Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)).,No differences in lung function (0.02 (95% CI: −0.10 to 0.14)), health-related quality of life (−1.12 (95% CI: −3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found.,Most of the observational evidence trended in the same direction as pooled RCT data.,Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits.,CRD42018088013. | An extrafine formulation of the long-acting muscarinic antagonist glycopyrronium bromide (GB) is in development for chronic obstructive pulmonary disease (COPD), in combination with beclometasone dipropionate and formoterol fumarate - a “fixed triple”.,This two-part study was randomized, double blind, placebo controlled in patients with moderate-to-severe COPD: Part 1: single-dose escalation, GB 12.5, 25, 50, 100 or 200 μg versus placebo; Part 2: repeat-dose (7-day), four-period crossover, GB 12.5, 25 or 50 μg twice daily (BID) versus placebo, with an open-label extension in which all patients received tiotropium 18 μg once daily.,On the morning of Day 8 in all five periods, patients also received formoterol 12 μg.,In study Part 1, 27 patients were recruited.,All GB doses significantly increased from baseline forced expiratory volume in 1 second (FEV1) area under the curve (AUC0-12h) and peak FEV1, with a trend toward greater efficacy with higher GB dose.,All adverse events were mild-moderate in severity, with a lower incidence with GB than placebo and no evidence of a dose-response relationship.,In study Part 2, of 38 patients recruited, 34 completed the study.,Adjusted mean differences from placebo in 12 h trough FEV1 on Day 7 (primary) were 115, 142 and 136 mL for GB 12.5, 25 and 50 μg BID, respectively (all P<0.001).,GB 25 and 50 μg BID were superior (P<0.05) to GB 12.5 μg BID for pre-dose morning FEV1 on Day 8.,For this endpoint, GB 25 and 50 μg BID were also superior to tiotropium.,Compared with Day 7, addition of formoterol significantly increased Day 8 FEV1 peak and AUC0-12h with all GB doses and placebo (all P<0.001).,All adverse events were mild-moderate in severity and there was no indication of a dose-related relationship.,This study provides initial evidence on bronchodilation, safety and pharmacokinetics of extrafine GB BID.,Overall, the results suggest that GB 25 μg BID is the optimal dose in patients with COPD. | 1 |
This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study.,Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information.,Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD.,Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients.,Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire.,Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description.,The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years.,Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study.,Participants’ daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues.,66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids).,Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL.,In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants’ daily functioning, activities and self-care.,The findings provided significant additional knowledge to the SLS COPD study findings.,Interviews with patients undergoing a clinical trial for chronic lung disease highlights the impact of breathlessness on quality of life.,Henrik Svedsater at GlaxoSmithKline in the UK, and co-workers, wanted to dig deeper into patient perceptions of COPD during the Salford Lung Study in Chronic Obstructive Pulmonary Disease (SLS COPD) clinical trial, which trialed an alternative self-administered inhaler treatment.,To this end, Svedsater’s team administered questionnaires and interviewed 400 patients involved in SLS COPD, to examine disease impacts on their quality of life.,The patients cited breathlessness as having the greatest bearing on daily life, particularly on their ability to carry out physical tasks and continue a self-care regime.,Investigations of disease impact should be incorporated into future clinical trials, particularly to assess how improving lung function affects patient perceptions and quality of life. | Patients with COPD on long term oxygen therapy frequently do not adhere to their prescription, and they frequently do not use their ambulatory oxygen systems as intended.,Reasons for this lack of adherence are not known.,The aim of this study was to obtain in-depth information about perceptions and use of prescribed ambulatory oxygen systems from patients with COPD to inform ambulatory oxygen design, prescription and management.,A qualitative design was used, involving semi-structured face-to-face interviews informed by a grounded theory approach.,Twenty-seven UK community-dwelling COPD patients using NHS prescribed ambulatory systems were recruited.,Ambulatory oxygen systems comprised cylinders weighing 3.4 kg, a shoulder bag and nasal cannulae.,Participants reported that they: received no instruction on how to use ambulatory oxygen; were uncertain of the benefits; were afraid the system would run out while they were using it (due to lack of confidence in the cylinder gauge); were embarrassed at being seen with the system in public; and were unable to carry the system because of the cylinder weight.,The essential role of carers was also highlighted, as participants with no immediate carers did not use ambulatory oxygen outside the house.,These participants highlighted previously unreported problems that prevented them from using ambulatory oxygen as prescribed.,Our novel findings point to: concerns with the lack of specific information provision; the perceived unreliability of the oxygen system; important carer issues surrounding managing and using ambulatory oxygen equipment.,All of these issues, as well as previously reported problems with system weight and patient embarrassment, should be addressed to improve adherence to ambulatory oxygen prescription and enhance the physical and social benefits of maintaining mobility in this patient group.,Increased user involvement in both system development and service provision planning, could have avoided many of the difficulties highlighted by this study. | 1 |
Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease.,In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators.,Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease.,The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use.,We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies.,Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.,A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease.,Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD).,While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs).,Anthony D’Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials.,Of these, 1180 were already taking ICSs.,The team compared symptoms in the ICS group with those not taking ICSs.,The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity. | 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. | 1 |
To characterise patients with chronic obstructive pulmonary disease (COPD) who are rehospitalised for an acute exacerbation, to estimate the cost of these hospitalisations, to characterise high risk patient sub groups and to identify factors potentially associated with the risk of rehospitalisation.,This was a retrospective study using the French National Hospital Discharge Database.,All patients aged ≥40 years hospitalised for an acute exacerbation of COPD between 2015 and 2016 were identified and followed for six months.,Patients with at least one rehospitalisation for acute exacerbation of COPD constituted the rehospitalisation analysis population.,A machine learning model was built to study the factors associated with the risk of rehospitalisation using decision tree analysis.,A direct cost analysis was performed from the perspective of national health insurance.,A total of 143,006 eligible patients were hospitalised for an acute exacerbation of COPD (AECOPD) in 2015-2016 (mean age: 74 years; 62.1% men).,25,090 (18.8%) were rehospitalised for another exacerbation within six months.,In this study, 8.5% of patients died during or immediately following the index hospitalisation and 10.5% died during or immediately after rehospitalisation (p <0.001).,The specific cost of these rehospitalisations was € 5304.,The overall total cost per patient of all AECOPD-related stays was € 9623, being significantly higher in patients who were rehospitalised (€ 16,275) compared to those who were not (€ 8208).,In decision tree analysis, the most important driver of rehospitalisation was hospitalisation in the previous two years (contributing 85% of the information).,Rehospitalisations for acute exacerbations of COPD carry a high epidemiological and economic burden.,Since hospitalisation for an acute exacerbation is the most important determinant of future rehospitalisations, management of COPD needs to focus on interventions aimed at decreasing the rehospitalisation risk of in order to lower the burden of disease. | 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 |
Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD).,The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD.,It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD.,Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded.,The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded.,Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (19±6 vs. 13±4 seconds, respectively; p = 0.001).,The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group.,In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups.,Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control.,These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD. | Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD).,However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD.,The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness.,Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision.,Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control.,Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037).,Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047), decreased anterior body sway during back muscle vibration (p = 0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002).,Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037).,Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls.,These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability.,Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. | Although timely treatment of COPD exacerbations seems clinically important, nearly half of these exacerbations remain unreported and subsequently untreated.,Recent studies have investigated incidence and impact of failure to seek medical treatment during exacerbations.,Yet, little is known about type and timing of other self-management actions in periods of symptom deterioration.,The current prospective study aims at determining the relative incidence, timing and determinants of three types of patient responses.,In a multicentre observational study, 121 patients (age 67 ± 11 years, FEV1pred. 48 ± 19) were followed for 6 weeks by daily diary symptom recording.,Three types of action were assessed daily: planning periods of rest, breathing techniques and/or sputum clearing (type-A), increased bronchodilator use (type-B) and contacting a healthcare provider (type-C).,Type-A action was taken in 70.7%, type-B in 62.7% and type C in 17.3% of exacerbations (n = 75).,Smokers were less likely to take type-A and B actions.,Type-C actions were associated with more severe airflow limitation and increased number of hospital admissions in the last year.,Our study shows that most patients are willing to take timely self-management actions during exacerbations.,Future research is needed to determine whether the low incidence of contacting a healthcare provider is due to a lack of self-management or healthcare accessibility. | 1 |
Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined.,Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed‐up for 1 year.,Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage.,Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation.,Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation.,The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A.,The Kaplan‐Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively.,The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation. | The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations.,The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations.,However, the clinical characteristics and outcomes in these patients are not well documented.,In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry.,All patients with stable COPD were classified into the four groups defined by GOLD 2017.,The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.,Four hundred and one patients with stable COPD were identified.,There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D.,Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A.,Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period.,Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B).,Mortality was not different between the high-risk and low-risk groups.,The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality. | 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. | The objective of this study was to measure health-related quality of life (HRQL) in outpatients with chronic obstructive pulmonary disease (COPD) and to assess differences in HRQL according to age, gender, and severity of COPD.,A total of 9405 patients (79% men, mean age 68 years) participated in a cross-sectional study.,HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12).,Severity of COPD was graded into three levels according to forced expiratory volume in one second value.,COPD severity was mild in 33.8% of cases, moderate in 49.3% and severe in 16.8%.,The mean physical component summary (PCS-12) and mental component summary (MCS-12) scores were 36.8 ± 10.4 and 47.2 ± 11.2, respectively.,General health and physical functioning domains were those with the lowest scores.,The mean MCS-12 scores were significantly higher in men (47.9 ± 10.9) than in women (44.1 ± 11.8) (P < 0.001).,Patients older than 60 years rated HRQL worse than patients aged 40-59 years.,There were statistically significant differences according to severity of disease in the mean scores of all domains of the PCS-12 and MCS-12 scales.,The present findings show the influence of female gender, older age and moderate-to-severe of airflow limitation on HRQL in outpatients with COPD attended in daily practice. | 1 |
COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation.,Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease.,We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response.,Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<− 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10).,At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR.,122 subjects were included in this analysis.,Emphysema and small airways disease had independent associations with airflow obstruction (β = − 0.34, p < 0.001 and β = − 0.56, p < 0.001).,%LAA<− 950 had independent associations with gas transfer (β = − 0.37, p < 0.001) and E/I MLD with RV/TLC (β = 0.30, p =0.003).,The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (β = 0.73, p < 0.001).,Pi10 did not show any independent associations with lung function or functional parameters.,No CT parameters had any associations with sputum inflammatory cells.,Greater emphysema was associated with lower levels of systemic inflammation (CRP β = − 0.34, p < 0.001 and fibrinogen β = − 0.28, p =0.003).,There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not.,This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status.,In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.,The online version of this article (10.1186/s12931-018-0734-y) contains supplementary material, which is available to authorized users. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
Telerehabilitation (TR) aimed at patients with COPD has shown promising effects on symptoms, physical function, and quality of life, but little research has been conducted to understand the impact of implementation on frontline health professionals.,Therefore, the aim of this study was to examine the barriers and enablers of health professionals to online exercise-based TR in patients with COPD, to support a successful implementation process.,Semistructured individual and focus group interviews were conducted with 25 health professionals working with conventional COPD rehabilitation or TR.,Interviews were audio-taped and transcribed verbatim.,Investigator triangulation was applied during data generation.,The Theoretical Domains Framework directed the interview guide and was used as a coding framework in the analysis.,We identified six predominant domains essential in understanding the enablers and barriers of TR from a staff perspective: 1) skills, 2) professional role and identity, 3) beliefs about capabilities, 4) beliefs about consequences, 5) environmental context and resources, and 6) social influences.,We found that health professionals held both enablers and barriers important for the implementation process of TR.,TR introduces new work tasks and new ways for the health professionals to communicate and exercise with the patients, which influence their professional role and self-perceived capability.,Specific attention toward involvement of the health professionals in the decision process combined with sufficient education and skill training is highly essential to support a successful implementation of TR in clinical practice. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence.,Its underdiagnosis and hence under-treatment is a general feature across all countries.,This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease.,A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms.,Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted.,In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”.,In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation.,Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy.,This is an essential issue in COPD.,In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease.,Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”.,To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation.,The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD.,Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both. | 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 |
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow.,The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression.,Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs.,Among these new drugs, we focussed on thioredoxin (Trx).,Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways.,The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses.,In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF).,Taken together, these findings suggest that Trx may be the ideal drug for treating COPD. | To describe the temporal and spatial trends of mortality and disability adjusted life years (DALYs) due to chronic respiratory diseases, by age and sex, across the world during 1990-2017 using data from the Global Burden of Disease Study 2017.,Systematic analysis.,The Global Burden of Diseases, Injuries, and Risk Factors Study 2017.,Mortality and DALYs from chronic respiratory diseases were estimated from the Global Burden of Disease Study 2017 using DisMod-MR 2.1, a Bayesian meta-regression tool.,The estimated annual percentage change of the age standardised mortality rate was calculated using a generalised linear model with a Gaussian distribution.,Mortality and DALYs were stratified according to the Socio-demographic index.,The strength and direction of the association between the Socio-demographic index and mortality rate were measured using the Spearman rank order correlation.,Risk factors for chronic respiratory diseases were analysed from exposure data.,Between 1990 and 2017, the total number of deaths due to chronic respiratorydiseases increased by 18.0%, from 3.32 (95% uncertainty interval 3.01 to 3.43) million in 1990 to 3.91 (3.79 to 4.04) million in 2017.,The age standardised mortality rate of chronic respiratory diseases decreased by an average of 2.41% (2.28% to 2.55%) annually.,During the 27 years, the annual decline in mortality rates of chronic obstructive pulmonary disease (COPD; 2.36%, uncertainty interval 2.21% to 2.50%) and pneumoconiosis (2.56%, 2.44% to 2.68%) has been slow, whereas the mortality rate for interstitial lung disease and pulmonary sarcoidosis (0.97%, 0.92% to 1.03%) has increased.,Reductions in DALYs for asthma and pneumoconiosis have been seen, but DALYs due to COPD, and interstitial lung disease and pulmonary sarcoidosis have increased.,Mortality and the annual change in mortality rate due to chronic respiratory diseases varied considerably across 195 countries.,Assessment of the factors responsible for regional variations in mortality and DALYs and the unequal distribution of improvements during the 27 years showed negative correlations between the Socio-demographic index and the mortality rates of COPD, pneumoconiosis, and asthma.,Regions with a low Socio-demographic index had the highest mortality and DALYs.,Smoking remained the major risk factor for mortality due to COPD and asthma.,Pollution from particulate matter was the major contributor to deaths from COPD in regions with a low Socio-demographic index.,Since 2013, a high body mass index has become the principal risk factor for asthma.,Regions with a low Socio-demographic index had the greatest burden of disease.,The estimated contribution of risk factors (such as smoking, environmental pollution, and a high body mass index) to mortality and DALYs supports the need for urgent efforts to reduce exposure to them. | 1 |
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. | The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.,We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation.,Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.,We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation.,In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB).,After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40-0.64) and ACE inhibitor/ARB use (0.55, 0.46-0.66) were significantly associated with decreased 90-day mortality.,Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation.,Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. | 1 |
Pulmonary surfactant D (SP-D) has important regulatory functions for innate immunity and has been implicated as a biomarker for chronic obstructive pulmonary disease (COPD).,We hypothesized that COPD patients would have reduced bronchoalveolar lavage (BAL) fluid SP-D levels compared to healthy smoking and non-smoking controls.,BAL SP-D and phospholipids were quantified and corrected for dilution in 110 subjects (65 healthy never smokers, 23 smokers with normal spirometry, and 22 smokers with COPD).,BAL SP-D was highest in never smokers (mean 51.9 μg/mL ± 7.1 μg/mL standard error) compared to both smokers with normal spirometry (16.0 μg/mL ± 11.8 μg/mL) and subjects with COPD (19.1 μg/mL ± 12.9 μg/mL; P < 0.0001).,Among smokers with COPD, BAL SP-D correlated significantly with FEV1% predicted (R = 0.43; P < 0.05); however, the strongest predictor of BAL SP-D was smoking status.,BAL SP-D levels were lowest in current smokers (12.8 μg/mL ± 11.0 μg/mL), intermediate in former smokers (25.2 μg/mL ± 14.2 μg/mL; P < 0.008), and highest in never smokers.,BAL phospholipids were also lowest in current smokers (6.5 nmol ± 1.5 nmol), intermediate in former smokers (13.1 nmol ± 2.1 nmol), and highest in never smokers (14.8 nmol ± 1.1 nmol; P < 0.0001).,These data suggest that smokers, and especially current smokers, exhibit significantly reduced BAL SP-D and phospholipids compared to nonsmokers.,Our findings may help better explain the mechanism that leads to the rapid progression of disease and increased incidence of infection in smokers. | There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD).,The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.,We studied 23 patients with advanced COPD.,Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.,At baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549).,Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status.,The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018).,Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.,Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD.,These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients. | 1 |
Exacerbations are critical events in chronic pulmonary obstructive disease (COPD).,The frequency of COPD exacerbations is associated with the prognosis, including mortality, but no useful biomarker has been established.,The present retrospective study investigated 481 COPD patients.,Clinical features in the stable period were compared between patients who experienced severe exacerbation (n = 88, 18.3%) and those who never experienced severe exacerbation (n = 393, 81.7%).,In the patients who experienced exacerbations, clinical features were also compared between frequent exacerbators (exacerbation rate ≥ 2 times/year, n = 27, 30.7%) and infrequent exacerbators (1 time/year, n = 61, 69.3%).,Compared to COPD patients who never experienced exacerbations, body mass index (BMI), serum albumin, and pulmonary functions were significantly lower, and the cardiovascular disease comorbidity rate, COPD assessment test score, modified Medical Research Council dyspnea scale, and use of long-term oxygen therapy, long-acting β2 adrenergic agonist therapy, inhaled corticosteroid therapy, and macrolide therapy were significantly higher in COPD patients with exacerbations (all p < 0.01).,In patients who experienced exacerbations, frequent exacerbators had significantly lower % forced expiratory volume in 1.0 s and a higher risk of critical exacerbations, percentage of blood eosinophils, history of mechanical ventilation use, and use of long-term oxygen therapy and of macrolide therapy than infrequent exacerbators (all p < 0.01).,On multivariate analysis, the percentage of blood eosinophils was the parameter most correlated with exacerbation frequency (β value [95% confidence interval] 1.45 [1.12-1.88], p < 0.01).,Blood eosinophil in the stable period is the factor most correlated with the frequency of severe exacerbations.,Trial registration: The patients in this study was registered retrospectively | Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide.,Patients with COPD frequently have systemic comorbidities that often require unscheduled hospitalization for exacerbation and deterioration of physical conditions, and can have a poor prognosis.,We verified factors affecting patients’ short-term mortality, using a national inpatient database in Japan.,We retrospectively collected data for COPD patients (age: >40 years) with emergency admission between July 2010 and March 2013, using the Diagnosis Procedure Combination database.,We performed multivariate logistic analyses fitted with a generalized estimating equation to assess factors associated with all-cause in-hospital mortality.,A total of 177,207 patients (mean age: 77.5 years; males: 72.9%) were identified.,All-cause in-hospital death occurred in 23,614 patients (13.7%).,Higher mortality was associated with older age, male sex, lower body mass index, more severe dyspnea, lower level of consciousness, and worse activities of daily life.,Higher mortality was also associated with comorbid conditions, including bacterial pneumonia, aspiration pneumonia, interstitial pneumonitis, pulmonary embolism, respiratory failure, lung cancer, heart failure, cerebral infarction, liver cirrhosis, and chronic renal failure.,Our study demonstrated that all-cause in-hospital mortality in patients with COPD who required emergency hospitalization was associated with deteriorated general conditions and comorbidities at admission.,Physicians should take into account these prognostic factors to choose better treatment options for COPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) is a public health problem.,Interprofessional collaboration and health promotion interventions such as exercise training, education, and behaviour change are cost effective, have a good effect on health status, and are recommended in COPD treatment guidelines.,There is a gap between the guidelines and the healthcare available to people with COPD.,The aim of this study was to increase the understanding of what shapes the provision of primary care services to people with COPD and what healthcare is offered to them from the perspective of healthcare professionals and managers.,The study was conducted in primary care in a Swedish county council during January to June 2015.,A qualitatively driven mixed methods design was applied.,Qualitative and quantitative findings were merged into a joint analysis.,Interviews for the qualitative component were performed with healthcare professionals (n = 14) from two primary care centres and analysed with qualitative content analysis.,Two questionnaires were used for the quantitative component; one was answered by senior managers or COPD nurses at primary care centres (n = 26) in the county council and the other was answered by healthcare professionals (n = 18) at two primary care centres.,The questionnaire data were analysed with descriptive statistics.,The analysis gave rise to the overarching theme building COPD care on shaky ground.,This represents professionals driven to build a supportive COPD care on ‘shaky’ organisational ground in a fragmented and non-compliant healthcare organisation.,The shaky ground is further represented by uninformed patients with a complex disease, which is surrounded with shame.,The professionals are autonomous and pragmatic, used to taking responsibility for their work, and with limited involvement of the management.,They wish to provide high quality COPD care with interprofessional collaboration, but they lack competence and are hindered by inadequate routines and lack of resources.,There is a gap between COPD treatment guidelines and the healthcare that is provided in primary care.,To facilitate implementation of the guidelines several actions are needed, such as further training for professionals, additional resources, and improved organisational structure for interprofessional collaboration and patient education.,The online version of this article (doi:10.1186/s12913-017-2393-y) contains supplementary material, which is available to authorized users. | In light of the growing burden of COPD, there is increasing focus on the role of self-management for this population.,Currently, self-management varies widely.,Little is known either about nurses’ and allied health professionals’ (AHPs’) understanding and provision of self-management in clinical practice.,This study explores nurses’ and AHPs’ understanding and implementation of supported COPD self-management within routine clinical practice.,Nurses and AHPs participated in face-to-face semistructured interviews to explore their understanding and provision of COPD self-management, as well as their perceptions of the challenges to providing such care.,Purposive sampling was used to select participants from a range of professions working within primary, community, and secondary care settings.,Three researchers independently analyzed each transcript using a thematic approach.,A total of 14 participants were interviewed.,Nurses and AHPs viewed self-management as an important aspect of COPD care, but often misunderstood what it involved, leading to variation in practice.,A number of challenges to supporting self-management were identified, which related to lack of time, lack of insight regarding training needs, and assumptions regarding patients’ perceived self-management abilities.,Nurses and AHPs delivering self-management require clear guidance, training in the use of effective self-management skills, and education that challenges their preconceptions regarding patients.,The design of health care services also needs to consider the practical barriers to COPD self-management support for the implementation of such interventions to be successful. | 1 |
Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors.,This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy.,Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2×2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2).,Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL).,A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors).,The primary endpoint was the proportion of patients making ≥1 critical error after reading the PIL.,The secondary endpoints included error rates during ≤2 reassessments following investigator instruction (if required), instruction time, and patient preference.,After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P<0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P<0.001).,The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P<0.001 for each substudy).,The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively).,Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively).,Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination. | The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD).,This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population.,This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study.,Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 μg (via ELLIPTA® dry powder inhaler) or PBO for 12 weeks.,The primary endpoint was St George’s Respiratory Questionnaire (SGRQ) total score at day 84.,Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1-12 and trough forced expiratory volume in 1 second on day 84.,Adverse events were also assessed.,A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups.,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: −4.03 [95% confidence interval {CI}: −6.28, −1.79]; P<0.001).,UMEC/VI 62.5/25 μg resulted in a statistically significant reduction in rescue albuterol use versus PBO (−0.7 puffs/day [95% CI: −1.1, −0.4]; P<0.001).,UMEC/VI 62.5/25 μg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001).,The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 μg and PBO groups, respectively).,The results of this study demonstrate that treatment with UMEC/VI 62.5/25 μg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD. | 1 |
We aim to assess if air pollution levels and climatological factors are associated with hospital admissions for exacerbation of chronic obstructive pulmonary disease (COPD) in Spain from 2004 to 2013.,We conducted a retrospective study.,Information on pollution level and climatological factors were obtained from the Spanish Meteorological Agency and hospitalizations from the Spanish hospital discharge database.,A case-crossover design was used to identify factors associated with hospitalizations and in hospital mortality.,Postal codes were used to assign climatic and pollutant factors to each patient.,We detected 162,338 hospital admissions for COPD exacerbation.,When seasonal effects were evaluated we observed that hospital admissions and mortality were more frequent in autumn and winter.,In addition, we found significant associations of temperature, humidity, ozone (O3), carbon monoxide (CO), particulate matter up to 10 μm in size (PM10) and nitrogen dioxide (NO2) with hospital admissions.,Lower temperatures at admission with COPD exacerbation versus 1, 1.5, 2 and 3 weeks prior to hospital admission for COPD exacerbation, were associated with a higher probability of dying in the hospital.,Other environmental factors that were related to in-hospital mortality were NO2, O3, PM10 and CO.,Epidemiology of hospital admissions by COPD exacerbation was negatively affected by colder climatological factors (seasonality and absolute temperature) and short-term exposure to major air pollution (NO2, O3, CO and PM10). | There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | 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. | Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone. | 1 |
Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | 1 |
This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients.,A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study.,The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay.,The correlations between their expression levels and clinical factors of patients were determined using linear regression methods.,The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history (P<0.05), but negatively correlated with the pulmonary function (P<0.05) of patients.,The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history (P<0.05), but positively correlated with the pulmonary function (P<0.05) of patients.,Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35.,The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD. | 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 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally.,Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments.,MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis.,Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC.,These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF).,Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD.,Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease.,Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion. | Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments.,In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression.,The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology.,The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription.,Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression).,However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling.,Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD.,Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression.,This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. | 1 |
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. | A subclinical left ventricle diastolic dysfunction (LVDD) has been described in patients with chronic obstructive pulmonary disease (COPD).,To evaluate the prevalence of LVDD in stable severe COPD patients, to analyze its relationship with exercise capacity and to look for its possible causes (lung hyperinflation, ventricular interdependence or inflammatory mechanisms).,We evaluated 106 consecutive outpatients with severe COPD (FEV1 between 30-50%).,Thirty-three (31%) were excluded because of previous heart disease.,A pulmonary function test, a 6-minute walking test (6MWT), a Doppler echocardiography test, including diastolic dysfunction parameters, and an analysis of arterial blood gases, NT-proBNP and serum inflammatory markers (CRP, leucocytes), were performed in all patients.,The prevalence of LVDD in severe stable COPD patients was 90% (80% type I, n=57, and 10% type II, n=7).,A significant association between a lower E/A ratio (higher LVDD type I) and a lower exercise tolerance (6-minute walked distance (6MWD)) was found (r=0.29, p<0.05).,The fully adjusted multivariable linear regression model demonstrated that a lower E/A ratio, a DLCO in the quartile 4th and a higher tobacco consumption were associated with a lower 6MWD (76, 57 and 0.7 metres, respectively, p<0.05).,A significant correlation between E/A ratio and PaO2 was observed (r=0.26, p<0.05), but not with static lung hyperinflation, inflammation or right ventricle overload parameters.,In stable severe COPD patients, the prevalence of LVDD is high and this condition might contribute in their lower exercise tolerance.,Hypoxemia could have a concomitant role in their pathogenesis. | 1 |
Although, to our knowledge, there has been no exhaustive or credible review of the evidence of the disease burden of COPD in China, COPD has become an increasing public health concern to the Chinese medical community.,The purpose of this article is to review the evidence and evaluate and clarify the disease burden of COPD in China with the aim of improving effective management.,We reviewed previous studies of COPD in China, which included data on prevalence, mortality, disease burden, risk factors, diagnosis, and management by searching related Web sites, including PubMed, ProQuest, and Thomson Reuters' Web of Knowledge, as well as major Chinese databases and government Web sites.,Reported COPD prevalence varied between 5% and 13% in different provinces/cities across China.,In 2008, COPD ranked fourth as a leading cause of death in urban areas and third in rural areas.,In addition, COPD accounted for 1.6% of all hospital admissions in China in that year.,The high prevalence of smoking and biomass fuel use acted as major contributors to the high occurrence of COPD in China.,Management of COPD in China should focus on adjusting the distribution of medical resources and on addressing public health policies to facilitate earlier diagnosis in rural areas, aim to reduce smoking prevalence, improve patients' self-management, and keep physicians' knowledge up to date and consistent with current guidelines.,COPD is one of the most challenging medical issues facing China because of its influence on both personal and public health and its impact on the economy.,Optimal management strategies should be adopted and strengthened immediately. | Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease.,Obesity with/without the metabolic syndrome and cachexia represent two poles of metabolic abnormalities that may relate to systemic inflammation.,On one hand systemic inflammatory syndrome likely reflects inflammation in the lungs, i.e. results from lung-to plasma spillover of inflammatory mediators.,On the other hand, obesity-related hypoxia results in local inflammatory response within adipose tissue per se, and may contribute to elevations in circulatory mediators by spillover from the adipose tissue to the systemic compartment.,The extent to which systemic hypoxia contributes to the adipose tissue inflammation remains unknown.,We assume that in patients with COPD and concurrent obesity at least three factors play a role in the systemic inflammatory syndrome: the severity of pulmonary impairment, the degree of obesity-related adipose tissue hypoxia, and the severity of systemic hypoxia due to reduced pulmonary functions.,The present review summarizes the epidemiological and clinical evidence linking COPD to obesity, the role of adipose tissue as an endocrine organ, and the role of hypoxia in adipose tissue inflammation. | 1 |
Previous studies have shown that progressive forms of non-alcoholic fatty liver disease (NAFLD) occur frequently in patients with obstructive lung disease (OLD).,However, few studies have written about this relationship.,This study aimed to investigate the relationship between OLD and NAFLD.,The Korea National Health and Nutrition Examination Survey is a national population-based, cross-sectional surveillance program that was initiated to assess the health and nutritional status of the Korean population.,From 2007 to 2010, 11,738 subjects were enrolled.,The subjects were defined as having NAFLD when they had scores higher than −0.640 in a NAFLD liver fat score prediction model, which was a previously validated prediction score.,Individuals with forced expiratory volume in one second/forced vital capacity <0.7 were considered to have OLD.,The subjects were divided into non-OLD and OLD groups and non-NAFLD and NAFLD groups.,All analyses were performed using sample weighting using the complex samples plan.,The prevalences of NAFLD and OLD were 30.2% and 8.9%, respectively.,Although not statistically significant, subjects in the NAFLD group involved a higher tendency of having OLD than did those in the non-NAFLD group (8.5% vs 10.0%, respectively, P=0.060).,Subjects with OLD showed a higher tendency to have NAFLD than non-OLD subjects (30.0% vs 33.7%, respectively, P=0.060).,NAFLD subjects were at higher odds of OLD (odds ratio=1.334; 95% confidence interval=1.108-1.607, P=0.002) than non-NAFLD subjects, after adjusting for age, sex, and smoking history.,OLD subjects were at higher odds of NAFLD (odds ratio=1.556; 95% confidence interval=1.288-1.879, P<0.001) than non-OLD subjects, after adjusting for age, sex, and smoking history.,This study showed that NAFLD is related to OLD.,Clinicians should be aware of possible liver comorbidities in OLD patients and that extrahepatic disease in NAFLD patients may vary more than previously thought. | Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients.,The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers.,In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment.,Proportional Cox regression analysis determined the best predictor of all cause survival.,During 83 months (±42), 43 patients died.,Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival.,In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03-1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35-5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality.,In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age. | 1 |
Given that physical activity (PA) has a positive impact on COPD symptoms and prognosis, this study examined the factors that both encourage and limit participation in PA for individuals with COPD in a primary care setting from the perspective of social cognitive theory.,A purposive sample of 26 individuals with a range of COPD severity (age range: 50-89 years; males =15) were recruited from primary care to participate in one of four focus groups.,Thematic analysis was undertaken to identify key concepts related to their self-efficacy beliefs.,Several barriers and enablers closely related to self-efficacy beliefs and symptom severity were identified.,The main barriers were health related (fatigue, mobility problems, breathing issues caused by the weather), psychological (embarrassment, fear, frustration/disappointment), attitudinal (feeling in control of their condition, PA perception, older age perception), and motivational.,The main enabling factors were related to motivation (autonomous or controlled), attitudes, self-regulation, and performance accomplishments.,When designing interventions for individuals with COPD, it is important to understand the patient-specific social cognitive influences on PA participation.,This information can then inform individually tailored management planning. | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
Findings from studies that examined the association between health-related quality of life (HRQOL) and smoking status among COPD patients have been mixed.,Moreover, factors associated with current smoking in COPD patients and differences by sex have not been fully elucidated.,Data from the 2011 and 2012 Behavioral Risk Factor Surveillance System was used in this study.,Four HRQOL indicators were examined in this study: general health, physical health, mental health, and activity limitations.,General health was dichotomized into two groups: “excellent/very good/good” and “fair/poor”, and the other three HRQOL indicators were dichotomized into <14 (infrequent) and ≥14 (frequent) unhealthy days in the past 30 days.,To examine HRQOL indicators in association with current versus former smoking and identify factors associated with current smoking, logistic regression models were used.,Sex differences were explored.,In COPD patients, current smokers compared to former smokers had significantly poor HRQOL on all subdomains: “fair/poor” general health (adjusted odds ratio [AOR]: 1.2 [95% confidence interval {CI}: 1.1-1.5]); poor physical health (AOR: 1.3 [CI: 1.1-1.5]); poor mental health (AOR: 1.8 [CI: 1.4-2.2]); and poor activity limitations (AOR: 1.5 [CI: 1.3-1.9]).,HRQOL subdomains affected by current smoking differed by sex except activity limitations.,General health (AOR: 1.5 [CI: 1.1-2.0]) and activity limitations (AOR: 1.6 [95% CI: 1.2-2.2]) in males and physical health (AOR: 1.3 [CI: 1.0-1.6]), mental health (AOR: 2.1 [CI: 1.7-2.6]), and activity limitations (AOR: 1.5 [CI: 1.2-1.9]) in females were significantly impaired due to current smoking.,Factors associated with current smoking differed by sex except being unmarried and having less than a college degree, which were associated with current smoking in both males and females.,These findings have important implications for health care providers in designing more effective interventions which tailor to and target specific subgroups for smoking cessation. | Numerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning.,Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population.,The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective.,Twenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them.,During the interview, the patients were asked to indicate in which way the selected domains impact their lives.,Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes.,The most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD.,We identified which domains of HRQoL are most important to patients with COPD.,One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD. | 1 |
Extracellular matrix (ECM) creates the tissue microenvironment and serves a role in airway wall remodeling in chronic obstructive pulmonary disease (COPD).,However, the biological function of ECM in COPD remains to be elucidated.,In the present study, 24 healthy Sprague Dawley rats were randomized to normal and COPD groups.,COPD was established by intratracheal injection with lipopolysaccharide over 30 days.,Subsequently, airway smooth muscle cells (ASMCs) were isolated from rats and served as a model to assess the effects of three ECM components, including collagen type I, laminin and collagen type III (COL-3).,Functional analysis in vitro, using cell counting kit-8, flow cytometry, wound healing and cell adhesion assays indicated that the ECM components could promote cell proliferation, cell cycle progression, migration and adhesion ability, respectively.,Furthermore, as demonstrated by ELISA, treatment with ECM components increased levels of C-X-C motif chemokine ligand 1 (CXCL1), CXCL8 and interleukin-6 in ASMCs.,Expression of transforming growth factor β1 (TGFβ1), fibroblast growth factor-1 (FGF-1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was increased, and expression of matrix metalloproteinase-9 (MMP-9) was decreased following treatment with ECM components, as demonstrated by reverse transcription-quantitative polymerase chain reaction and western blot analysis.,Additionally, specific activation of phosphoinositide 3-kinase (PI3K) signaling, using insulin-like growth factor-1 (IGF-1), promoted cell proliferation and cell cycle progression, increased expression of TGFβ1, FGF-1, PI3K, AKT, phospho-AKT, serine/threonine-protein kinase mTOR (mTOR), phospho-mTOR and TIMP1, promoted cell migration capacity and reduced the expression level of MMP-9 in cells from COPD rats.,Consistently, PI3K inhibitor LY294002 exerted the opposite effect to IGF-1.,In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway. | In this review we consider the therapeutic potential of targeting Akt for the treatment of COPD.,Akt is a serine/threonine protein kinase that functions as a signaling intermediate linked to multiple signaling programs involved in survival, inflammation, and growth.,Akt is closely associated with key membrane-bound receptors and represents a convergent integration point for multiple stimuli implicated in COPD pathogenesis.,Persistent activation of Akt secondary to somatic mutations in regulatory oncogenes, such as PTEN, may explain why inflammation in COPD does not resolve when smoking is ceased.,Akt is also implicated in the systemic manifestations of COPD such as skeletal muscle wasting and metabolic disturbances.,Furthermore, targeting Akt may provide a useful means of limiting the severity and duration of disease exacerbations in COPD.,As such, Akt represents a particularly attractive therapeutic target for the treatment of COPD.,Interestingly, current knowledge suggests that both inhibitors and activators of Akt may be useful for treating different clinical subpopulations of COPD patients. | 1 |
Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls.,Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown.,We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195).,BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency.,Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates.,BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers.,BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively.,Similar associations were not observed with plasma ferritin.,Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals. | There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients.,The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1).,Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors.,Systematic approaches were used to guide the analysis.,In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1.,Higher concentrations of potassium and sodium were associated with lower FEV1.,Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health.,In addition other novel associations found in this study merit further investigation. | 1 |
Guidelines recommendations for the treatment of COPD are poorly followed.,This could be related to the complexity of classification and treatment algorithms.,The purpose of this study was to validate a simpler dyspnea-based treatment algorithm for inhaled pharmacotherapy in stable COPD, comparing its concordance with the current Global Initiative for Obstructive Lung Disease (GOLD) guideline.,We enrolled patients who had been diagnosed with COPD in three primary care facilities and two tertiary hospitals in Spain.,We determined anthropometric data, forced expiratory volume in the 1st second (percent), exacerbations, and dyspnea based on the modified Medical Research Council scale.,We evaluated the new algorithm based on dyspnea and exacerbations and calculated the concordance with the current GOLD recommendations.,We enrolled 100 patients in primary care and 150 attending specialized care in a respiratory clinic.,There were differences in the sample distribution between cohorts with 41% vs 26% in grade A, 16% vs 12% in grade B, 16% vs 22% in grade C, and 27% vs 40% in grade D for primary and respiratory care, respectively (P=0.005).,The coincidence of the algorithm with the GOLD recommendations in primary care was 93% and 91.8% in the respiratory care cohort.,A simple dyspnea-based treatment algorithm for inhaled pharmacotherapy of COPD could be useful in the management of COPD patients and concurs very well with the recommended schema suggested by the GOLD initiative. | It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations.,The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations.,914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited.,Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients).,FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period.,816 patients (89.3%) concluded the study.,FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6.,We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6.,We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. | 1 |
The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities.,The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)?,An SR was performed using the Cochrane Collaboration protocol.,Nine electronic databases were searched up to July 2011.,Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham.,This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD.,Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance - 6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes.,Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes.,Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease.,The most common types of training were AT and RT.,BT and functional training were commonly applied in older adults.,The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores.,In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities.,A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training. | Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.,Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months.,Interviews were transcribed and analysed both thematically and as narratives.,Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.,Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.,Results Eleven patients died during the study period.,Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together).,Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.”,Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition.,Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease.,Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.,Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD.,The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care.,Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation. | 1 |
Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | Chronic obstructive pulmonary disease (COPD) is a debilitating condition characterized by airflow limitation that is not fully reversible.,It is a major cause of morbidity and mortality and represents substantial economic and social burden throughout the world.,A range of interventions has been developed that decrease symptoms and address complications associated with COPD.,However, to date few interventions have been unequivocally demonstrated to modify disease progression.,Assessment of the potential for interventions to modify disease progression is complicated by the lack of a clear definition of disease modification and disagreement over appropriate markers by which modification should be evaluated.,To clarify these issues, a working group of physicians and scientists from the USA, Canada and Europe was convened.,The proposed working definition of disease modification resulting from the group discussions was “an improvement in, or stabilization of, structural or functional parameters as a result of reduction in the rate of progression of these parameters which occurs whilst an intervention is applied and may persist even if the intervention is withdrawn”.,According to this definition, pharmacologic interventions may be considered disease-modifying if they provide consistent and sustained improvements in structural and functional parameters.,Smoking cessation and lung volume reduction surgery would both qualify as disease-modifying interventions. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) often have poor health-related quality of life (HRQoL) that is disproportionate to their degree of airflow limitation.,This study evaluated the association between St George’s Respiratory Questionnaire for COPD (SGRQ-C) score and forced expiratory volume in one second and investigated the factors responsible for high SGRQ-C score according to severity of airflow limitation.,Data from 1,264 COPD patients were obtained from the Korean COPD Subgroup Study (KOCOSS) cohort.,Patients were categorized into two groups according to severity of airflow limitation: mild-to-moderate and severe-to-very severe COPD groups.,We evaluated the clinical factors associated with high SGRQ-C score (≥25) in each COPD patient group.,Of the 1,264 COPD patients, 902 (71.4%) had mild-to-moderate airflow limitation and 362 (28.6%) had severe-to-very severe airflow limitation.,Of the mild-to-moderate COPD patients, 59.2% (534/902) had high SGRQ-C score, while 80.4% (291/362) of the severe-to-very severe COPD patients had high SGRQ-C score.,The association between SGRQ-C score and post-bronchodilator forced expiratory volume in one second (% predicted) was very weak in the mild-to-moderate COPD patients (r=−0.103, p=0.002) and weak in the severe-to-very severe COPD patients (r=−0.219, p<0.001).,Multiple logistic regression analysis revealed that age, being an ex- or current smoker, lower level of education, cough, dyspnea, and number of comorbidities with congestive heart failure, hyperlipidemia, and depression were significantly associated with high SGRQ-C score in mild-to-moderate COPD patients.,In comparison, being an ex-smoker and having respiratory symptoms including sputum and dyspnea were significant factors associated with high SGRQ-C score in severe-to-very severe COPD patients.,In addition to the respiratory symptoms of dyspnea and cough, high SGRQ-C score was associated with extra-pulmonary comorbidities in mild-to-moderate COPD patients.,However, only respiratory symptoms such as sputum and dyspnea were significantly associated with high SGRQ-C score in severe-to-very severe COPD patients.,This indicates the need for an improved management strategy for relieving respiratory symptoms in COPD patients with poor HRQoL.,In addition, attention should be paid to extra-pulmonary comorbidities, especially in mild-to-moderate COPD patients with poor HRQoL. | 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. | 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. | Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce.,This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.,Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male).,PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry.,Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.,PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05).,Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (TL,co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO2 peak) had significantly lower PA.,Multiple regression analysis identified 6 MWD and TL,co as independent predictors of PA in COPD.,The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD.,Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity. | 1 |
To determine the efficacy and usefulness of a chronic obstructive pulmonary disease (COPD) care bundle designed for the initial management of acute exacerbations of COPD and to assess whether it improves quality of care and provides better outcomes.,The level of care provided in the emergency department (ED) for COPD exacerbations varies greatly, and there is a need for a more systematic, consistent, evidence-based quality improvement approach to improve outcomes and costs.,A prospective before and after study was carried out in a university teaching hospital.,Fifty consecutive patients were identified in the ED with COPD exacerbations and their management was reviewed.,Following the education of ED staff and the implementation of a COPD care bundle, the outcome for 51 consecutive patients was analyzed.,This COPD care bundle consisted of ten elements considered essential to the management of COPD exacerbations and was scored 0-10 according to the number of items on the checklist implemented correctly.,Following implementation, the mean bundle score out of 10 improved from 4.6 to 7 (P<0.001).,There was a significant decrease in the unnecessary use of intravenous corticosteroids from 60% to 32% (P=0.003) and also a marked improvement in the use of oxygen therapy, with appropriate treatment increasing from 76% to 96% (P=0.003).,Prophylaxis for venous thromboembolism also improved from 54% to 73% (P=0.054).,The 30-day readmission rate did not significantly improve.,The use of a bundle improves the delivery of care for COPD exacerbations in the ED.,There is more appropriate use of therapeutic interventions, especially oxygen therapy and intravenous corticosteroids. | During our medical training, we learned that oxygen administration in patients with chronic obstructive pulmonary disease (COPD) induces hypercapnia through the 'hypoxic drive' mechanism and can be dangerous.,This mindset frequently results in the reluctance of clinicians to administer oxygen to hypoxemic patients with COPD.,However, this fear is not based on evidence in the literature.,Here, we will review the impact and pathophysiology of oxygen-induced hypercapnia in patients with acute exacerbation of COPD and recommend a titrated oxygen management. | 1 |
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. | 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 |
Alpha-1 antitrypsin deficiency (AATD) is a common hereditary disorder caused by mutations in the SERPINA1 gene, which encodes alpha-1 antitrypsin (AAT; also known as alpha 1-proteinase inhibitor, A1-PI).,An important function of A1-PI in the lung is to inhibit neutrophil elastase, one of various proteolytic enzymes released by activated neutrophils during inflammation.,Absence or deficiency of A1-PI leads to an imbalance between elastase and anti-elastase activity, which results in progressive, irreversible destruction of lung tissue, and ultimately the development of chronic obstructive pulmonary disease with early-onset emphysema.,AATD is under-diagnosed, patients can experience long delays before obtaining an accurate diagnosis, and the consequences of delayed diagnosis or misdiagnosis can be severe.,Currently, A1-PI therapy is the only available treatment that addresses disease etiology in patients with AATD; however, demonstrating clinical efficacy of A1-PI therapy is challenging.,In order to show therapeutic efficacy with traditional endpoints such as forced expiratory volume in one second and mortality, large sample sizes and longer duration trials are required.,However, AATD is a rare, slow progressive disease, which can take decades to manifest clinically and recruiting sufficient numbers of patients into prolonged placebo-controlled trials remains a significant obstacle.,Despite this, the Randomized, placebo-controlled trial of augmentation therapy in Alpha 1-Proteinase Inhibitor Deficiency (RAPID) and RAPID Extension trial, the largest clinical program completed to date, utilized quantitative chest computed tomography as a sensitive and specific measure of the extent of emphysema.,Findings from the RAPID/RAPID Extension program definitively confirmed the benefits of A1-PI therapy in slowing disease progression and provided evidence of a disease-modifying effect of A1-PI therapy in patients with AATD.,These findings suggest that the early introduction of treatment in patients with severe emphysema-related AATD may delay the time to death, lung transplantation or crippling respiratory complaints.,In addition, there is now limited evidence that A1-PI therapy provides a gain of more than five life-years, supporting previous observations based on registry data.,With the clinical efficacy of A1-PI therapy now demonstrated, further studies are required to assess long-term outcomes. | Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation.,Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment.,Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process.,Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions.,This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD. | 1 |
The extracellular matrix (ECM) of the lung plays several important roles in lung function, as it offers a low resistant pathway that allows the exchange of gases, provides compressive strength and elasticity that supports the fragile alveolar-capillary intersection, controls the binding of cells with growth factors and cell surface receptors and acts as a buffer against retention of water.,COPD is a chronic inflammatory respiratory condition, characterised by various conditions that result in progressive airflow limitation.,At any stage in the course of the disease, acute exacerbations of COPD may occur and lead to accelerated deterioration of pulmonary function.,A key factor of COPD is airway remodelling, which refers to the serious alterations of the ECM affecting airway wall thickness, resistance and elasticity.,Various studies have shown that serum biomarkers of ECM turnover are significantly associated with disease severity in patients with COPD and may serve as potential targets to control airway inflammation and remodelling in COPD.,Unravelling the complete molecular composition of the ECM in the diseased lungs will help to identify novel biomarkers for disease progression and therapy.,Airway remodelling in COPD refers to alterations of the lung ECM that affect airway wall thickness, resistance and elasticity.,Unravelling such molecular modifications will help us to identify novel biomarkers for disease progression and therapy.https://bit.ly/2LObAga | 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 |
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. | COPD is a progressive lung disorder with rates of mortality between 36-50%, within 2 years after admission for an acute exacerbation.,While treatment with inhaled bronchodilators and steroids may partially relieve symptoms and oxygen therapy may prolong life, for many patients the course of the disease is one of inexorable decline.,Very few palliative care intervention studies are available for this population.,This trial seeks to determine the effectiveness of the introduction of specialized palliative care on hospital, intensive care unit and emergency admissions of patients with severe and very severe COPD.,The study is a three year single centre, randomized controlled trial using a 2 arms parallel groups design conducted in a tertiary center (University Hospitals; Geneva).,For the intervention group, an early palliative care consultation is added to standard care; the control group benefits from standard care only.,Patients with COPD defined according to GOLD criteria with a stage III or IV disease and/or long term treatment with domiciliary oxygen and/or home mechanical ventilation and/or one or more hospital admissions in the previous year for an acute exacerbation are eligible to participate.,Allocation concealment is achieved using randomisation by sealed envelopes.,Our sample size of 90 patients/group gives the study a 80% power to detect a 20% decrease in intensive care unit and emergency admissions - the primary endpoint.,All data regarding participants will be analysed by a researcher blinded to treatment allocation, according to the "Intention to treat" principle.,Given the trends toward aggressive and costly care near end-of-life among patients with COPD, a timely introduction of palliative care may limit unnecessary and burdensome personal and societal costs, and invasive approaches.,The results of this study may provide directions for future palliative care interventions in this particular population.,This trial has been registered at clinicaltrials.gov underNCT02223780 | 1 |
To describe symptoms and lung function in patients registered with asthma or chronic obstructive pulmonary disease (COPD) in primary care and to examine how spirometry findings fit with general practitioners’ (GPs) diagnoses.,Patients aged ≥40 years with a diagnosis of asthma or COPD registered in the electronic medical record during the previous 5 years were recruited at seven GP offices in Norway in 2009-2010.,Registered diagnosis, spirometry results, comorbidity, and reported symptoms were compared.,Among 376 patients, 62% were women.,Based on Global Initiative for Chronic Obstructive Lung Diseases criteria, a spirometry diagnosis of COPD could be made in 68.1% of the patients with a previous COPD diagnosis and in 17.1% of those diagnosed with asthma only (P < 0.001).,The κ agreement between last clinical diagnosis of COPD and COPD based on spirometry was 0.50.,A restrictive spirometry pattern was found in 19.4% and more frequently in patients diagnosed with both asthma and COPD (23.9%) than in patients diagnosed with COPD only (6.8%, P = 0.003).,The ability of GPs to differentiate between asthma and COPD seems to have considerably improved during the last decade, probably due to the dissemination of spirometry and guidelines for COPD diagnosis.,A diagnosis of COPD that cannot be confirmed by spirometry represents a challenge in clinical practice, in particular when a restrictive pattern on spirometry is found. | The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764 | 1 |
The expression of HDAC2 is reported as reduced in chronic obstructive pulmonary disease (COPD).,We assessed HDAC2 expression within the airways of smokers and subjects with COPD and effects of inhaled corticosteroids (ICS), using immuno-histology to contrast with previous molecular methodology.,Endobronchial biopsies (ebb) from current smokers with COPD (COPD-CS; n = 15), ex-smokers with COPD (COPD-ES; n = 17), smokers with normal lung function (NS; n = 16) and normal controls (NC; n = 9) were immunostained for HDAC2.,A double-blinded, randomized, placebo-controlled 6 months intervention study assessed effects of ICS on HDAC2 in 34 COPD subjects.,There was no difference in epithelial HDAC2 staining in all groups.,There was a significant reduction in total cell numbers in the lamina propria (LP) in COPD-CS and NS (p<0.05).,LP cellularity correlated inversely with smoking history in COPD-CS (R = −0.8, p<0.003).,HDAC2 expression increased markedly in NS (p<0.001); in contrast COPD-CS was associated with suppressed signal (p<0.03), while normal in COPD-ES.,ICS did not affect HDAC2 cell staining.,Our findings suggest that airway HDAC2 expression is increased in the LP by smoking itself, but is reduced in COPD.,Ex-smokers have normalised HDAC2 cell expression, but ICS had no effect.,The paper emphasise the pit-falls of relying on molecular data alone to define airway changes.,Clinical Trial Registration Information:,The Australian New Zealand Clinical Trials Registry (ANZCTR),ACTRN12612001111864 | Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. | 1 |
Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD.,Fibroblast-derived WNT-5A inhibits canonical WNT-β-catenin-driven alveolar epithelial cell-mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.,Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide.,One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined.,Reduced WNT-β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated.,Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis.,We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens.,WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence.,Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro.,Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo.,Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin-driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD.,We thus identify a novel essential mechanism involved in impaired mesenchymal-epithelial cross talk in COPD pathogenesis, which is amenable to therapy. | Chronic obstructive pulmonary disease (COPD) is related to an abnormal chronic inflammatory response of the lung to mainly cigarette smoke (CS) and the disease risk is increased in aged individuals.,The source of this chronic inflammation is due to the repeated and progressive activation of immune cells.,We hypothesize that in a chronic CS-induced mouse model, the predisposition to COPD pathogenesis in aged mice is characterized by an elevated immune response compared to young animals.,We measured several characteristics of COPD in young and old mice (2 and 12 months of age) exposed to CS for 3 months.,CS-exposed aged mice exhibited increased lung compliance (0.061 ± 0.008 vs.,0.055 ± 0.006 ml/cm H2O, p < 0.01), emphysema development (35.36 ± 0.71 vs.,25.31 ± 0.005 μm; p < 0.01) and airway remodeling (2.15 ± 0.37 vs.,1.09 ± 0.64 μm3/μm2; p < 0.01) compared to control animals, which was not seen in CS-exposed young mice.,Quantification of lung tissue inflammation revealed a significantly greater volume of inducible bronchus-associated lymphoid tissue structures in aged mice after CS exposure (5.94 ± 2.89 vs.,2.37 ± 1.69 μm3/μm2; p < 0.01).,Our results indicate that age-induced lung inflammation is further elevated after CS exposure in old mice, potentially via an age-induced change in immune cell susceptibility to CS thereby accelerating the pathophysiological hallmarks of COPD. | 1 |
This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study.,COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 μg, 2.5 μg, 5 μg, 10 μg, or 20 μg Respimat® SMI (a novel, propellant-free device); tiotropium 18 μg HandiHaler®; placebo Respimat®; or placebo HandiHaler® for 3 weeks.,The primary endpoint was trough FEV1 on Day 21.,Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics.,In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo.,Tiotropium 5 μg Respimat®, 20 μg Respimat®, and tiotropium 18 μg HandiHaler® were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat® doses) versus 20 mL (placebo Respimat®); p < 0.05; and 230 mL (HandiHaler®) versus −90 mL (placebo HandiHaler®); p ≤ 0.001).,The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 μg Respimat® was comparable with tiotropium 18 μg HandiHaler®; the overall incidence of adverse events was comparable across treatment groups.,Tiotropium 5 and 10 μg Respimat® improve lung function in COPD patients and appear to be comparable with tiotropium 18 μg HandiHaler®. | 1 |
A thorough evaluation of the adequacy of clinical practice in a designated health care setting and temporal context is key for clinical care improvement.,This study aimed to perform a clinical audit of primary care to evaluate clinical care delivered to patients with COPD in routine clinical practice.,The Community Assessment of COPD Health Care (COACH) study was an observational, multicenter, nationwide, non-interventional, retrospective, clinical audit of randomly selected primary care centers in Spain.,Two different databases were built: the resources and organization database and the clinical database.,From January 1, 2015 to December 31, 2016 consecutive clinical cases of COPD in each participating primary care center (PCC) were audited.,For descriptive purposes, we collected data regarding the age at diagnosis of COPD and the age at audit, gender, the setting of the PCC (rural/urban), and comorbidities for each patient.,Two guidelines widely and uniformly used in Spain were carefully reviewed to establish a benchmark of adequacy for the audited cases.,Clinical performance was analyzed at the patient, center, and regional levels.,The degree of adequacy was categorized as excellent (> 80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (< 20%).,During the study 4307 cases from 63 primary care centers in 6 regions of the country were audited.,Most evaluated parameters were judged to fall in the inadequate performance category.,A correct diagnosis based on previous exposure plus spirometric obstruction was made in an average of 17.6% of cases, ranging from 9.8 to 23.3% depending on the region.,During the audited visit, only 67 (1.6%) patients had current post-bronchodilator obstructive spirometry; 184 (4.3%) patients had current post-bronchodilator obstructive spirometry during either the audited or initial diagnostic visit.,Evaluation of dyspnea was performed in 11.1% of cases.,Regarding treatment, 33.6% received no maintenance inhaled therapies (ranging from 31.3% in GOLD A to 7.0% in GOLD D).,The two most frequently registered items were exacerbations in the previous year (81.4%) and influenza vaccination (87.7%).,The results of this audit revealed a large variability in clinical performance across centers, which was not fully attributable to the severity of the disease. | Because additive effects of inhaled corticosteroids and long-acting anticholinergics are unclear, we undertook this study to compare the efficacy of tiotropium alone and tiotropium plus budesonide in patients with chronic obstructive pulmonary disease.,The study subjects were randomized to receive either tiotropium 18 µg once daily with or without budesonide 200 µg twice daily for 6 weeks.,The efficacy variables were changes in trough forced expiratory volume in one second (FEV1), St.,George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and use of rescue medication.,One hundred patients were randomized and 81 completed the study.,The mean age was 64.0 yr, and the mean FEV1 was 39.7% predicted.,Compared with tiotropium alone (N=40), the tiotropium/budesonide combination (N=41) was related to an improvement in the SGRQ total score (tiotropium -2.8 units and tiotropium/budesonide -5.6 units, p=0.003).,6MWD was improved by 13.5 m in the tiotropium group and by 22.5 m in the tiotropium/budesonide group (p=0.031).,Changes in trough FEV1 and the use of rescue medication were similar between two groups.,In conclusion, compared with tiotropium alone, the tiotropium/budesonide combination was related to an improved health-related quality of life.,These data support that low-dose budesonide may enhance the efficacy of tiotropium. | 1 |
Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | Several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment.,These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group.,This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD.,In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.,We used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD.,Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points.,Disease severity was using Forced Expiratory Volume in one second (FEV1); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index.,Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.,COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64).,Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases).,Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048).,Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001).,COPD is a major risk factor for cognitive impairment.,Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective.,Health care providers should consider screening their COPD patients for cognitive impairment. | 1 |
Early detection enables the possibility for interventions to reduce the future burden of COPD.,The Danish National Board of Health recommends that individuals >35 years with tobacco/occupational exposure, and at least 1 respiratory symptom should be offered a spirometry to facilitate early detection of COPD.,The aim, therefore, was to provide evidence for the feasibility and impact of doing spirometry in this target population.,Participating general practitioners (GPs) (n = 335; 10% of the Danish GPs) recruited consecutively, subjects with >35 years exposure, no previous diagnosis of obstructive lung disease, and at least 1 of the following symptoms: cough, dyspnea, wheezing, sputum, or recurrent respiratory infection.,Data on age, smoking status, pack-years, body mass index (BMI), dyspnea score (Medical Research Council, MRC), and pre-bronchodilator spirometry (FEV1, FEV1% predicted, FEV1/FVC) were obtained.,A total of 3.095 (51% females) subjects was included: mean age 58 years, BMI 26.3, and 31.5 pack-years.,The majority of subjects (88%) reported MRC score 1 or 2.,FEV1/FVC-ratio ≤ 0.7 was found in 34.8% of the subjects; the prevalence of airway obstruction increased with age and decreased with increasing BMI, and was higher in men and current smokers.,According to the level of FEV1, 79% of the subjects with airway obstruction had mild to moderate COPD.,More than one-third of the recruited subjects had airway obstruction (FEV1/ FVC < 0.7).,Early detection of COPD appears to be feasible through offering spirometry to adults with tobacco/occupational exposure and at least 1 respiratory symptom. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.,This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.,Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.,The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population.,The incidence of adverse events was also assessed.,In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population.,UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].,Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).,Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.,In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD.,Both treatments had similar safety profiles.,These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.,ClinicalTrials.gov identifier NCT02799784.,GlaxoSmithKline.,The online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users. | Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis.,We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD.,The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.,This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations.,Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.,In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%).,The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001).,In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%).,UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).,This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods.,UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy. | 1 |
Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals.,We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes.,By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs).,The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls.,Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2.,Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins.,The eQTLs for IREB2 and CHRNA5 were not in LD.,Seventy-four additional eQTL SNPs were associated with COPD at p<0.01.,These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6.,Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. | Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space.,However, mechanisms involved in its development are not fully understood.,Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated.,Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research.,Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema.,Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema.,This review also includes some reflections and suggestions on the research to come. | 1 |
The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg with twice-daily salmeterol/fluticasone (SFC) 50/500 μg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year.,This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up.,IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75-0.93), ≥2 exacerbations (RR: 0.85, 95% CI: 0.70-1.03) and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74-1.00).,Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history.,Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment.,IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67-0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70-0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80-1.22).,Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment.,The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone. | The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids.,However, this treatment has not been shown to reduce mortality and can potentially have serious side effects.,Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone.,By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.,This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark.,The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L.,The primary endpoint is length of hospital stay within 14 days after recruitment.,The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.,This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.,Clinicaltrials.gov, NCT02857842, 02-august-2016.,Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016. | 1 |
Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been studied in relation to the susceptibility to COPD and COPD with pulmonary hypertension (PH) with inconclusive results.,We performed the first comprehensive meta-analysis to evaluate accurately the association between the ACE gene polymorphism and the risk of COPD.,Data were analyzed using odds ratios (ORs) and the corresponding 95% CIs to measure the strength of the models.,Subgroup analyses were conducted by ethnicity and complication which referred to PH.,In total, 15 studies (2,635 participants) were included in our study, of which four studies (288 participants) were for PH subgroup.,The overall analysis results indicated that the ACE gene polymorphism was not associated with COPD susceptibility in all gene models.,However, the ethnic subgroup analysis results indicated that ACE gene polymorphism was associated with Asians’ susceptibility to COPD (DD+DI vs II, OR=1.47, P=0.019, 95% CI: 1.07-2.02).,Further, the overall results of the present study detected no statistical significance between ACE gene polymorphism and the risk of COPD with PH, but the homozygote variant (DD) increased the risk of PH in Asian COPD patients (DD vs ID+II, OR=2.05, P=0.05, 95% CI: 1.00-4.19).,The current study suggests that ACE polymorphism, particularly the homozygote variant (DD), might contribute to the risk of COPD and COPD with PH among Asians.,Further studies with larger sample size and more ethnicities are expected to be conducted in the future to validate the results. | Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI).,The impact of undiagnosed COPD in these patients is unknown.,We aimed to evaluate the prognostic impact of COPD - previously or newly diagnosed - in patients with IHD treated with PCI.,Patients with IHD confirmed by PCI were consecutively included.,After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors.,All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed.,A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included.,Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed.,IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction.,Median follow-up was 934 days (interquartile range [25%-75%]: 546-1,160).,COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76-44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04-3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12-2.83).,These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08-3.1).,Prevalence and underdiagnosis of COPD in patients with IHD who undergo PCI are both high.,These patients have an independent greater mortality and a higher number of cardiovascular events during follow-up. | 1 |
Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a devastating lung disease, mainly due to cigarette smoking, which represents the third cause of mortality worldwide.,The mechanisms driving its epithelial salient features remain largely elusive.,We aimed to evaluate the activation and the role of the canonical, β-catenin-dependant WNT pathway in the airway epithelium from COPD patients.,The WNT/β-catenin pathway was first assessed by WNT-targeted RNA sequencing of the air/liquid interface-reconstituted bronchial epithelium from COPD and control patients.,Airway expression of total and active β-catenin was assessed in lung sections, as well as WNT components in laser-microdissected airway epithelium.,Finally, we evaluated the role of WNT at the bronchial epithelial level by modulating the pathway in the reconstituted COPD epithelium.,We show that the WNT/β-catenin pathway is upregulated in the COPD airway epithelium as compared with that of non-smokers and control smokers, in targeted RNA-sequencing of in vitro reconstituted airway epithelium, and in situ in lung tissue and laser-microdissected epithelium.,Extrinsic activation of this pathway in COPD-derived airway epithelium inhibited epithelial differentiation, polarity and barrier function, and induced TGF-β-related epithelial-to-mesenchymal transition (EMT).,Conversely, canonical WNT inhibition increased ciliated cell numbers, epithelial polarity and barrier function, whilst inhibiting EMT, thus reversing COPD features.,In conclusion, the aberrant reactivation of the canonical WNT pathway in the adult airway epithelium recapitulates the diseased phenotype observed in COPD patients, suggesting that this pathway or its downstream effectors could represent a future therapeutic target.,This study was supported by the Fondation Mont-Godinne, the FNRS and the WELBIO. | Chronic obstructive pulmonary disease (COPD) is influenced by environmental and genetic factors.,An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys) α1-antitrypsin deficiency (AATD).,A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD.,Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy) and “normal” MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR.,A total of 162 genes were found to be differentially expressed (p-value ≤ 0.05 and |FC| ≥ 2) between MM and ZZ COPD patients.,Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue.,A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila) (SNAI1), and Krüppel-like transcription factors (KLFs) 4 (gut), 9 and 10, perfectly segregated ZZ and MM COPD patients.,The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis.,Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy.,These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD. | 1 |
Disease control is an important objective of COPD management.,The SINCON study evaluated the level of control in terms of respiratory symptoms and exacerbations in Spanish patients with COPD for ≥2 years.,SINCON was a descriptive, cross-sectional, multicenter study that assessed degree of control using a combined index comprising COPD assessment test (CAT), modified Medical Research Council dyspnea scale (mMRC), and number of moderate/severe exacerbations in the last year.,Based on this score, patients were categorized as “well controlled” or “poorly controlled”.,Degree of control was also assessed relative to patient phenotype, setting (primary care [PC] vs respiratory care [RC]), and impact of treatment on morning symptoms.,Of the 481 patients (PC: 307, RC: 174) analyzed, COPD was poorly controlled in 63.2%.,Some differences were found between clinical settings: PC patients were more poorly controlled (PC: 66.4% vs RC: 57.5%; P = 0.06) and had higher CAT score (PC: 17.9 vs RC: 15.5; P < 0.05), and higher rate of moderate/severe exacerbations during previous year (PC: 1.5 vs RC: 1.1; P < 0.05), while dyspnea degree was similar in both settings.,Regarding phenotypes, non-exacerbators demonstrated better control vs exacerbators.,Morning symptoms score improved between waking and 3 h after bronchodilator treatment (P < 0.05), with greater improvements in PC patients (PC: − 6.5 vs RC: − 5.0 points; P < 0.05).,Most COPD patients were poorly controlled with some differences observed between PC and RC settings and between patient phenotypes.,Our index may be easily used in PC settings to optimize COPD treatment. | Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear.,To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years’ follow-up or who died on treatment.,Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined.,We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes).,Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment.,Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history.,Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk. | 1 |
Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD.,Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations.,We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD.,This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals.,All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included.,The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters.,The main outcome was death or readmission during a 5-year follow-up.,The secondary outcome was death.,Survival analysis was performed (log-rank and Cox).,We identified a total of 359 patients (195 men and 164 women, average age 72 years).,During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD.,In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02-1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42-15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003-2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68-4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004-1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003-1.05; P=0.028) on admission were significantly associated with the primary outcome.,Age, cancer, and procalcitonin were significantly associated with the secondary outcome.,COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization.,Baseline pulmonary function remains the strongest predictor of mortality and new admission.,Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient.,Respiratory rate at admission appears to be the most prognostic clinical parameter.,A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission. | 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 |
The burden of chronic obstructive pulmonary disease (COPD) is high.,Health benefits can be gained in primary care by early detection and preventive measures.,To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings.,Practices were randomised on strategy and stratified on SES setting.,The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants.,In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test.,The main outcome measure was the rate of COPD diagnoses after screening.,More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%).,In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%).,Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.,The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices. | Respiratory diseases, namely asthma and chronic obstructive pulmonary disease (COPD), account for one-fourth of the patients at the primary health-care (PHC) facilities in Pakistan.,Standard care practices to manage these diseases are necessary to reduce the morbidity and mortality rate associated with non-communicable diseases in developing countries.,To develop and measure the effectiveness of operational guidelines and implementation materials, with sound scientific evidence, for expanding lung health care, especially asthma and COPD through PHC facilities already strengthened for tuberculosis (TB) care in Pakistan.,A cluster randomized controlled trial with two arms (intervention and control), with qualitative and costing study components, is being conducted in 34 clusters; 17 clusters per arm (428 asthma and 306 COPD patients), in three districts in Pakistan from October 2014 to December 2016.,The intervention consists of enhanced case management of asthma and COPD patients through strengthening of PHC facilities.,The main outcomes to be measured are asthma and COPD control among the registered cases at 6 months.,Cluster- and individual-level analyses will be done according to intention to treat.,Residual confounding will be addressed by multivariable logistic and linear regression models for asthma and COPD control, respectively.,The trial is registered with ISRCTN registry (ISRCTN 17409338).,Currently, only about 20% of the estimated prevalent asthma and COPD cases are being identified and reported through the respective PHC network.,Lung health care and prevention has not been effectively integrated into the core PHC package, although a very well-functioning TB program exists at the PHC level.,Inclusion of these diseases in the already existent TB program is expected to increase detection rates and care for asthma and COPD. | 1 |
To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors.,In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥40 years were generated by random digit dialling.,Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration.,COPD was defined as post-bronchodilator FEV1/FVC <0.70 (fixed ratio, FR) and as FEV1/FVC <5th percentile (lower limits of normal, LLN).,Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD.,I2 and Tau2 analyses were used to evaluate heterogeneity.,Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0-57.2)) had spirometry that satisfied ATS criteria.,The population prevalence of COPD was 16.2% (95% CI, 14.5-17.8) by FR and 11.2% (95% CI, 9.7-12.6) by LLN.,Male predominance in prevalence was shown by FR but not by LLN criteria.,Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33-1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42-4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17-2.80).,In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55-4.80).,Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau2 analyses.,Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease.,This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD. | It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD).,We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use.,We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno.,We defined COPD as a post-bronchodilator FEV1/FVC < 70%.,Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001).,Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%).,Rather, we found that PARs of COPD varied by setting.,In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively).,In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%.,The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking.,This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas. | 1 |
The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant.,Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID.,This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St.,George’s Respiratory Questionnaire (SGRQ).,Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR).,CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months.,A 15-point Global Rating of Change scale (GRC) was completed at each follow-up.,A five-point GRC was used as second anchor at 12 months.,Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID.,The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency.,In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up.,Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ).,MCID estimates for improvement ranged − 3.1 to − 1.4 for CAT, − 0.6 to − 0.3 for CCQ, and − 10.3 to − 7.6 for SGRQ.,Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR.,Significantly absolute lower MCID estimates were observed for CAT (difference − 1.4: CI -2.3 to − 0.5) and CCQ (difference − 0.2: CI -0.3 to −0.1) using a five-point GRC.,The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values.,However, the design of the anchor question was likely to influence the MCID of CAT and CCQ.,RIMTCORE trial #DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer).,The online version of this article (10.1186/s12955-018-0950-7) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) remains a major public health problem that affects the quality of life of patients, however smoking cessation may emeliorate the functional effects of COPD and alter patient quality of life.,The aim of this study was to validate the Clinical COPD Questionnaire (CCQ) into Greek and with such to evaluate the quality of life in patients with different stages of COPD, as also assess their quality of life before and after smoking cessation.,The internal validity of questionnaire was high (Cronbach's a = 0.92).,The reliability of equivalent types in 16 stabilized patients also was high (ICC = 0.99).,In general the domains within the CCQ were strongly correlated with each other, while each domain in separate was strongly correlated with the overall CCQ score (r2 = 0.953, r2 = 0.915 and r2 = 0.842 in regards to the functional, symptomatic and mental domain, respectively).,The CCQ scores were also correlated with FEV1, (r2 = -0.252, p < 0.001), FEV1/FVC, (r2 = -0.135, p < 0.001) as also with the quality of life questionnaire SF-12 (r2 = -0.384, p < 0.001).,Smoking cessation also lead to a significant reduction in CCQ score and increase in the SF-12 score.,The self administered CCQ indicates satisfactory validity, reliability and responsiveness and may be used in clinical practice to assess patient quality of life.,Moreover the CCQ indicated the health related quality of life gains attributable to smoking cessation among COPD patients, projecting smoking cessation as a key target in COPD patient management. | 1 |
Airway inflammation persists after smoking cessation in established chronic obstructive pulmonary disease (COPD), suggesting that other factors drive the airway inflammatory response.,We tested the hypothesis that high levels of bacterial colonization are associated with increased levels of neutrophilic airway inflammation in stable COPD by examining the cross-sectional relationship between these measurements and by conducting a randomized, double-blind, placebo-controlled study of the effect of levofloxacin in patients with stable COPD.,Patients were randomized to receive either levofloxacin 500 mg daily or placebo for 7 days and underwent sputum induction for a differential cell count and quantitative bacterial analysis at baseline and at days 7, 14, and 28.,Sputum percentage neutrophil count correlated with airway bacterial load at baseline (r=0.56; P=0.003).,Levofloxacin reduced bacterial load compared with placebo by 4.9-fold (95% confidence interval, 1.4-25.7; P=0.02) at day 7 but had no effect at any point on any marker of neutrophilic airway inflammation.,In patients with a baseline bacterial load of more than 106 cfu/mL, levofloxacin treatment was associated with a 26.5% (95% confidence interval, 1.8%-51.3%; P=0.04) greater reduction in the percentage neutrophil count compared with placebo at day 7.,Change in percentage neutrophil count correlated significantly with baseline airway bacterial load and change in airway bacterial load.,In stable COPD, levofloxacin treatment causes a short-term reduction in bacterial load.,This is associated with a reduction in neutrophilic airway inflammation in patients with high bacterial loads.,Further studies are required to investigate whether this effect is clinically advantageous. | Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression.,However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established.,Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema.,We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.,Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity.,Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice.,Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice.,Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression.,Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS.,Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated.,Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.,Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression.,Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation. | 1 |
There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers.,We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking.,This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort.,During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer.,Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively.,In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status. | Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment.,More evidence is needed to guide antibiotic choice.,The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study.,Patients were aged ≥60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s <60% predicted and two or more exacerbations in the last year.,Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days).,The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population.,Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%).,In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016).,Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003).,Patients treated with oral corticosteroids had more severe disease and higher failure rates.,The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD.,Both therapies were well tolerated. | 1 |
Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited.,The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk.,Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date.,The data set contained potential risk factors including demographic, clinical, and comorbid variables.,Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression.,Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years.,The full predictive model was validated against 1 year of prospective OPCRD data.,The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data.,The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions.,Significant predictors not previously identified included eosinophilia and COPD Assessment Test score.,The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735).,Results of the sensitivity analyses supported the main findings.,Patients at risk of exacerbation can be identified from routinely available, computerized primary care data.,Further study is needed to validate the model in other patient populations. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD is highly complex and the underlying cellular and molecular mechanisms remain poorly understood.,A reliable, easy-to-measure, clinically relevant biomarker would be invaluable for improving outcomes for patients.,International and national guidance for COPD suggests using blood eosinophil counts as a biomarker to help estimate likely responsiveness to inhaled corticosteroids (ICS) and, potentially, to aid effective management strategies.,However, with the mechanism underlying the association between higher eosinophil levels and ICS effect unknown, use of the blood eosinophil count in COPD continues to be widely debated by the respiratory community.,Two international meetings involving respiratory medicine specialists, immunologists and primary and secondary care clinicians were held in November 2018 and March 2019, facilitated and funded by GlaxoSmithKline plc.,The aims of these meetings were to explore the role of eosinophils in the disease processes of COPD and as prognostic and diagnostic markers, and to identify areas of deficient knowledge that warrant further research.,The consensus views of the attendees on key topics, contextualised with current literature, are summarised in this review article, with the aim of aiding ongoing research into the disease processes of COPD and the development of biomarkers to aid clinical management.,Under certain conditions, eosinophils can be recruited to the lung, and increasing evidence supports a role for eosinophilic inflammation in some patients with COPD.,Infiltration of eosinophils across the bronchial vascular epithelium into the airways is promoted by the actions of immunoregulatory cells, cytokines and chemokines, where eosinophil-mediated inflammation is driven by the release of proinflammatory mediators.,Multiple studies and two meta-analyses suggest peripheral blood eosinophils may correlate positively with an increased likelihood of exacerbation reduction benefits of ICS in COPD.,The studies, however, vary in design and duration and by which eosinophil levels are viewed as predictive of an ICS response.,Generally, the response was seen when eosinophil levels were 100-300 cells/µL (or higher), levels which are traditionally viewed within the normal range.,Some success with interleukin-5-targeted therapy suggests that the eosinophilic phenotype may be a treatable trait.,The use of biomarkers could help to stratify treatment for COPD-the goal of which is to improve patient outcomes.,Some evidence supports eosinophils as a potential biomarker of a treatable trait in COPD, though it is still lacking and research is ongoing.,A unified consensus and a practical, accessible and affordable method of utilising any biomarker for COPD was thought to be of most importance.,Challenges around its utilisation may include presenting a clear and pragmatic rationale for biomarker-driven therapy, guidance on ICS withdrawal between primary and secondary care and a lack of financial incentives supporting broad application in clinical practice.,Future treatments should, perhaps, be more targeted rather than assuming the primary disease label (COPD or asthma) will define treatment response. | Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | 1 |
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