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Chronic obstructive pulmonary disease (COPD) clinical trials evaluating hard endpoints (mortality, hospitalized exacerbations) require a large number of subjects and prolonged observational periods.,We hypothesized that a composite endpoint of respiratory outcomes (CERO) can help evaluate safety and benefit in COPD trials.,Retrospective analysis of 5992 patients enrolled in the 4-year UPLIFT® trial, a randomized trial of tiotropium versus placebo in patients with moderate-to-severe COPD.,Patients were permitted to continue using their usual COPD medications except for other anticholinergics.,The CERO included deaths, respiratory failure, hospitalized exacerbations, and trial dropout due to COPD worsening.,The incidence rates (IRs) per 100 patient-years and risk ratios (RRs and 95 % CI) were determined at years 1 to 4.,The effect of treatments on CERO was similarly assessed.,A power analysis helped calculate the sample size needed to achieve outcome differences between treatments.,The CERO IRs at years 1 to 4 for tiotropium versus placebo were 16, 13, 11, and 11, and 21, 16, 14, and 13, respectively.,The RRs of CERO between tiotropium and placebo at the same time points were: RR-year 0.76 (0.67, 0.86), 0.80 (0.72, 0.88), 0.81 (0.74, 0.89), and 0.84 (0.77, 0.92).,Using the IRs and RRs, the sample size (alpha = 0.05 two-sided, 90 % power) for studies of 1, 2, 3, and 4 years would be 1546, 1392, 1216, and 1504 per treatment group, respectively, with 575, 810, 930, 1383 required events, respectively, for hypothetical, event-driven studies.,A composite endpoint incorporating relatively infrequent serious or significant COPD-related safety outcomes could be useful in clinical trials.,In UPLIFT®, CERO events were significantly reduced in patients receiving tiotropium compared with placebo.,NCT00144339.,The online version of this article (doi:10.1186/s12931-016-0361-4) contains supplementary material, which is available to authorized users. | The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year. | 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are important clinical events, with many patients experiencing multiple AECOPDs annually.,The terms used in the literature to define recurring AECOPD events are inconsistent and may impact the ability to describe the true burden of these events.,We undertook a systematic review to identify and summarize terms and definitions used in observational studies to describe AECOPD-related events occurring after an initial AECOPD (hereafter “subsequent AECOPD”).,PubMed was searched (2000-2019) for observational studies on subsequent AECOPD events using broad search strings for “COPD”, “exacerbation”, and “subsequent exacerbation events”.,Only English-language studies were included.,Small studies (n<50) and studies focusing on hospital re-admission only were excluded.,Extracted data were analyzed descriptively to generate a narrative summary, using a thematic approach to group studies utilizing similar terms for subsequent AECOPD.,Forty-seven studies were included.,No single, distinct terms or definitions were used to define and identify multiple occurrences of AECOPDs, though most (46) studies used one or more of four clustered terms and definitions: reapse (n = 13), recurrence/re-exacerbation (n = 11), treatment failure (n = 12) and non-recovery/time to recovery (n = 16).,Heterogeneity was observed within and between the four clusters with respect to study setting, starting point for observing subsequent AECOPDs, time frame to identify a subsequent AECOPD (except for studies using “time to recovery”), and basis for identifying a subsequent exacerbation.,Our review demonstrates that subsequent AECOPDs (including events such as relapse, recurrence/re-exacerbation, treatment failure, non-recovery/time to recovery) are ill-defined in the observational study literature, emphasizing the need to reach consensus on precise and objective definitions (for example, when one AECOPD ends and another begins).,Use of standardized terminology and definitions may aid comparability between, and synthesis of, studies, thus improving the understanding of the natural history and burden of exacerbations in COPD patients. | Patients with COPD may show slow, progressive deteriorations in arterial blood gases during the night, particularly during rapid eye movement (REM) sleep.,This is mainly due to hypoventilation, while a deterioration of ventilation/perfusion mismatch plays a minor role.,The severity of gas exchanges alterations is proportional to the degree of impairment of diurnal pulmonary function tests, particularly of partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2) in arterial blood, but correlations between diurnal and nocturnal blood gas levels are rather loose.,Subjects with diurnal PaO2 of 60-70 mmHg are distinguished in “desaturators” and “nondesaturators” according to nocturnal oxyhemoglobin saturation behavior.,The role of nocturnal hypoxemia as a determinant of alterations in sleep structure observed in COPD is dubious.,Effects of the “desaturator” condition on pulmonary hemodynamics, evolution of diurnal blood gases, and life expectancy are also controversial.,Conversely, it is generally accepted that occurrence of sleep apneas in COPD is associated with a worse evolution of the disease.,Nocturnal polysomnographic monitoring in COPD is usually performed when coexistence of sleep apnea (“overlap syndrome”) is suspected, while in most other cases nocturnal oximetry may be enough.,Nocturnal oxygen attenuates sleep desaturations among stable patients, without increases in PaCO2 of clinical concern.,Nocturnal treatment with positive pressure ventilators may give benefit to some stable hypercapnic subjects and patients with the overlap syndrome. | 1 |
Determination of markers of systemic inflammation is one of the important directions in the study of pathogenesis and improvement of diagnosis of chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and bronchial asthma (BA).,The aim of our work was a comparative study of the features of changes in serum levels of IL-17, IL-18, and TNF-α in patients with COPD, ACO, and BA with various severity of the disease, as well as evaluation of the relationship between the level of these cytokines and lung ventilation function.,A total of 147 patients with COPD (n = 58), ACO (n = 57), and BA (n = 32) during a stable period have been examined in this study.,The control group included 21 healthy nonsmokers with similar sex-age indicators.,Serum levels of IL-17, IL-18, and TNF-α were determined by ELISA.,The concentrations of these cytokines in the circulation in the studied patients with COPD, ACO, and BA were higher than those in healthy nonsmokers (p ≤ 0.001).,IL-17 and IL-18 levels in the blood serum were comparable in all examined patients.,The mean TNF-α concentrations in the circulation in COPD and ACO were significantly higher than those in BA (p < 0.001).,In patients with COPD, the levels of IL-17 and TNF-α increased progressively against the background of a decrease in numerous spirometric indicators, which allows us to consider these cytokines as systemic biomarkers of disease severity.,In BA, the inverse correlations between the level of IL-17 and FEV1/FVC (%) and FEV1 have been found.,In patients with ACO, the increase in IL-18 levels was associated with a decrease in FEV1 and TNF-α with FEV1/FVC (%).,These findings indicate that IL-17, IL-18, and TNF-α can participate in the mechanisms of systemic inflammation and the genesis of disorders of airway obstruction in COPD, AСO, and BA.,An increase in the levels of IL-17 and TNF-α may be associated with impaired bronchial patency in COPD and BA.,The established associations of the IL-18 concentration in the blood serum and FEV1 only in patients with ACO allow using the level of IL-18 as a potential marker of the degree of impaired airway obstruction in this disease. | Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response.,Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β.,The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations.,While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable.,In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines.,The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor.,Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD.,The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit.,Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either.,Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned.,There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target.,Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond. | 1 |
To assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease.,Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring.,68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission.,Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team.,Primary outcome measure was time to first hospital admission for an acute exacerbation.,Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford).,Median (IQR) number of days to first admission showed no difference between the two groups-77 (114) telemonitoring, 77.5 (61) control (p=0.189).,Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026).,Home visits increased during telemonitoring; GP consultations were unchanged.,Self-efficacy fell, while HAD depression score improved marginally during telemonitoring.,Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients.,NCT02180919 (ClinicalTrials.gov). | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.,A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed.,Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples.,Levels in patients colonized by H. influenzae and non-colonized patients were compared.,Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test).,Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test).,Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).,Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients.,Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases. | Nontypeable Haemophilus influenzae colonizes and infects the airways of adults with chronic obstructive pulmonary disease, the fourth most common cause of death worldwide.Thus, H. influenzae, an exclusively human pathogen, has adapted to survive in the hostile environment of the human airways.To characterize proteins expressed by H. influenzae in the airways, a prototype strain was grown in pooled human sputum to simulate conditions in the human respiratory tract.The proteins from whole bacterial cell lysates were solubilized with a strong buffer and then quantitatively cleaned with an optimized precipitation/on-pellet enzymatic digestion procedure.Proteomic profiling was accomplished by Nano-flow liquid chromatography/mass spectroscopy with low void volume and high separation efficiency with a shallow, long gradient.,A total of 1402 proteins were identified with high confidence, including 170 proteins that were encoded by genes that are annotated as conserved hypothetical proteins.Thirty-one proteins were present in greater abundance in sputum-grown conditions at a ratio of > 1.5 compared to chemically defined media.These included 8 anti-oxidant and 5 stress-related proteins, suggesting that expression of antioxidant activity and stress responses is important for survival in the airways.Four proteins involved in uptake of divalent anions and 9 proteins that function in uptake of various molecules were present in greater abundance in sputum-grown conditions.,Proteomic expression profiling of H. influenzae grown in pooled human sputum revealed increased expression of antioxidant, stress-response proteins and cofactor and nutrient uptake systems compared to media grown cells.These observations suggest that H. influenzae adapts to the oxidative and nutritionally limited conditions of the airways in adults with chronic obstructive pulmonary disease by increasing expression of molecules necessary for survival in these conditions. | 1 |
Tiotropium-olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), commercialized under the name of Spiolto or Stiolto.,The efficacy of tiotropium-olodaterol 5-5 μg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration.,Tiotropium-olodaterol 5-5 μg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance.,Improvements exceeded the minimal clinically important difference (MCID) for forced expiratory volume in 1 second (FEV1), dyspnea, and quality of life.,Differences between tiotropium-olodaterol 5-5 μg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID.,However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life.,Moreover, tiotropium-olodaterol 5-5 μg was significantly more effective than salmeterol-fluticasone (FDC) twice daily at improving pulmonary function.,Differences between tiotropium-olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers.,Therefore, tiotropium-olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy. | Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity.,Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes.,Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support.,We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study.,PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler.,Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity.,To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps.,This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations.,NCT02085161. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | 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 |
Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors.,Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness.,Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness.,In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted), arterial stiffness was assessed by augmentation index (AI).,Daily physical activity level (PAL) was measured by an activity monitor (SenseWear Pro™) >1 week.,The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities.,Patients suffered from moderate (35%), severe (32%), and very severe (33%) COPD, and 22% were active smokers.,Median (quartile) PAL was 1.4 (1.3/1.5) and mean (standard deviation) AI 26% (9.2%).,PAL showed a negative association with AI (B=−9.32, P=0.017) independent of age, sex, blood pressure, and airflow limitation.,In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk.,http://www.ClinicalTrials.gov, NCT01527773 | An essential element in the treatment of patients with chronic obstructive pulmonary disease (COPD) is rehabilitation, of which supervised training is an important part.,However, not all individuals with severe COPD can participate in the rehabilitation provided by hospitals and municipal training centres due to distance to the training venues and transportation difficulties.,The aim of the study was to assess the feasibility of an individualized home-based training and counselling programme via video conference to patients with severe COPD after hospitalization including assessment of safety, clinical outcomes, patients’ perceptions, organisational aspects and economic aspects.,The design was a pre- and post-test intervention study.,Fifty patients with severe COPD were included.,The telemedicine training and counselling included three weekly supervised exercise sessions by a physiotherapist and up to two supervised counselling and training sessions in energy conservation techniques by an occupational therapist.,The telemedicine videoconferencing equipment was a computer containing a screen, a microphone, an on/off switch and a volume control.,Thirty seven (74%) participants completed the programme, with improvements in health status assessed by the Clinical COPD Questionnaire and physical performance assessed by a sit-to-stand test and a timed-up-and-go test.,There were no cases of patient fall or emergency contact with a general practitioner during the telemedicine training sessions.,The study participants believed the telemedicine training and counselling was essential for getting started with being physically active in a secure manner.,The business case showed that under the current financing system, the reimbursement to the hospital was slightly higher than the hospital expenditures.,Thus, the business case for the hospital was positive.,The organizational analysis indicated that the perceptions of the staff were that the telemedicine service had improved the continuity of the rehabilitation programme for the patients and enabled the patients’ everyday lives to be included in the treatment.,This study showed that home-based supervised training and counselling via video conference is safe and feasible and that telemedicine can help to ensure more equitable access to supervised training in patients with severe COPD.,Clinical Trials NCT02085187 (Date of registration 10.03.2014). | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with cognitive impairment, but consequences of this association on a person’s functional limitations are unclear.,We examined the association between COPD and increased confusion and memory loss (ICML) and functional limitations among adults with COPD.,We studied adults aged 45 years or older in 21 states who participated in the 2011 Behavioral Risk Factor Surveillance System (n = 102,739).,Presence of COPD was based on self-reported physician diagnosis.,ICML was based on self-report that confusion or memory loss occurred more often or worsened during the prior year.,ICML-associated difficulties were defined as giving up household chores and former activities, decreased ability to work or engage in social activities, or needing help from family or friends during the prior year due to ICML.,General limitations were defined as needing special equipment as a result of a health condition, having had activity limitations for 2 weeks or more in the prior month, or being unable to work.,Multivariable models were adjusted for demographics, health behaviors or conditions, and frequent mental distress.,COPD was reported by 9.3% of adults.,ICML was greater among those with COPD than among those without COPD (25.8% vs 11%; adjusted prevalence ratio [aPR], 1.48; 95% confidence interval [CI], 1.32%-1.66%).,People with COPD, either with or without ICML, were more likely than those without COPD to report general functional limitations.,Among people reporting ICML, those with COPD were more likely to report interference with work or social activities than those without COPD (aPR, 1.17; 95% CI, 1.01%-1.36%).,Functional limitations were greater among those with COPD than among those without, and ICML may further affect these limitations.,Results from our study can inform future studies of self- management and functional limitations for people with COPD. | In the current study, the prevalence of the most common psychological disorders in COPD patients and their spouses was assessed cross-sectionally.,The influence of COPD patients’ and their spouses’ psychopathology on patient health-related quality of life was also examined.,The following measurements were employed: Forced expiratory volume in 1 second expressed in percentage predicted (FEV1%), Shuttle-Walking-Test (SWT), International Diagnostic Checklists for ICD-10 (IDCL), questionnaires on generic and disease-specific health-related quality of life (St.,George’s Respiratory Questionnaire (SGRQ), European Quality of Life Questionnaire (EuroQol), a modified version of a Disability-Index (CDI)), and a screening questionnaire for a broad range of psychological problems and symptoms of psychopathology (Symptom-Checklist-90-R (SCL-90-R)).,One hundred and forty-three stable COPD outpatients with a severity grade between 2 and 4 (according to the GOLD criteria) as well as 105 spouses took part in the study.,The prevalence of anxiety and depression diagnoses was increased both in COPD patients and their spouses.,In contrast, substance-related disorders were explicitly more frequent in COPD patients.,Multiple linear regression analyses indicated that depression (SCL-90-R), walking distance (SWT), somatization (SCL-90-R), male gender, FEV1%, and heart disease were independent predictors of COPD patients’ health-related quality of life.,After including anxiousness of the spouses in the regression, medical variables (FEV1% and heart disease) no longer explained disability, thus highlighting the relevance of spouses’ well-being.,The results underline the importance of depression and anxiousness for health-related quality of life in COPD patients and their spouses.,Of special interest is the fact that the relation between emotional distress and quality of life is interactive within a couple. | 1 |
Some patients share characteristics of both COPD and asthma.,As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS).,To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD.,Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics.,Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients.,Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared.,ACOS was diagnosed in 15.9% of the patients.,These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function.,They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E.,Within the ACOS group, only one-third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function.,ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD. | Overlap syndrome shares features of both asthma and chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate characteristics of overlap syndrome and their effect on self-rated health (SRH).,We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey of 2007-2009.,Subjects with acceptable spirometry and available wheezing history were included.,Subjects were classified into four groups based on forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) results and the presence or absence of self-reported wheezing for the previous 12 months: 1) COPD group, defined as having FEV1/FVC <0.7 without self-reported wheezing history; 2) asthma group, defined as having self-reported wheezing history without FEV1/FVC <0.7; 3) overlap syndrome group, having both FEV1/FVC <0.7 and wheezing history; and 4) non-obstructive disease (NOD) group, having neither FEV1/FVC <0.7 nor self-reported wheezing.,SRH was categorized as better or lower based on responses to a questionnaire.,From a total 9,104 subjects, 700 were assigned to the COPD group, 560 to the asthma group, 210 to the overlap syndrome group, and 7,634 to the NOD group.,Compared to the other groups, subjects in the overlap syndrome group were more likely to have low lung function, a high proportion of smokers, low socioeconomic status, short education duration, lower SRH, and past diagnosis of pulmonary tuberculosis or bronchiectasis.,Multiple logistic regression analysis revealed that both overlap syndrome and asthma groups were independently associated with lower SRH after adjustment for age, sex, socioeconomic status, education level, smoking status, comorbidities, and lung function.,Female, old age, low education level, low economic status, smoker and other comorbidities were also associated with lower SRH.,Overlap syndrome was accompanied by high morbidity and was associated with lower SRH, which needs more appropriate care. | 1 |
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users. | Inhaler device errors are common and may impact the effectiveness of the delivered drug.,There is a paucity of up-to-date systematic reviews (SRs) or meta-analyses (MAs) of device errors in asthma and chronic obstructive pulmonary disease (COPD) patients.,This SR and MA provides an estimate of overall error rates (both critical and non-critical) by device type and evaluates factors associated with inhaler misuse.,The following databases from inception to July 23, 2014 (Embase®, MEDLINE®, MEDLINE® In-Process and CENTRAL) were searched, using predefined search terms.,Studies in adult males and females with asthma or COPD, reporting at least one overall or critical error, using metered dose inhalers and dry powder inhalers were included.,Random-effect MAs were performed to estimate device error rates and to compare pairs of devices.,Overall and critical error rates were high across all devices, ranging from 50-100% and 14-92%, respectively.,However, between-study heterogeneity was also generally >90% (I-squared statistic), indicating large variability between studies.,A trend towards higher error rates with assessments comprising a larger number of steps was observed; however no consistent pattern was identified.,This SR and MA highlights the relatively limited body of evidence assessing device errors and the lack of standardised checklists.,There is currently insufficient evidence to determine differences in error rates between different inhaler devices and their impact on clinical outcomes.,A key step in improving our knowledge on this topic would be the development of standardised checklists for each device.,Researchers should adopt a standardised approach to investigate the incorrect use of inhalers and its associated clinical implications.,Henry Chrystyn at Plymouth University, together with scientists across the UK and the Netherlands, conducted a review of research related to inhaled medication errors made by patients with asthma or chronic obstructive pulmonary disease.,It is widely acknowledged that many patients with lung conditions don’t use their inhaler devices correctly, which affects drug effectiveness and disease control.,While Chrystyn’s team found high critical error rates reported across all devices, their meta-analysis and systematic review highlighted significant gaps in knowledge regarding different inhalers and associated error rates, and how these affect clinical outcomes.,The researchers call for in-depth studies into device use, alongside standardised checklists and definitions for such studies to use to ensure consistency. | 1 |
To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD. | We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. | 1 |
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. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by a largely irreversible airflow obstruction and a persistent, excessive inflammatory response.,Alveolar macrophages (AMs) are increased in the lungs of COPD patients, and act as orchestrators of the inflammatory response, releasing a range of mediators to coordinate recruitment and activation of leukocytes.,Attempts to treat the inflammatory component of COPD with anti-inflammatory drugs such as steroids has met with limited success.,In this study, we compared the ability of the phosphodiesterase IV (PDEIV) inhibitor Cilomilast, the steroid Budesonide, and the p38 mitogen activated protein kinase inhibitor BIRB-796 to inhibit tumour necrosis factor alpha (TNFα) and interleukin 6 (IL-6) releases from AMs isolated from COPD lung transplant tissue.,All studies were carried out with appropriate ethical approval and written, informed consent was obtained from each subject.,Cilomilast had little effect on cytokine release from AMs.,There was considerable variability in the responsiveness of AMs to Budesonide, with a subset of AMs responding poorly to Budesonide.,BIRB-796 inhibited TNFα release from all AM donors, including those that responded poorly to steroids.,Treatment with BIRB-796 and Budesonide together gave an additive decrease in TNFa release.,These results suggest that a p38 inhibitor may provide advantages over existing anti-inflammatory treatments for COPD, either as an add-on to existing therapy, or to treat patients who respond poorly to steroids. | Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder.,COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways.,We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.,Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects.,TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood.,CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors.,PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.,No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects.,However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells.,Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression.,CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ.,Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.,Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD.,CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.,These results provide a new perspective on the role of CD8+ T cells in COPD. | 1 |
Purpose: Women with chronic obstructive pulmonary disease (COPD) have more symptoms, more exacerbations, lower health status scores, and more comorbidity.,However, it is unclear whether management of COPD differs by sex.,The aim of the study was to investigate differences by sex in the care of patients with COPD.,Patients and methods: The population included 1329 primary and secondary care patients with a doctor´s diagnosis of COPD in central Sweden.,Data were obtained from patient questionnaires and included patient characteristics and data on achieved COPD care.,Analyses included cross-tabulations, chi-squared test and multiple logistic regression using several measures in COPD management as dependent variables, female sex as independent variable, and with adjustment for age groups, previous exacerbations, COPD Assessment Test, level of dyspnea assessed by the modified Medical Research Council scale, comorbid conditions, self-rated moderate/severe disease, level of education and body mass index.,Results: Women were more likely to receive triple therapy (OR 1.86 (95% CI 1.38-2.51)), to have any maintenance treatment (OR 1.82 (95% CI 1.31-2.55)), to be on sick leave (OR 2.16 (95% CI 1.19-3.93)), to have received smoking cessation support (OR 1.80 (95% CI 1.18-2.75)) and to have had pneumococcal vaccination (OR 1.82 (95% CI 1.37-2.43)), all independently of age, severity of disease or other potential confounders.,Conclusion: Management of COPD differs by sex, with women being more actively managed than men.,It is unclear whether this is due to patient- or care-related factors. | The influence of gender on the expression of COPD has received limited attention.,Quality of Life (QoL) has become an important outcome in COPD patients.,The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients.,In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year.,We explored differences between genders using Mann-Whitney U-rank test.,To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores.,Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01).,SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001).,In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001).,Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores.,In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores.,In turn, the clinical and physiological variables independently associated with those scores differed in men and women.,Attention should be paid to the determinants of QoL scores in women with COPD. | 1 |
Childhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults.,This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study.,We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants.,We evaluated current and former smokers ages 45-80 of non-Hispanic white (NHW) or African American (AA) race.,Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood.,Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation.,GWAS was performed in NHW and AA populations, and combined in meta-analysis.,Two sets of established asthma SNPs from published literature were examined for association with childhood asthma.,Among 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma.,Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81-4.18).,Genotype data was assessed for 8031 subjects.,Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8).,Among AAs, 339 (12%) had childhood asthma.,No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified.,Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS.,Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons).,Childhood asthmatics are at increased risk for COPD.,Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma.,This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens.,ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).,The online version of this article (10.1186/s12931-018-0890-0) contains supplementary material, which is available to authorized users. | Smoking is considered as the major causal factor of chronic obstructive pulmonary disease (COPD).,Nevertheless, a minority of chronic heavy cigarette smokers develops COPD.,This suggests important contribution of other factors such as genetic predisposing.,Our objective was to investigate combined role of EPHX1, GSTP1, M1 and T1 gene polymorphisms in COPD risk, its phenotypes and lung function impairment.,Prevalence of EPHX1, GSTP1, M1 and T1 gene polymorphisms were assessed in 234 COPD patients and 182 healthy controls from Tunisia.,Genotypes of EPHX1 (Tyr113His; His139Arg) and GSTP1 (Ile105Val; Ala114Val) polymorphisms were performed by PCR-RFLP, while the deletion in GSTM1 and GSTT1 genes was determined using multiplex PCR.,Analysis of combinations showed a significant association of 113His/His EPHX1/null-GSTM1 (OR = 4.07) and null-GSTM1/105Val/Val GSTP1 (OR = 3.56) genotypes with increased risk of COPD (respectively P=0.0094 and P=0.0153).,The null-GSTM1/ null-GSTT1, 105Val/Val GSTP1/null GSTT1, 113His/His EPHX1/null-GSTM1 and null-GSTM1/105Val/Val GSTP1 genotypes were related to emphysema (respectively P = 0.01; P = 0.009; P = 0.008 and P = 0.001).,Combination of 113His/His EPHX1/null-GSTM1 genotypes showed a significant association with the decrease of ΔFEV1 in patients (P = 0.028).,In conclusion, our results suggest combined EPHX1, GSTP1, GSTM1 and GSTT1 genetic polymorphisms may play a significant role in the development of COPD, emphysema and decline of the lung function. | 1 |
Early identification of preventable risk factors of COPD progression is important.,Whether exacerbations have a negative impact on disease progression is largely unknown.,We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.,Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied.,Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits.,Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.,Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation.,The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year.,Patients with more years with ≥1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations.,When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).,Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies. | Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage. | 1 |
Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients. | Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear.,We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.,Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007).,COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal.,Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry.,Model performance was assessed using standard criteria.,4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70.,The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76).,Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78).,The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).,Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD.,Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD. | 1 |
To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population.,Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010.,Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping.,Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline.,And another 9SNPs were selected from HapMap website as HHIP tags.,In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses.,We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population.,And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations.,These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population.,Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.,The online version of this article (doi:10.1186/s12931-015-0209-3) contains supplementary material, which is available to authorized users. | While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases.,We investigated whether different declines in air pollution levels in industrialised and rural areas in Germany were associated with changes in respiratory health over a period of about 20 years.,We used data from the SALIA cohort study in Germany (Study on the influence of Air pollution on Lung function, Inflammation and Aging) to assess the association between the prevalence of chronic obstructive pulmonary disease (COPD) and chronic respiratory symptoms and the decline in air pollution exposure.,In 1985-1994, 4874 women aged 55-years took part in the baseline investigation.,Of these, 2116 participated in a questionnaire follow-up in 2006 and in a subgroup of 402 women lung function was tested in 2008-2009.,Generalized estimating equation (GEE) models were used to estimate the effect of a reduction in air pollution on respiratory symptoms and diseases.,Ambient air concentrations of particulate matter with aerodynamic size < 10 μm (PM10) declined in average by 20 μg/m3.,Prevalence of chronic cough with phlegm production and mild COPD at baseline investigation compared to follow-up was 9.5% vs.,13.3% and 8.6% vs.,18.2%, respectively.,A steeper decline of PM10 was observed in the industrialized areas in comparison to the rural area, this was associated with a weaker increase in prevalence of respiratory symptoms and COPD.,Among women who never smoked, the prevalence of chronic cough with phlegm and mild COPD was estimated at 21.4% and 39.5%, respectively, if no air pollution reduction was assumed, and at 13.3% and 17.5%, respectively, if air pollution reduction was assumed.,We concluded that parallel to the decline of ambient air pollution over the last 20 years in the Ruhr area the age-related increase in chronic respiratory diseases and symptoms appears to attenuate in the population of elderly women. | 1 |
Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD. | 1 |
The topic of 24-hour management of COPD is related to day-to-night symptoms management, specific follow-up and patients’ adherence to therapy.,COPD symptoms strongly vary during day and night, being worse in the night and early morning.,This variability is not always adequately considered in the trials.,Night-time symptoms are predictive of higher mortality and more frequent exacerbations; therefore, they should be a target of therapy.,During night-time, in COPD patients the supine position is responsible for a different thoracic physiology; moreover, during some sleep phases the vagal stimulation determines increased bronchial secretions, increased blood flow in the bronchial circulation (enhancing inflammation) and increased airway resistance (broncho-motor tone).,Moreover, in COPD patients the circadian rhythm may be impaired.,The role of pharmacotherapy in this regard is still poorly investigated.,Symptoms can be grossly differentiated according to the different phenotypes of the disease: wheezing recalls asthma, while dyspnea is strongly related to emphysema (dynamic hyperinflation) or obstructive bronchiolitis (secretions).,Those symptoms may be different targets of therapy.,In this regard, GOLD recommendations for the first time introduced the concept of phenotype distinction suggesting the use of inhaled corticosteroids (ICS) particularly when an asthmatic pattern or eosiophilic inflammations are present, and hypothesized different approaches to target symptoms (ie, dyspnea) or exacerbations.,Pharmacotherapy should be evaluated and possibly directed on the basis of circadian variations, for instance, supporting the use of twice-daily rapid-action bronchodilators and evening dose of ICS.,Recommendations on day and night symptoms monitoring strategies and choice of the specific drug according to patient’s profile are still not systematically investigated or established.,This review is the summary of an advisory board on the topic “24-hour control of COPD and role of pharmacotherapy”, held by five pulmonologists, experts in respiratory pathophysiology, pharmacology and sleep medicine.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use:,https://youtu.be/RlA6NHUbnFY | Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD).,We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD.,Systematic review and meta-analysis.,MEDLINE, EMBASE and SCI were searched up to January 2015.,Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias.,We used the generic inverse variance method to pool effect estimates, where possible.,Evidence was synthesised in a narrative review where meta-analysis was not possible.,Searches yielded 8362 records, and 24 observational studies were included.,Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case-control studies: OR 1.18 (0.80 to 1.76).,Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7).,Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31).,However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40).,There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status.,There is some evidence that the risk of MI is higher during AECOPD than stable periods.,There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited.,This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.,This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016.,During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group.,The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.,Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25-75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).,According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group.,Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05).,Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.,Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization. | 1 |
Few data exist on the understanding and adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in resource-limited settings, which are mostly in sub-Saharan Africa.,To assess physicians' understanding, adherence, and barriers to implementation of GOLD guidelines in Nigeria.,A questionnaire based on the recommendations of the guidelines was self-administered by 156 physicians in departments of internal and family medicine in selected hospitals to assess physician understanding of the GOLD guidelines and barriers to its implementation.,The medical records of patients with chronic obstructive pulmonary disease (COPD) were also reviewed to assess adherence to the guideline recommendations.,The performance score of all physicians was 22.37±0.39 (range 0-38).,Pulmonologists had the highest score (37.00±0.00) while medical officers had the lowest score (19.93±4.98) (F=10.16, df=5, p<0.001).,Forty one percent of physicians knew the spirometric criteria for diagnosing COPD and 26.9% could assess the severity.,In clinical practice, 32% of patients had brief smoking counselling despite 70% being smokers, 24% had spirometry and 18% had assessment of severity.,Almost 60% of patients were on oral aminophylline, 72% were on an inhaled long-acting β2-agonist and corticosteroid combination, 2% had pulmonary rehabilitation and no patients were vaccinated.,Self-reported adherence to the COPD guidelines was 23.7%.,Lack of familiarity (39.8%) was cited as the most common barrier to adherence to the guidelines.,The understanding of GOLD guidelines is satisfactory among Nigerian doctors managing patients with COPD but the level of adherence is poor.,Educational interventions are needed to improve the implementation of guideline-based management. | The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used.,This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC.,This was a retrospective, cross-sectional study.,The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed.,Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point.,In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments.,In the discordant group, the CAT⩾10/mMRC 0-1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup.,Only moderate correlations existed between CAT and mMRC.,More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively.,A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale.,Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment.,The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide.,There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder.,However, additional research is required to improve our knowledge of these relationships and their possible implications.,In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD.,We conducted a cohort study in patients from the Taiwan Longitudinal Health Insurance Database between 2000 and 2013.,Patients with COPD were identified and assessed for pre-existing and incident DM.,A Cox proportional hazards model was built to identify factors associated with incident DM and to explore the prognostic effects of DM on COPD patients.,A propensity score method was used to match COPD patients with incident DM to controls without incident DM.,Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010-1.532] for mortality than that of the COPD patients without pre-existing DM.,During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363-2.403), cerebrovascular disease (HR, 1.517; 95% CI, 1.146-2.008) and coronary artery disease (HR, 1.408; 95% CI 1.089-1.820) were significant factors associated with incident DM.,Survival was worse for the COPD patients with incident DM than for the matched controls without incident DM (Log-rank, p = 0.027).,DM, either pre-existing or incident, was associated with worse outcomes in COPD patients.,Targeted surveillance and management of DM may be important in clinical care of the COPD population. | Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES. | 1 |
Purpose: Clinically important deterioration (CID) in chronic obstructive pulmonary disease (COPD) is a novel composite endpoint that assesses disease stability.,The association between short-term CID and future economic and quality of life (QoL) outcomes has not been previously assessed.,This analysis considers 3-year data from the TOwards a Revolution in COPD Health (TORCH) study, to examine this question.,Patients and methods: This post hoc analysis of TORCH (NCT00268216) compared costs and utilities at 3 years among patients without CID (CID-) and with CID (CID+) at 24 weeks.,A positive CID status was defined as either: a deterioration in forced expiratory volume in 1 second (FEV1) of ≥100 mL from baseline; or a ≥4-unit increase from baseline in St George’s Respiratory Questionnaire (SGRQ) total score; or the incidence of a moderate/severe exacerbation.,Patients from all treatment arms were included.,Utility change was based on the EQ-5D utility index.,Costs were based on healthcare resource utilization from 24 weeks to end of follow-up combined with unit costs for the UK (2016 GBP), and reported as per patient per year (PPPY).,Adjusted estimates were generated controlling for baseline characteristics, treatment assignment, and number of CID criteria met.,Results: Overall, 3,769 patients completed the study and were included in the analysis (stable CID- patients, n=1,832; unstable CID+ patients, n=1,937).,At the end of follow-up, CID- patients had higher mean (95% confidence interval [CI]) utility scores than CID+ patients (0.752 [0.738, 0.765] vs 0.697 [0.685, 0.71]; difference +0.054; P<0.001), and lower costs PPPY (£538 vs £916; difference: £378 [95% CI: £244, £521]; P<0.001).,The cost differential was primarily driven by the difference in general hospital ward days (P=0.003).,Conclusion: This study demonstrated that achieving early stability in COPD by preventing short-term CID is associated with better preservation of future QoL alongside reduced healthcare service costs. | The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD).,In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end.,The longitudinal changes in St George’s Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1).,The subjects were classified into the rapid decliners, slow decliners, and sustainers based on ΔFEV1/year.,The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile).,In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners.,Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index.,Larger reversibility was related to symptom component improvement.,Of the follow-up data, ΔFEV1/year was the best predictor for worsening of the components of SGRQ.,Continuous smoking was another factor for worsening of the activity component.,For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement.,The longitudinal changes of quality of life and their determinants are markedly different and independent between its components.,The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment. | 1 |
Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | Chronic obstructive pulmonary disease is a varied condition when examined from a number of different perspectives including factors which influence disease development, pathological process and clinical features.,There may be a complex interaction between the degree by which each of these processes influences the development of COPD and the subsequent clinical phenotype with which the patient presents.,The varied host response and subsequent clinical phenotype has generated much interest in recent years.,It is possible that failure of treatment to impact on mortality and reverse the disease process is because of the heterogeneous nature of the condition.,Identification and targeted treatment of clinical and pathological phenotypes within the broad spectrum of COPD may therefore improve outcome.,This article will review previous work which has attempted to phenotype COPD and identify if specific treatment for these phenotypes has been shown to be of benefit.,It will examine the work on pathological processes and clinical manifestations, both pulmonary and systemic, and will focus on pharmacological therapies. | 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 GOLD guidelines suggest that the presence of a post-bronchodilator forced expiratory volume in one second (FEV1) < 80% of the predicted value in combination with a FEV1/forced vital capacity (FVC) < 70% confirms the diagnosis of COPD.,Limited data exist regarding the accuracy of these criteria to distinguish between COPD and asthma.,The aim of this study therefore was to investigate the diagnostic value of post-bronchodilator lung function parameters in obstructive lung disease.,The pulmonary function tests of 43 (22 = COPD, 21 = asthma) patients with similar baseline characteristics were evaluated (baseline FEV1 were 55.7% ± 7.6%, and 59.3% ± 8.4% predicted for COPD and asthma, respectively).,Bronchodilator responsiveness (BDR) was calculated according to three recognized pulmonary function test criteria.,The first criteria, post-bronchodilator FEV1 < 80% of the predicted value in combination with a post-bronchodilator FEV1/FVC ratio of <70%, had an accuracy of 70% to diagnose COPD.,This combination was very sensitive (100%) in diagnosing COPD, but it was not specific (38%).,The second BDR criteria, defined as an increase of <12% and 200 mL of initial FEV1 and criterion number 3, an increase of < 9% of predicted FEV1, were less sensitive (55% and 59%, respectively), but more specific (81% and 76% respectively) to diagnose COPD.,Our findings suggest that the current recommended spirometric indices are not optimal in differentiating between COPD and asthma. | 1 |
Clin Microbiol Infect 2011; 17(Suppl.,6): E1-E59,This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010.,It provides evidence‐based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI.,Topics include management outside hospital, management inside hospital (including community‐acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention.,Background sections and graded evidence tables are also included.,The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI. | Chronic obstructive pulmonary disease (COPD) is a common inflammatory lung disease characterized by inflammatory cells activation and production of inflammatory mediators.,Methyl-CpG-binding domain protein 2 (MBD2) plays an important role in diverse immunological disorders by regulating immune cell functions, such as differentiation and mediator secretion.,However, the role of MBD2 in COPD remains unknown.,MBD2 protein expression in lung tissues of patients with COPD and cigarette smoke (CS)-exposed mice were evaluated by Western blot and immunohistochemistry.,The role of MBD2 in cigarette smoke extract (CSE)-induction of inflammatory mediator expression in the human bronchial epithelial (HBE) cell line was assessed by silencing MBD2 expression in vitro.,The involvement of signaling pathways in mediation of inflammation was tested with signaling inhibitors.,Compared with controls, MBD2 expression was distinctly reduced in the bronchial epithelium of both patients with COPD and CS-exposed mice.,Moreover, MBD2 expression was decreased in HBE after CSE stimulation in vitro.,Moreover, MBD2 knockdown enhanced interleukin (IL)-6 and IL-8 expression in HBE in the presence and absence of CSE treatment by the ERK signaling pathway.,MBD2 protein expression was reduced in the airway epithelium of COPD.,In HBE, this reduced expression was associated with increased levels of IL-6 and IL-8 mediated by the ERK pathway.,These results suggest that MBD2 could contribute to chronic airway inflammation in COPD. | 1 |
A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression.,Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.,33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects.,A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.,In COPD, compared to no-COPD, we found a faster lung function decline at follow-up.,Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced.,Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD.,The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001).,Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03).,No correlation was found between ΔFEV1, ΔCRP and ΔWBCs.,By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.,Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression.,Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease. | The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent.,Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent.,The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors.,Pathological changes in COPD are observed in central airways, small airways and alveolar space.,The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair.,Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70.,COPD is characterized by an accelerated decline in FEV1.,Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline.,The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy.,COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor.,Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support.,Lung volume reduction surgery and lung transplantation are advised in selected severe patients.,Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations. | 1 |
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes.,We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV1), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality.,MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019).,We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease.,We excluded studies of those with liver disease or drug-induced elevations in bilirubin.,We used the Newcastle-Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality-Evidence Based Practice tool to assess overall strength of evidence (SOE).,Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE.,Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included.,We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV1) (8 studies).,We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV1/FVC ratio) (4 studies).,Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes.,Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes.,PROSPERO registration: CRD42019145747. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis.,We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.,To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.7, FEV1% < 80%), and 30 non-COPD controls.,Targeted next generation sequencing was used to measure total and allele-specific expression of 35 genes in genome maintenance (GM) genes pathways linked to COPD pathogenesis, including seven TP53 and CEBP transcription factor family members.,Shrinkage linear discriminant analysis (SLDA) was used to identify COPD-classification models.,COPD GWAS were queried for putative cis-regulatory SNPs in the targeted genes.,On a network basis, TP53 and CEBP transcription factor pathway gene pair network connections, including key DNA repair gene ERCC5, were significantly different in COPD subjects (e.g., Wilcoxon rank sum test for closeness, p-value = 5.0E-11).,ERCC5 SNP rs4150275 association with chronic bronchitis was identified in a set of Lung Health Study (LHS) COPD GWAS SNPs restricted to those in putative regulatory regions within the targeted genes, and this association was validated in the COPDgene non-hispanic white (NHW) GWAS.,ERCC5 SNP rs4150275 is linked (D’ = 1) to ERCC5 SNP rs17655 which displayed differential allelic expression (DAE) in BEC and is an expression quantitative trait locus (eQTL) in lung tissue (p = 3.2E-7).,SNPs in linkage (D’ = 1) with rs17655 were predicted to alter miRNA binding (rs873601).,A classifier model that comprised gene features CAT, CEBPG, GPX1, KEAP1, TP73, and XPA had pooled 10-fold cross-validation receiver operator characteristic area under the curve of 75.4% (95% CI: 66.3%-89.3%).,The prevalence of DAE was higher than expected (p = 0.0023) in the classifier genes.,GM genes comprised by COPD-associated BEC expression patterns were enriched for SNPs with cis-regulatory function, including a putative cis-rSNP in ERCC5 that was associated with COPD risk.,These findings support additional total and allele-specific expression analysis of gene pathways with high prior likelihood for involvement in COPD pathogenesis.,The online version of this article (10.1186/s12890-018-0603-y) contains supplementary material, which is available to authorized users. | Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | 1 |
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation that is not fully reversible after inhaled bronchodilator use associated with an abnormal inflammatory condition.,The biggest risk factor for COPD is cigarette smoking.,The exposure to noxious chemicals contained within tobacco smoke is known to cause airway epithelial injury through oxidative stress, which in turn has the ability to elicit an inflammatory response.,In fact, the disruption of the delicate balance between oxidant and antioxidant defenses leads to an oxidative burden that has long been held responsible to play a pivotal role in the pathogenesis of COPD.,There are currently several biomarkers of oxidative stress in COPD that have been evaluated in a variety of biological samples.,The aim of this review is to identify the best studied molecules by summarizing the key literature findings, thus shedding some light on the subject.,We searched for relevant case-control studies examining oxidative stress biomarkers in stable COPD, taking into account the analytical method of detection as an influence factor.,Many oxidative stress biomarkers have been evaluated in several biological matrices, mostly in the blood.,Some of them consistently differ between the cases and controls even when allowing different analytical methods of detection.,The present review provides an overview of the oxidative stress biomarkers that have been evaluated in patients with COPD, bringing focus on those molecules whose reliability has been confirmed by the use of different analytical methods. | Chronic obstructive pulmonary disease (COPD) is a common airway disease characterized by an exaggerated pulmonary inflammatory response.,Long noncoding MIR155 host gene (lncRNA MIR155HG) has been identified to be related to the macrophage polarization in COPD.,However, the detailed function of MIR155HG in cigarette smoke (CS)-mediated COPD remains largely unknown.,The expression level of MIR155HG was elevated while miR-218-5p was decreased in lung tissues of smokers without or with COPD, especially in smokers with COPD, and cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cell (HPMECs) in a dose- and time-dependent manner.,Then, functional experiments showed that MIR155HG deletion could reverse CSE exposure-induced apoptosis and inflammation in HPMECs.,MiR-218-5p was confirmed to be a target of MIR155HG and rescue assay showed miR-218-5p inhibitor attenuated the inhibitory action of MIR155HG knockdown on CSE-induced HPMECs.,Subsequently, miR-218-5p was found to target bromodomain containing 4 (BRD4) directly, and miR-218-5p overexpression overturned CSE-induced injury of HPMECs via regulating BRD4.,Additionally, co-expression analysis indicated MIR155HG indirectly regulated BRD4 expression in HPMECs via miR-218-5p.,Thus, we concluded that MIR155HG contributed to the apoptosis and inflammation of HPMECs in smoke-related COPD by regulating miR-128-5p/BRD4 axis, providing a novel insight on the pathogenesis of COPD and a therapeutic strategy on COPD treatments. | 1 |
Data describing the potential relationship between chronic obstructive pulmonary disease (COPD) and body mass index (BMI) are limited within the Middle East and North Africa (MENA) region.,To evaluate the distribution of BMI among subjects with COPD in the general population of the MENA region.,This study was a subanalysis of the BREATHE study, a cross-sectional survey of COPD conducted in the general population of ten countries in the MENA region and Pakistan.,The study population consisted of subjects screened for COPD who documented their weight and height.,A COPD questionnaire was administered to subjects who screened positively for COPD in order to collect data on patient characteristics, symptom severity, management and burden of disease, comorbidities, and health care resource utilization and data allowing calculation of the BMI.,The COPD Assessment Test (CAT) was administered to those screened positively for COPD to collect data on the impact of respiratory symptoms.,Nine hundred and ninety-six subjects with COPD, who completed the detailed COPD questionnaire and documented their weight and height, were included in this analysis.,The mean BMI was 27.7±5.7 kg/m2.,The proportion of COPD patients with a BMI ≥25 kg/m2 is significantly higher than the proportion with a BMI <25 kg/m2 (64.6% [n=643] vs 35.4% [n=353], respectively; P<0.0001).,There were no significant differences between the distribution of BMI, ages, sex, COPD symptoms, exacerbations, CAT scores, COPD-associated health care resource consumption, and GOLD severity groups.,However, the occurrence of comorbidities such as diabetes and cardiovascular diseases seemed to be significantly associated with obese or morbidly obese status (P=0.02).,In the MENA region, the majority of COPD subjects were overweight or obese, and comorbidities such as diabetes or cardiovascular diseases are likely to be associated with COPD when BMI is in the obese or morbidly obese ranges. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
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. | 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 |
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | Interleukin (IL)-13, a T-helper type 2 cytokine, plays a critical role in the development of chronic obstructive pulmonary disease (COPD).,This meta-analysis was performed to assess the association of IL-13 −1112 C/T promoter polymorphism with COPD susceptibility.,Published case-control studies from Pubmed and China National Knowledge Infrastructure (CNKI) databases were retrieved.,Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.,Eight case-control studies in seven articles were included in this meta-analysis.,Pooled effect size showed IL-13 −1112 C/T was associated with COPD susceptibility in a codominant genetic model (TT vs CT, OR: 1.82, 95% CI: 1.14-2.92 and TT vs CC, OR: 2.02, 95% CI: 1.10-3.72), indicating individuals with TT genotype had an increased risk for COPD compared with those with CT or CC genotype.,According to ethnicity, results indicated IL-13 −1112 C/T was correlated with COPD susceptibility in Arabians (TT vs CT, OR: 2.94, 95% CI: 1.03-8.42 and TT vs CC, OR: 3.05, 95% CI: 1.08-8.59).,Moreover, after excluding the study without Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was found in this study.,This meta-analysis suggests IL-13 −1112 C/T promoter polymorphism is associated with the risk of COPD in Arabians. | 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. | The purpose of this study was to evaluate the frequency of inadequate diagnosis and factors predictive of this in patients with chronic obstructive pulmonary disease (COPD) participating in the On-Sint study.,The On-Sint cohort was recruited for a multicenter observational study in which 356 physicians (71.6% from primary care) included adult patients who had been diagnosed with COPD.,Patients’ clinical and functional information since diagnosis and details for the recruiting physicians were collected from patient files and at the inclusion visit.,We performed a multivariate analysis to evaluate the influence of these variables on diagnostic inadequacy (absence of postbronchodilator forced expiratory volume in one second/forced vital capacity [FEV1/FVC] <0.70 or, if this value was missing, prebronchodilator FEV1/FVC <0.70).,In total, 1,214 patients were included in the study.,The patients had a mean age of 66.4±9.7 years and 78.8% were male.,In total, 51.3% of patients did not have an obstructive spirometry performed, and 21.4% had a normal or non-obstructive spirometry pattern.,Patient-related factors associated with inadequate diagnosis were: years since diagnosis (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), number of exacerbations in the previous year (OR 1.01, 95% CI 1.01-1.02), comorbidities (OR 1.05, 95% CI 1.01-1.015), and obesity (OR 1.06, 95% CI 1.02-1.10 per kg/m2 of body mass index), while a longer smoking history (OR 0.98, 95% CI 0.97-0.99 for each pack/year) and short-acting or long-acting bronchodilator therapy (OR 0.61, 95% CI 0.44-0.76 and OR 0.46, 95% CI 0.27-0.76, respectively) were inversely related.,With regard to physician-related variables, being followed up by primary care physicians (OR 3.0, 95% CI 2.11-4.34) and in rural centers (OR 1.63, 95% CI 1.12-2.38) were positively associated with an inadequate diagnosis, while having regular follow-ups in the most severe cases (OR 0.66, 95% CI 0.46-0.93) and use of quality of life questionnaires (OR 0.55, 95% CI 0.40-0.76) were negatively associated.,Diagnosis of COPD was inadequate in half of the patients from the On-Sint cohort.,There were multiple factors, both patient-related and physician-related, associated with this misdiagnosis. | 1 |
Readmissions are common following acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and are partially responsible for increased morbidity and mortality in COPD.,Numerous factors have been shown to predict readmission of patients previously admitted to hospital for AECOPD; however, factors related to readmission in patients who are triaged in emergency departments (EDs) and sent directly home are poorly understood.,We postulate that patients seen in the ED for AECOPD and directly sent home have a high readmission rate, and we suspect that inadequate management and follow-up contribute to this high readmission rate.,We conducted a 1-year retrospective study of all patients seen in the ED for AECOPD at an inner-city tertiary care hospital; 30- and 90-day readmission rates for COPD and all-cause admissions to the ED and hospital were determined.,Patients discharged directly home from the ED were compared with those admitted to hospital for management.,Patient, treatment, and system variables that could potentially impact readmission were documented.,Multivariate Poisson regression models were used to determine which factors predicted readmissions.,The readmission rates in the ED group (n=240) were significantly higher than that in the hospitalized group (n=271): 1) the 90-day ED readmissions (1.29 vs 0.51, p<0.0001) and 30-day ED readmissions (0.54 vs 0.20, p<0.0001) (ED vs hospitalized groups) were significantly higher in the ED group; 2) the time to first readmission was significantly shorter in the ED group than in the hospitalized group (24.1±22 vs 31.8±27.8 days; p<0.05).,Cardiovascular comorbidities (p<0.00001), substance abuse disorder (p<0.001), and mental illness (p<0.001) were the strongest predictors of readmission in the ED group.,Age (p<0.01), forced expiratory volume in 1 second (p<0.001), and cardiovascular comorbidities (p<0.05) were the best predictors for both 30- and 90-day COPD readmission rates in the ED group.,Only 50% of the ED group patients received bronchodilators, oral steroids, and antibiotics inclusively, and only 68% were referred for community follow-up.,The need for oral steroids to treat AECOPD predicted future 90-day COPD readmissions in the ED group (p<0.003).,Patients discharged directly home from EDs have a significantly higher risk of readmission to EDs than those who are hospitalized.,One possible reason for this is that COPD management is variable in EDs with <50% receiving appropriate therapy. | COPD exacerbations and hospitalizations have been associated with poor prognosis for the COPD patient.,To evaluate the frequency and risk factors of COPD exacerbations, hospitalizations, and admissions to intensive care units (ICUs) in Greece by a nationwide cross-sectional study.,A nationwide observational, multicenter, cross-sectional study was conducted in the clinical practice setting of respiratory medicine physicians over a 6 month-period (October 2010 to March 2011).,A total of 6,125 COPD patients were recruited by 199 respiratory physicians.,Participants had a median age of 68.0 years, 71.3% were males, and 71.8% suffered from comorbidities.,The median disease duration was 10.0 years.,Of the patients, 45.3% were classified as having GOLD (Global initiative for chronic Obstructive Lung Disease) stage III or IV COPD.,Patients with four or more comorbidities had 78.5% and threefold-higher than expected number of exacerbations and hospitalizations, respectively, as well as fivefold-higher risk of admission to the ICU compared to those with no comorbidities.,Obese patients had 6.2% fewer expected exacerbations compared to those with a normal body mass index.,Patients with GOLD stage IV had 74.5% and fivefold-higher expected number of exacerbations and hospitalizations, respectively, and nearly threefold-higher risk of admission to the ICU compared to stage I patients.,An additional risk factor for exacerbations and hospitalizations was low compliance with treatment: 45% of patients reported forgetting to take their medication, and 81% reported a preference for a treatment with a lower dosing frequency.,Comorbidities, disease severity, and compliance with treatment were identified as the most notable risk factors for exacerbations, hospitalizations, and ICU admissions.,The results point to the need for a multifactorial approach for the COPD patient and for the development of strategies that can increase patient compliance with treatment. | 1 |
Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | 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 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | 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). | 1 |
COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. | Tiotropium is a potent, long-acting, selective anticholinergic bronchodilator.,Treatment with tiotropium produces sustained improvements in lung function, particularly FEV1 (peak, trough, average, and area under the curve) compared with either placebo or ipratropium in patients with moderate to severe COPD.,Preliminary evidence suggests that treatment with tiotropium may slow the rate of decline in FEV1, but this finding awaits confirmation.,Tiotropium reduces lung hyperinflation, with associated improvements in exercise capacity.,Tiotropium, compared with either placebo or ipratropium, improves a variety of patient-centered outcomes, including subjective dyspnea ratings and HRQL scores.,Tiotropium reduces the frequency of COPD exacerbations and of hospitalizations due to exacerbations, but has not been shown to reduce all-cause mortality.,Compared with the long-acting bronchodilators, tiotropium provides incrementally better bronchodilation, but it is not clearly superior in terms of patient-centered outcomes.,Tiotropium has a good safety profile; however patients with severe cardiac disease, bladder outlet obstruction, or narrow angle glaucoma were excluded from all studies.,Medico economic analyses suggest that treatment with tiotropium may also be cost-effective, primarily by reducing costs associated with hospitalizations. | 1 |
The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD).,Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice.,This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients.,This was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel.,Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms.,PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician’s judgement.,Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test.,The study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%).,Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity.,PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive.,By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary.,In any GOLD ABCD group, the percentage of inactive patients was high.,Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001).,Despite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms.,Physical activity level was low in this COPD cohort, and yet overestimated by physicians.,With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes.,NCT03031769, retrospectively registered, 23 Jan 2017.,The online version of this article (10.1186/s12931-019-1053-7) contains supplementary material, which is available to authorized users. | Multiple factors can influence the severity of chronic obstructive pulmonary disease (COPD) and the functioning of patients with COPD, such as personal characteristics and systemic manifestations.,To evaluate the different factors that can influence the activity and psychosocial impact domains of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients.,Participants, recruited in a university-based hospital, responded to the SGRQ, and in addition, personal, anthropometric, and clinical data were collected.,The study was approved by the Institutional Ethics Committee.,Data were analyzed using multiple linear regression models, with the SGRQ activity and psychosocial impact scores as outcome variables, and 10 explanatory variables (age, gender, forced expiratory volume in the first second - FEV1, smoking load, body mass index, oxygen therapy, associated diseases, regular physical activity, participation in a formal rehabilitation program, and SGRQ symptoms score) were considered.,The best regression model for predicting the SGRQ activity score (r2=0.477) included gender, FEV1, and SGRQ symptoms.,In contrast, the predictive model with the highest proportion of explained variance in psychosocial impact score (r2=0.426) included the variables gender, oxygen therapy, and SGRQ symptoms.,The results indicate that the outcomes, while based on functioning parameters in COPD patients, could be partly explained by the personal and clinical factors analyzed, especially by the symptoms assessed by the SGRQ.,Thus, it appears that the health conditions of these patients cannot be described by isolated variables, including pulmonary function parameters. | 1 |
Several inhaled drugs are dependent on organic cation transporters to cross cell membranes.,To further evaluate their potential to impact on inhaled drug disposition, the localization of MATE1, P-gp, OCTN1 and OCTN2 were investigated in human lung.,Transporter proteins were analysed by immunohistochemistry in lung tissue from healthy subjects and COPD patients.,Transporter mRNA was analysed by qPCR in lung tissue and in bronchoalveolar lavage (BAL) cells from smokers and non-smokers.,We demonstrate for the first time MATE1 protein expression in the lung with localization to the apical side of bronchial and bronchiolar epithelial cells.,Interestingly, MATE1 was strongly expressed in alveolar macrophages as demonstrated both in lung tissue and in BAL cells, and in inflammatory cells including CD3 positive T cells.,P-gp, OCTN1 and OCTN2 were also expressed in the alveolar epithelial cells and in inflammatory cells including alveolar macrophages.,In BAL cells from smokers, MATE1 and P-gp mRNA expression was significantly lower compared to cells from non-smokers whereas no difference was observed between COPD patients and healthy subjects.,THP-1 cells were evaluated as a model for alveolar macrophages but did not reflect the transporter expression observed in BAL cells.,We conclude that MATE1, P-gp, OCTN1 and OCTN2 are expressed in pulmonary lung epithelium, in alveolar macrophages and in other inflammatory cells.,This is important to consider in the development of drugs treating pulmonary disease as the transporters may impact drug disposition in the lung and consequently affect pharmacological efficacy and toxicity.,The online version of this article (10.1186/s12931-018-0760-9) contains supplementary material, which is available to authorized users. | Mutations in ATP-binding-cassette-member A3 (ABCA3) are related to severe chronic lung disease in neonates and children, but frequency of chronic lung disease due to ABCA3 mutations in the general population is unknown.,We tested the hypothesis that individuals heterozygous for ABCA3 mutations have reduced lung function and increased risk of COPD in the general population.,We screened 760 individuals with extreme pulmonary phenotypes and identified three novel (H86Y, A320T, A1086D) and four previously described mutations (E292V, P766S, S1262G, R1474W) in the ABCA3 gene.,We genotyped the entire Copenhagen City Heart study (n = 10,604) to assess the clinical importance of these mutations.,To validate our findings we genotyped an additional 54,395 individuals from the Copenhagen General Population Study.,In the Copenhagen City Heart Study individuals heterozygous for E292V had 5% reduced FEV1 % predicted compared with noncarriers (t-test: p = 0.008), and an increased odds ratio for COPD of 1.9 (95% CI: 1.1-3.1).,In contrast, the A1086D mutation was associated with increased FEV1 % predicted (p = 0.03).,None of the other ABCA3 mutations associated with lung function or COPD risk in the Copenhagen City Heart Study.,In the larger Copenhagen General Population Study, and in the two studies combined, E292V heterozygotes did not have reduced lung function or increased risk of COPD (p = 0.11-0.98), while this was the case for the positive controls, surfactant protein-B 121ins2 heterozygotes and α1-antitrypsin ZZ homozygotes.,Our results indicate that partially reduced ABCA3 activity due to E292V is not a major risk factor for reduced lung function and COPD in the general population.,This is an important finding as 1.3% in the Danish population has partially reduced ABCA3 function due to E292V. | 1 |
Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status.,Design Prospective, randomised controlled trial.,Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom.,Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193).,Main outcome measures The primary outcome was readmission rate at 12 months.,Secondary outcomes included number of hospital days, mortality, physical performance, and health status.,The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome.,Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission.,The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training.,Patients also received a self management and education package.,Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group).,No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4).,An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03).,Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year.,Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months.,Mortality at 12 months was higher in the intervention group.,The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.,Trial registration Current Controlled Trials ISRCTN05557928. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
The aim of this study is to summarize the evidence on the dose-response relationship between body mass index (BMI) and mortality in patients with chronic obstructive pulmonary disease (COPD).,We performed a systemic literature search in PubMed, Embase, and Web of Science for relevant studies that were published until June 2015.,A random effects meta-analysis was used to estimate the pooled relative risks (RRs) of all-cause mortality in COPD patients with normal weight compared with those who were underweight, overweight, or obese.,In addition, a dose-response meta-analysis was conducted to explore the dose-response relationship between BMI and all-cause mortality in COPD patients.,A total of 17 observational studies involving 30,182 COPD patients among 285,960 participants were included.,Compared with the reference category, the RRs of underweight, overweight, and obese individuals were 1.40 (95% confidence interval (CI), 1.20-1.63), 0.80 (95% CI, 0.67-0.96), and 0.77 (95% CI, 0.62-0.95), respectively.,A significant nonlinear relationship between BMI and mortality of COPD patients was found by using a random effects model.,COPD patients with BMI of <21.75 kg/m2 had a higher risk of death.,Moreover, an increase in the BMI resulted in a decrease in the risk of death.,The risk of death was lowest when BMI was 30 kg/m2 (RR = 0.69; 95% CI, 0.53-0.89).,The BMI was not associated with all-cause mortality when BMI was >32 kg/m2.,Our findings indicate that overweight is associated with a lower risk of all-cause mortality among patients with COPD whereas underweight is associated with a higher risk of all-cause mortality in these patients.,However, there is limited evidence to support the association between obesity and the risk of all-cause mortality in patients with COPD. | The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014.,The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St.,George’s Respiratory Questionnaire (SGRQ-C).,Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D).,Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%).,The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs.,0.9/0.1 vs.,1.2), as were the CAT score (13.9 vs.,18.3/13.5 vs.,18.1), mMRC (1.4 vs.,2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs.,42.9/29.1 vs.,42.6) compared to late-stage COPD (all P < 0.001).,Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%).,The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. | 1 |
Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | Telehealth is an approach to disease management, which may hold the potential of improving some of the features associated with COPD, including positive impact on disease progression, and thus possibly limiting further reduction in quality of life (QoL).,Our objective was, therefore, to summarize studies addressing the impact of telehealth on QoL in patients with COPD.,Systematic review.,A series of systematic searches were carried out using the following databases: PubMed, EMBASE, Cochrane Controlled Trials Register, and ClinicalTrials.gov (last updated November 2015).,A predefined search algorithm was utilized with the intention to capture all results related to COPD, QoL, and telehealth published since year 2000.,Primary outcome was QoL, assessed by validated measures.,Out of the 18 studies fulfilling the criteria for inclusion in this review, three studies found statistically significant improvements in QoL for patients allocated to telemedical interventions.,However, all of the other included studies found no statistically significant differences between control and telemedical intervention groups in terms of QoL.,Telehealth does not make a strong case for itself when exclusively looking at QoL as an outcome, since statistically significant improvements relative to control groups have been observed only in few of the available studies.,Nonetheless, this does not only rule out the possibility that telehealth is superior to standard care with regard to other outcomes but also seems to call for more research, not least in large-scale controlled trials. | 1 |
The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased.,Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD.,COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort.,ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/μL.,Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope.,Among 239 patients, 47 were diagnosed with ACO (19.7%).,During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting β2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO.,Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (− 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline.,Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.,The online version of this article (10.1186/s12931-018-0737-8) contains supplementary material, which is available to authorized users. | Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. | 1 |
To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD).,However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive.,In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population.,The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique.,Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008-1.811, P=0.044) compared with C allele.,Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06-4.989, P=0.035).,Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels.,Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls.,In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD. | Previous studies have suggested that β2-adrenergic receptor (ADRB2) is associated with COPD.,However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet.,In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively.,One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population.,Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034).,The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1.,In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017).,Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time. | 1 |
In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.,The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD.,Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014.,Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography.,One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis.,Six observational studies with 881 patients were included in the meta-analysis.,The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%.,Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history.,Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation.,In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. | Cardiovascular disease is a primary cause of death in patients with chronic obstructive pulmonary disease (COPD).,Beta-blockers have been proved to reduce morbidity and improve survival in patients with cardiac diseases.,But the effects of beta-blockers on outcomes in patients with COPD remain controversial.,The objective of this meta-analysis was to assess the effect of beta-blockers on mortality and exacerbation in patients with COPD.,An extensive search of the EMBASE, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with COPD.,The random effects model meta-analysis was used to evaluate effect on overall mortality and exacerbation of COPD.,Fifteen original observational cohort studies with a follow-up time from 1 to 7.2 years were included.,The results revealed that beta-blockers treatment significantly decreased the risk of overall mortality and exacerbation of COPD.,The relative risk (RR) for overall mortality was 0.72 (0.63 to 0.83), and for exacerbation of COPD was 0.63 (0.57 to 0.71).,In subgroup analysis of COPD patients with coronary heart disease or heart failure, the risk for overall mortality was 0.64 (0.54-0.76) and 0.74 (0.58-0.93), respectively.,The findings of this meta-analysis confirmed that beta-blocker use in patients with COPD may not only decrease the risk of overall mortality but also reduce the risk of exacerbation of COPD.,Beta-blocker prescription for cardiovascular diseases needs to improve in COPD patients. | 1 |
This study aims to investigate the relationship between post-diagnosis physical activity and mortality in patients with selected noncommunicable diseases, including breast cancer, lung cancer, type 2 diabetes, ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), osteoarthritis, low back pain and major depressive disorder.,A systematic search was conducted of PubMed, Scopus and the Web of Science from their inception to August 2018.,Additionally, the search was updated in August 2019.,Eligibility criteria included prospective observational studies examining the relationship between at least three physical activity categories (e.g. low, moderate, high) and all-cause mortality as the primary outcome.,In total, 28 studies were included in the meta-analysis: 12 for breast cancer, 6 for type 2 diabetes, 8 for ischemic heart disease and 2 for COPD.,The linear meta-analysis revealed that each 10 metabolic equivalent task hours increase of physical activity per week was associated with a 22% lower mortality rate in breast cancer patients (Summary Hazard Ratio [HR], 0.78; 95% CI: 0.71, 0.86; I2: 90.1%), 12% in ischemic heart disease patients (HR, 0.88; 95% CI: 0.83, 0.93; I2: 86.5%), 30% in COPD patients (HR, 0.70; 95% CI: 0.45, 1.09; I2: 94%) and 4% in type 2 diabetes patients (HR, 0.96; 95% CI: 0.93, 0.99; I2: 71.8%).,There was indication of a non-linear association with mortality risk reductions even for low levels of activity, as well as a flattening of the curve at higher levels of activity.,The certainty of evidence was low for breast cancer, type 2 diabetes and ischemic heart disease but only very low for COPD.,Higher levels of post-diagnosis physical activity are associated with lower mortality rates in breast cancer, type 2 diabetes, ischemic heart disease and COPD patients, with indication of a no-threshold and non-linear dose-response pattern. | Physical activity promotion in people with Chronic Obstructive Pulmonary Disease (COPD) is focus of research and public health.,Patient-centred interventions like counselling are promising approaches to help patients reducing sedentary behaviour.,Aim of the present study is to investigate if a physical activity counselling program during pulmonary rehabilitation increases physical activity level in daily life in people with COPD.,A two-armed, single blind randomised controlled trial including 56 people with COPD will be conducted in an outpatient pulmonary rehabilitation.,Patients will participate in a 12-week-rehabilitation program; individuals randomized to the interventional group will additionally participate in five counselling sessions with a physiotherapist, based on the principles of motivational interviewing.,The participants’ physical activity level will be measured using an accelerometer (SenseWear Pro®) before, directly and 3 months after pulmonary rehabilitation.,Semi-structured interviews will be conducted to learn more about barriers and facilitators regarding daily physical activity.,If the strategy successfully improves the physical activity level in people with COPD, counselling might be implemented in pulmonary rehabilitation.,Clinical Trials.gov NCT02455206 (05/21/2015), Swiss National Trails Portal SNCTP000001426 (05/21/2015). | 1 |
Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent.,This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective.,A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used.,Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2).,Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials).,Spanish utility values were derived from a published local observational study.,Unitary health care costs (€2015) were obtained from local sources.,A 3-year time horizon was selected, and 3% discount was applied to effects and costs.,Results were expressed as cost/quality-adjusted life years (QALYs).,Univariate and probabilistic sensitivity analysis (PSA) was performed.,UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY.,According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY.,UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective. | The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care.,This study aimed to evaluate its cost-effectiveness.,An economic analysis was performed from the Belgian healthcare payer’s perspective.,A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care.,Three types of costs were calculated: intervention costs, medication costs and exacerbation costs.,Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year.,Follow-up was 1 year in the basecase analysis.,Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.,In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon.,This reflects cost savings of €227 for the PHARMACOP-intervention.,The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care).,Results showed robust cost-savings in various sensitivity analyses.,Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies. | 1 |
Early detection of COPD may reduce the future burden of the disease.,We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV1 and FEV6) facilitates early detection of COPD in primary care.,In primary care, individuals at high risk of COPD (ie, age ≥35 years, relevant exposure, and at least one respiratory symptom) and no previous diagnosis of obstructive lung disease were examined with a COPD-6 screening device.,In prioritized order, the criteria for proceeding to confirmatory spirometry were FEV1/FEV6 <0.7, FEV1 <80%pred, or clinical suspicion of COPD regardless of test result (medical doctor’s [MD] decision).,Based on spirometry, including bronchodilator (BD) reversibility test, individuals were classified as COPD (post-BD FEV1/FVC <0.70), asthma (ΔFEV1 ≥0.50 L), or no obstructive lung disease.,A total of 2,990 subjects (54% men, mean age 59 years, and mean 28 pack-years) were enrolled, of whom 949 (32%) proceeded from COPD-6 screening to confirmative spirometry based on the following criteria: 510 (54%) FEV1/FEV6 <0.70, 382 (40%) FEV1 <80%pred, and 57 (6%) MD decision.,Following confirmative spirometry, the 949 individuals were diagnosed as having COPD (51%), asthma (3%), and no obstructive lung disease (45%).,COPD was diagnosed in 487 (16%) of the enrolled subjects in whom confirmative spirometry was performed in 69% based on FEV1/FEV6 <0.7 and in 29% based on FEV1 ≤80%pred.,Prescreening with the COPD-6 device showed acceptable specificity for the selection of subjects for diagnostic spirometry and is likely to be a useful alternative to current practice in primary care. | Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry.,This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.,This is a cross-sectional study performed on consecutive patients who were ≥40 years old with ≥10 pack-years smoking history.,Face-to-face interviews were carried out to obtain demographic data and relevant information.,Handheld spirometry was performed according to a standard protocol using the COPd-6 device (Model 4000, Vitalograph, Ennis, Ireland) in addition to standard spirometry.,Airflow limitation was defined as ratio of forced expiratory volume in 1 s (FEV1)/forced expiratory volume in 6 s <0.75 (COPd-6) or FEV1/forced vital capacity <0.7.,Multiple logistic regression analyses were used to determine predictors of airflow limitation.,A total of 416 patients were recruited with mean age of 53 years old.,The prevalence of airflow limitation was 10.6% (n = 44) with COPd-6 versus 6% as gauged using standard spirometry.,Risk factors for airflow limitation were age >65 years (odds ratio (OR) 3.732 95% confidence interval (CI): 1.100-1.280), a history of ‘bad health’ (OR 2.524, 95% CI: 1.037-6.142) and low to normal body mass index (OR 2.914, 95% CI: 1.191-7.190).,In a primary care setting, handheld spirometry (COPd-6) found a prevalence of airflow limitation of ∼10% in smokers.,Patients were older, not overweight and had an ill-defined history of health problems.,Prevalence of COPD is unknown in Malaysia.,The prevalence of COPD using a handheld spirometer (COPd-6TM) was 10.6% versus 6% as gauged using standard spirometry.,Predictors of COPD were older age, lower BMI and a history of ‘bad health’.,Case-finding for COPD should be targeted in this special population. | 1 |
Inhaled corticosteroids (ICS) are widely used in the treatment of chronic obstructive pulmonary disease (COPD), but recent studies have raised doubts whether all COPD patients will benefit from ICS.,This study evaluates in a real-life setting the effects of ICS withdrawal in patients with COPD.,The study was a prospective intervention study following patients with COPD for 6 months after abrupt withdrawal of ICS.,FEV1 (L), blood eosinophilic count (x10E9/L) and number of exacerbations were measured at baseline, 1, 3 and 6 months after ICS withdrawal.,Ninety-six patients (56 females (57.4%), mean age 70 years (51-94 years)) with COPD were included in the study.,Eleven patients were excluded during the study period (7 patients died, 4 patients withdrew their consent during the study period).,During the 6 months, 51 patients (60%) had resumed treatment with ICS, of whom 34 patients (68%) experienced an exacerbation during follow-up.,No significant decline in FEV1 was seen in this group between baseline and after 6 months (ΔFEV1 0.07 L, p = 0.09).,In the remaining 34 patients (40%) without ICS after 6 months of follow-up, 15 patients (44.1%) experienced an exacerbation.,No significant decline was seen in FEV1 at baseline and after 6 months (ΔFEV1 0.04 L, p = 0.28).,There were no statistically significant differences between the two groups in age (70.5 vs 69.6 years, p = 0.53), nor between FEV1 at baseline (0.96 L vs 1.00 L, p = 0.63) or eosinophilic count (0.25 x10E9/L vs 0.17 x10E9/L, p = 0.07).,Abrupt withdrawal of ICS was possible in some patients.,However, more than half of the patients resumed ICS during follow-up.,Based on results from our study we were not able to foresee - from neither history of exacerbations nor eosinophilic count - whom will be able to manage without ICS and who will resume treatment with ICS. | Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures. | 1 |
Chronic obstructive pulmonary disease (COPD) is set to become the third most frequent cause of death and also the third largest cause of global morbidity by 2020.,In China, where the population is aging rapidly, COPD has become one of the leading causes of disability and a large economic burden.,An epidemiological assessment of the COPD in China is required, with a focus on the number of cases living with disease, main determinants of the disease and time trends.,We systematically searched large Chinese bibliographic databases and English databases to identify spirometry-based epidemiological studies of the prevalence of COPD in China diagnosed according to GOLD criteria.,We estimated age- and gender-specific prevalence of COPD using a multilevel mixed-effect logistic regression.,We also presented the time trends of COPD between 1990 and 2010 by age, gender and setting (urban vs rural).,In 1990, the prevalence of COPD ranged from 0.49% (95% CI = 0.29-0.85) in <20 years group to 20.95% (95% CI = 14.04-27.04) in> = 80 years group, and the crude prevalence for China was 2.70% (95% CI = 1.86-3.51).,In 2010, the prevalence in <20 years was 0.55% (95% CI = 0.37-1.04) and in> = 80 years was 22.89% (95% CI = 18.13-28.96), with the crude prevalence for China of 3.84% (95% CI = 3.30-4.77).,The COPD prevalence in males was about two-fold higher than in females, and it increased with increasing age.,Between 1990-2010, the total number of Chinese people living with COPD increased by 66.73%, from 30.90 million (95% CI = 21.28-40.02) in 1990 to 51.52 million (95% CI = 44.26-63.93) in 2010.,This increase was most striking in middle age, and greater in females than in males from 30 years up to 64 years.,Our estimates, which used an independent approach to acquiring data and development of analytical methods, and were based on a more complete data set, are remarkably similar to those produced recently by the GBD 2013 collaboration, differing by only about 5% in the estimated number of COPD cases in 1990 and by 1% in 2010.,COPD is a highly prevalent disease in China and its importance is growing steadily.,The number of people living with COPD has increased substantially between 1990 and 2010.,COPD is more frequent in males and in rural areas.,Optimised primary and secondary prevention and treatment is urgently needed to counter this growing trend.,Improved epidemiological studies will be required to assist development of more effective strategies of prevention and treatment of COPD in China in the next decade and beyond. | Links between epithelial ion channels and chronic obstructive pulmonary diseases (COPD) are emerging through animal model and in vitro studies.,However, clinical correlations between fluid-regulating channel proteins and lung function in COPD remain to be elucidated.,To quantitatively measure epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporin 5 (AQP5) proteins in human COPD lungs and to analyze the correlation with declining lung function, quantitative western blots were used.,Spearman tests were performed to identify correlations between channel proteins and lung function.,The expression of α and β ENaC subunits was augmented and inversely associated with lung function.,In contrast, both total and alveolar type I (ATI) and II (ATII)-specific CFTR proteins were reduced.,The expression level of CFTR proteins was associated with FEV1 positively.,Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively.,Furthermore, these channel proteins were significantly associated with severity of disease.,Our study demonstrates that expression of ENaC, AQP5, and CFTR proteins in human COPD lungs is quantitatively associated with lung function and severity of COPD.,These apically located fluid-regulating channels may thereby serve as biomarkers and potent druggable targets of COPD. | 1 |
To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD.,We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo.,A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George’s Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24.,Inconsistency models were not statistically significant for all outcomes.,LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24.,All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1.,Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant.,LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement.,Similar trends were observed for the transition dyspnea index and St George’s Respiratory Questionnaire outcomes.,There were no significant differences in the incidences of adverse events among all treatment options.,LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement.,There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes. | Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | 1 |
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. | 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 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the commonest causes of hospital admission in Europe, Australasia, and North America.,These adverse events have a large effect on the health status of the patients and impose a heavy burden on healthcare systems.,While we acknowledge the contribution of pharmacotherapies to exacerbation prevention, our interpretation of the data is that exacerbations continue to be a major burden to individuals and healthcare systems, therefore, there remains great scope for other therapies to influence exacerbation frequency and preservation of quality of life.,In this review, the benefits and limitations of pulmonary rehabilitation, non-invasive ventilation, smoking cessation, and long-term oxygen therapy are discussed.,In addition, supported discharge, advanced care coordination, and telehealth programs to improve clinical outcome are reviewed as future directions for the management of COPD.,Please see related article: http://www.biomedcentral.com/1741-7015/11/181. | Clinical care components for people with COPD are recommended in guidelines if high-level evidence exists.,However, there are gaps in their implementation, and factors which act as barriers or facilitators to their uptake are not well described.,The aim of this pilot study was to explore implementation of key high-evidence COPD guideline recommendations in patients admitted to hospital with a disease exacerbation, to inform the development of a larger observational study.,This study recruited consecutive COPD patients admitted to a tertiary hospital.,Patient demographic, disease and admission characteristics were recorded.,Information about implementation of target guideline recommendations (smoking cessation, pulmonary rehabilitation referral, influenza vaccination, medication use and long-term oxygen use if hypoxaemic) was gained from medical records and patient interviews.,Interviews with hospital-based doctors examined their perspectives on recommendation implementation.,Fifteen patients (aged 76(9) years, FEV1%pred 58(15), mean(SD)) and nine doctors participated.,Referral to pulmonary rehabilitation (5/15 patients) was underutilised by comparison with other high-evidence recommendations.,Low awareness of pulmonary rehabilitation was a key barrier for patients and doctors.,Other barriers for patients were access difficulties, low perceived health benefits, and co-morbidities.,Doctors reported they tended to refer patients with severe disease and frequent hospital attendance, a finding supported by the quantitative data.,This study provides justification for a larger observational study to test the hypothesis that pulmonary rehabilitation referral is low in suitable COPD patients, and closer investigation of the reasons for this evidence-practice gap. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality.,Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD.,The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial.,Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted.,Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded.,Primary endpoint is change from baseline in aPWV after 24 weeks of treatment.,Safety analyses included adverse events (AEs).,The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141).,Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening.,At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo).,AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.,No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. | Little is known about factors that determine health status decline in clinical trials of COPD.,To examine health status changes over 3 years in the TORCH study of salmeterol+fluticasone propionate (SFC) vs. salmeterol alone, fluticasone propionate alone or placebo.,St George's Respiratory Questionnaire (SGRQ) was administered at baseline then every 6 months.,Data from 4951 patients in 28 countries were available.,SFC produced significant improvements over placebo in all three SGRQ domains during the study: (Symptoms -3.6 [95% CI -4.8, -2.4], Activity -2.8 [95% CI -3.9, -1.6], Impacts -3.2 [95% CI -4.3, -2.1]) but the pattern of change over time differed between domains.,SGRQ deteriorated faster in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III & IV relative to GOLD stage II (p < 0.001).,There was no difference in the relationship between deterioration in SGRQ Total score and forced expiratory volume in one second (FEV1) decline (as % predicted) in men and women.,Significantly faster deterioration in Total score relative to FEV1 % predicted was seen in older patients (≥ 65 years) and there was an age-related change in Total score that was independent of change in FEV1.,The relationship between deterioration in FEV1 and SGRQ did not differ in different world regions, but patients in Asia-Pacific showed a large improvement in score that was unrelated to FEV1 change.,In addition to treatment effects, health status changes in clinical trials may be influenced by demographic and disease-related factors.,Deterioration in health status appears to be fastest in older persons and those with severe airflow limitation.,ClinicalTrials.gov: NCT00268216 | 1 |
For patients with acute exacerbation of COPD (AECOPD), type 2 diabetes mellitus (T2DM) as comorbidity have poor outcomes.,However, data on the impact of previously diagnosed and new- diagnosed T2DM in such a patient population is lacking.,Inpatients diagnosed with AECOPD in the department of Pulmonary and Critical Care Medicine of The First Hospital of China Medical University during 2011-2017 were enrolled.,Data on demography, prevalence of type 2 DM, other comorbidities, hospital stays and laboratory tests (including arterial partial pressure of oxygen [PaO2]) results were recorded.,Results were compared with AECOPD patients having previously diagnosed and new-diagnosed type 2 diabetes.,Markers associated with development of type 2 DM and the prognosis of AECOPD patients were identified.,Of the 196 patients enrolled in this study, the overall prevalence of T2DM was 26%.,The PaO2 in the newly diagnosed T2DM group was considerably lower versus non-diabetic group.,The T2DM group had a longer hospital stay and higher troponin level versus the non-diabetic group.,AECOPD patients with T2DM were found to be correlated with hypertension.,Age, need for assisted ventilation, increased troponin, and elevated fasting blood glucose on admission were risk factors for death in hospitalized AECOPD patients.,AECOPD patients had a higher prevalence of T2DM than the general population; T2DM comorbidity caused lower PaO2, longer hospital stays, and increased troponin.,Poor blood glucose control may increase the risk of death in AECOPD patients. | Existing studies primarily explored chronic obstructive pulmonary disease (COPD) in smokers, whereas the clinical characteristics and the disease course of passive or nonsmokers have been rarely described.,In the present study, patients hospitalized and diagnosed as acute exacerbation of COPD (AECOPD) were recruited and followed up until being discharged.,Clinical and laboratory indicators were ascertained and delved into.,A total of 100 patients were covered, namely, 52 active smokers, 34 passive smokers, and 14 nonsmokers.,As revealed from the results here, passive or nonsmokers developed less severe dyspnea (patients with modified Medical Research Council scale (mMRC) <2, 0.0% vs.,8.8% vs.,14.3%, p < 0.05, active, passive, and nonsmokers, respectively), higher oxygenation index (206.4 ± 45.5 vs.,241.2 ± 51.1 vs.,242.4 ± 41.8 mmHg, p < 0.01), as well as lower arterial partial pressure of carbon dioxide (70.8 ± 12.7 vs.,58.85 ± 9.9 vs.,56.6 ± 6.5 mmHg, p < 0.001).,Despite lower treatment intensity over these patients, amelioration of dyspnea, mitigation of cough, and elevation of oxygenation index were comparable to those of active smokers.,However, in terms of patients exhibiting mMRC ≥2 and type 2 respiratory failure, amelioration of dyspnea was more common in nonsmokers as compared with passive smokers (46.4% vs.,83.3%, p < 0.05, passive and nonsmokers, respectively).,In terms of patients exhibiting Global Initiative for COPD severity <3, mMRC ≥2, and type 2 respiratory failure, active smokers achieved the least mitigation of cough symptom (8.7% vs.,35.0% vs.,44.4%, p < 0.05).,Similar results could be achieved after the effects of confounders were excluded, with the most prominent amelioration of dyspnea (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.1-13.6, p < 0.05, as compared with active smokers) and cough (OR 3.3, 95% CI 1.0-10.7, p < 0.05) in nonsmokers, and relatively better amelioration of hypoxemia in passive smokers (oxygenation index change, 39.0 ± 34.6 vs.,51.5 ± 32.4 vs.,45.3 ± 25.4 mmHg, p < 0.05).,In brief, passive or nonsmokers with AECOPD were subjected to less severe disease, and nonsmokers, especially patients with more severe disease, might achieve the optimal enhancement of clinical presentation after treatment. | 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. | Previous studies have suggested that β2-adrenergic receptor (ADRB2) is associated with COPD.,However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet.,In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively.,One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population.,Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034).,The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1.,In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017).,Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time. | 1 |
Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs.,Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated.,Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.,Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.,Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%).,No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline.,No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001).,In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02].,The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).,In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D.,This association was independent of patients’ characteristics and comorbidities.,The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users. | The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.,Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD.,Physician-diagnosed GERD was ascertained by questionnaire.,Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD.,We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models.,Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs).,To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.,GERD was reported by 29% of subjects with female predominance.,Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs.,13.4.0%, p < 0.0001).,Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs.,1.8, p < 0.0001), and poorer quality of life (QOL) scores (St.,George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs.,34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs.,41.4, p < 0.0001).,In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006).,During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included.,PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.,In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up.,These associations are maintained after controlling for PPI use.,The PPI-exacerbations association could result from confounding-by-indication. | 1 |
Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists.,We summarize evidence for various smoking indices.,Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking.,Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded.,Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment.,For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.,Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema.,RR estimates are markedly heterogeneous.,Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94).,For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition.,Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated.,For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function.,For all outcomes, risk increases with amount smoked and pack-years.,Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD.,No clear relationship is seen with duration of smoking.,The results confirm and quantify the causal relationships with smoking. | Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity.,Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.,The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells).,The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues.,To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.,In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue.,Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro when compared with control dendritic cells.,Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice.,Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress.,Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.,These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells.,Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD. | 1 |
Quantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD.,Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT.,We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT.,Portable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT.,Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt).,Thigh lean mass (Tdexa) was determined by DEXA.,Training resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively].,The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT.,Serial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD.,The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA.,http://www.controlled-trials.com (Identifier: ISRCTN22764439) | Multidetector-row computed tomography (MDCT) can be used to quantify morphological features and investigate structure/function relationship in COPD.,This approach allows a phenotypical definition of COPD patients, and might improve our understanding of disease pathogenesis and suggest new therapeutical options.,In recent years, magnetic resonance imaging (MRI) has also become potentially suitable for the assessment of ventilation, perfusion and respiratory mechanics.,This review focuses on the established clinical applications of CT, and novel CT and MRI techniques, which may prove valuable in evaluating the structural and functional damage in COPD. | 1 |
Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392. | An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use.,Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.,We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.,Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected.,Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205-2.762]) were independent risk factors for TB.,Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists.,Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB.,The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.,Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications.,Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment. | 1 |
Individuals with chronic obstructive pulmonary disease (COPD) commonly experience exacerbations, which may require hospital admission.,Early detection of exacerbations, and therefore early treatment, could be crucial in preventing admission and improving outcomes.,Our previous research has demonstrated that the pattern analysis of peripheral oxygen saturation (SpO2) fluctuations provides novel insights into the engagement of the respiratory control system in response to physiological stress (hypoxia).,Therefore, this pilot study tested the hypothesis that the pattern of SpO2 variations in overnight recordings of individuals with COPD would distinguish between stable and exacerbation phases of the disease.,Overnight pulse oximetry data from 11 individuals with COPD, who exhibited exacerbation after a period of stable disease, were examined.,Stable phase recordings were conducted overnight and one night prior to exacerbation recordings were also analyzed.,Pattern analysis of SpO2 variations was carried examined using sample entropy (for assessment of irregularity), the multiscale entropy (complexity), and detrended fluctuation analysis (self‐similarity).,SpO2 variations displayed a complex pattern in both stable and exacerbation phases of COPD.,During an exacerbation, SpO2 entropy increased (p = 0.029) and long‐term fractal‐like exponent (α2) decreased (p = 0.002) while the mean and standard deviation of SpO2 time series remained unchanged.,Through ROC analyses, SpO2 entropy and α2 were both able to classify the COPD phases into either stable or exacerbation phase.,With the best positive predictor value (PPV) for sample entropy (PPV = 70%) and a cut‐off value of 0.454.,While the best negative predictor value (NPV) was α2 (NPV = 78%) with a cut‐off value of 1.00.,Alterations in SpO2 entropy and the fractal‐like exponent have the potential to detect exacerbations in COPD.,Further research is warranted to examine if SpO2 variability analysis could be used as a novel objective method of detecting exacerbations.,This report provides evidence that the pattern of peripheral oxygen saturation (SpO2) fluctuations detects exacerbations in individuals with COPD.,The entropy of SpO2 signal increases a day prior to clinical diagnosis of exacerbation in COPD while mean and total variability of SpO2 signals remain unchanged.,This finding has potential for development of a non‐invasive method for early detection of exacerbations in COPD. | As the global burden of chronic disease rises, policy makers are showing a strong interest in adopting telehealth technologies for use in long term condition management, including COPD.,However, there remain barriers to its implementation and sustained use.,To date, there has been limited qualitative investigation into how users (both patients/carers and staff) perceive and experience the technology.,We aimed to systematically review and synthesise the findings from qualitative studies that investigated user perspectives and experiences of telehealth in COPD management, in order to identify factors which may impact on uptake.,Systematic review and meta-synthesis of published qualitative studies of user (patients, their carers and clinicians) experience of telehealth technologies for the management of Chronic Obstructive Pulmonary Disease.,ASSIA, CINAHL, Embase, Medline, PsychInfo and Web of Knowledge databases were searched up to October 2014.,Reference lists of included studies and reference lists of key papers were also searched.,Quality appraisal was guided by an adapted version of the CASP qualitative appraisal tool.,705 references (after duplicates removed) were identified and 10 papers, relating to 7 studies were included in the review.,Most authors of included studies had identified both positive and negative experiences of telehealth use in the management of COPD.,Through a line of argument synthesis we were able to derive new insights from the data to identify three overarching themes that have the ability to either impede or promote positive user experience of telehealth in COPD: the influence on moral dilemmas of help seeking-(enables dependency or self-care); transforming interactions (increases risk or reassurance) and reconfiguration of ‘work’ practices (causes burden or empowerment).,Findings from this meta-synthesis have implications for the future design and implementation of telehealth services.,Future research needs to include potential users at an earlier stage of telehealth/service development. | 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. | The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD).,The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD.,This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD.,It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers.,The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report.,This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations.,The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient.,The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS).,These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions.,For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms.,If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended.,For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice.,Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic.,If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast.,ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD.,Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD.,Thus, evidence-based recommendation of treatment cannot be given.,The treatment should cover both diseases.,Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both). | 1 |
Chronic obstructive pulmonary disease (COPD) remains a major health problem, strongly related to smoking.,Despite the publication of practice guidelines on prevention and treatment, not all patients with the disease receive the recommended healthcare, particularly with regard to smoking cessation advice where applicable.,We have developed a tailored implementation strategy for enhancing general practitioners’ adherence to the disease management guidelines.,The primary aim of the study is to evaluate the effects of this tailored implementation intervention on general practitioners’ adherence to guidelines.,A pragmatic two-arm cluster randomized trial has been planned to compare care following the implementation of tailored interventions of four recommendations in COPD patients against usual care.,The study will involve 18 general practices (9 in the intervention group and 9 in the control group) in Poland, each with at least 80 identified (at the baseline) patients with diagnosed COPD.,The nine control practices will provide usual care without any interventions.,Tailored interventions to implement four recommendations will be delivered in the remaining nine practices.,At follow-up after nine months, data will be collected for all 18 general practices.,The primary outcome measure is physicians’ adherence to all four recommendations: brief anti-smoking advice, dyspnea assessment, care checklist utilization and demonstration to patients of correct inhaler use.,This measurement will be based on data extracted from identified patients’ records.,Additionally, we will survey and interview patients with chronic obstructive pulmonary disease about the process of care.,The results of this trial will be directly applicable to primary care in Poland and add to the growing body of evidence on interventions to improve chronic illness care.,This trial has been registered with Clinical Trials Protocol Registration System.,Trial number: NCT01893476. | Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs).,The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines.,A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage.,Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis.,Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients.,In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05).,In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components.,Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow.,Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response.,Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability.,Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy.,Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence. | 1 |
Rationale: Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.,Objectives: To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations.,Methods: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.,The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set.,Measurements and Main Results: The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus.,The Haemophilus-predominant subgroup had elevated sputum IL-1β and TNFα (tumor necrosis factor α) and was relatively stable over time.,The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic.,Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations.,This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive.,Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time.,Network analysis revealed distinct host-microbiome interaction patterns among neutrophilic Haemophilus-predominant, neutrophilic balanced microbiome, and eosinophilic subgroups.,Conclusions: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies.,Neutrophilic and eosinophilic COPD are interchangeable in some patients.,Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
The TORRACTO® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment.,The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial.,Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients.,A total of 404 patients received treatment, with 165 participating in the ESWT substudy.,A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% (p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% (p = 0.14)] versus placebo.,In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% (p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% (p = 0.056)] versus placebo.,Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time.,[ClinicalTrials.gov identifier: NCT01525615.] | Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD).,We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.,Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout.,Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment.,The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.,A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted).,Ninety-five patients completed the study.,On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%.,Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study.,This was accompanied by inverse decreases in residual volume and functional residual capacity.,NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime).,The safety profile of NVA237 was similar to that of the placebo.,NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1.,This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea.,Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance.,(ClinicalTrials.gov Identifier: NCT01154127). | 1 |
Obesity/overweight is the most prevalent body composition abnormality in COPD.,However, little is known about the impact of fat distribution on cardiometabolic health in COPD.,To study the associations between ectopic adiposity, cardiometabolic health, and COPD.,A total of 263 subjects (166 males; age=65±9 years) were randomly selected from the general population.,Subjects were classified as non-COPD controls and COPD, according to the Global initiative for chronic Obstructive Lung Disease (GOLD) classification, and the presence of cardiometabolic comorbidities was recorded.,Ectopic fat accumulation was documented from computed tomography measurements of visceral adipose tissue cross-sectional areas and muscle mean attenuation, assessed at L4-L5.,Blood glucose, lipid, and adipokine profiles were also evaluated.,After correcting for age, sex, and tobacco exposure, visceral adipose tissue cross-sectional area was higher in GOLD 2+ compared to GOLD 1 individuals.,Consistent with this, mean muscle tissue attenuation was lower in GOLD 2+ vs GOLD 1 and non-COPD controls (P<0.001).,In multiple regression models, visceral adipose tissue cross-sectional area was strongly associated with hypertension (P<0.001) and diabetes (P<0.001), while muscle attenuation was associated with coronary artery disease (P<0.001).,Blood glucose, lipid, and adipokine profiles were similar across groups with the exception of leptin level which was higher in GOLD 2+ subjects compared to GOLD 1 and controls.,GOLD 2+ COPD was associated with ectopic fat accumulation which modulated cardiometabolic health. | The prevalence of metabolic syndrome in COPD patients and its impact on patient related outcomes has been little studied.,We evaluated the prevalence of metabolic syndrome and clinical and functional characteristics in patients with COPD and healthy subjects.,228 COPD patients and 156 healthy subjects were included.,Metabolic syndrome was defined using criteria of the IDF.,In all patients spirometry, body composition, functional exercise performance, and mood and health status were assessed.,Groups were stratified for BMI and gender.,Metabolic syndrome was present in 57% of the COPD patients and 40% of the healthy subjects.,After stratification for BMI, presence of metabolic syndrome in patients with a BMI ≥25 kg/m2 was higher than in healthy peers.,Patients with metabolic syndrome and a BMI <25 kg/m2 had higher BMI, fat free mass index and bone mineral density, and a lower 6MWD than the BMI matched patients without metabolic syndrome.,Spirometry, maximal ergometry, mood and health status, and blood gases were not different between those groups.,In COPD patients with metabolic syndrome self-reported co-morbidities and medication use were higher than in those without.,Metabolic syndrome is more prevalent in overweight or obese COPD patients than in BMI matched healthy subjects.,Metabolic syndrome did not additionally impact patients' functional outcomes, but did impact the prevalence of co-morbidities. | 1 |
Indacaterol is a novel, once-daily (o.d.) inhaled, long-acting β2-agonist in development for chronic obstructive pulmonary disease (COPD).,This 12-week, double-blind study compared the efficacy, safety, and tolerability of indacaterol to that of placebo in patients with moderate-to-severe COPD.,Efficacy variables included 24-h trough FEV1 (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (primary endpoint) and after Day 1, and the percentage of COPD days with poor control (i.e., worsening symptoms).,Safety was assessed by adverse events (AEs), mean serum potassium and blood glucose, QTc (Fridericia), and vital signs.,Patients were randomised (n = 416, mean age 63 years) to receive either indacaterol 150 μg o.d. (n = 211) or placebo (n = 205) via a single-dose dry-powder inhaler; 87.5% completed the study.,Trough FEV1 (LSM ± SEM) at Week 12 was 1.48 ± 0.018 L for indacaterol and 1.35 ± 0.019 L for placebo, a clinically relevant difference of 130 ± 24 mL (p < 0.001).,Trough FEV1 after one dose was significantly higher with indacaterol than placebo (p < 0.001).,Indacaterol demonstrated significantly higher peak FEV1 than placebo, both on Day 1 and at Week 12, with indacaterol-placebo differences (LSM ± SEM) of 190 ± 28 (p < 0.001) and 160 ± 28 mL (p < 0.001), respectively.,Standardised AUC measurements for FEV1 (between 5 min and 4 h, 5 min and 1 h, and 1 and 4 h post-dose) at Week 12 were all significantly greater with indacaterol than placebo (p < 0.001), with LSM (± SEM) differences of 170 ± 24, 180 ± 24, and 170 ± 24 mL, respectively.,Indacaterol significantly reduced the percentage of days of poor control versus placebo by 22.5% (p < 0.001) and was also associated with significantly reduced use of rescue medication (p < 0.001).,The overall rates of AEs were comparable between the groups (indacaterol 49.3%, placebo 46.8%), with the most common AEs being COPD worsening (indacaterol 8.5%, placebo 12.2%) and cough (indacaterol 6.2%, placebo 7.3%).,One patient died in the placebo group.,Serum potassium and blood glucose levels did not differ significantly between the two groups, and no patient had QTc >500 ms.,Indacaterol 150 μg o.d. provided clinically significant and sustained bronchodilation, reduced rescue medication use, and had a safety and tolerability profile similar to placebo.,NCT00624286 | 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 |
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. | 1 |
Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations.,Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations.,Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status.,ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone.,The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma-COPD overlap, may define a population of patients in whom ICSs may be of particular benefit.,Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed.,Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness.,The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids.,The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity.,ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used.,In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms.,Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment. | To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study.,Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan.,After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage.,Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively).,In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide.,In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients.,The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs. | 1 |
Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD).,We conducted a population-based case-control study to evaluate the effects of hypnotics on the risk of adverse respiratory events in patients with COPD.,The case-control study was investigated using data retrieved from the Taiwan National Health Insurance Research Database.,Patients with newly diagnosed adverse respiratory events (pneumonia, COPD with acute exacerbation, acute respiratory failure, and cardiopulmonary arrest) were included in the case group.,Patients with COPD and no history of adverse respiratory events were randomly selected for the control group, which was frequency-matched with the case group according to index date, age (per 10 years), and sex.,Patients who had used hypnotics within 1 month meant active users.,The odds ratios (ORs) and 95% confidence intervals (CIs) of were calculated using univariable and multivariable logistic regression models.,Most of the study participants were male (71.6%), and the mean ages of the participants in the case and control groups were 69.2 (±12.4) and 67.5 (±12.3) years, respectively.,After potential confounding factors were adjusting for, the adjusted ORs of adverse respiratory events were 12.0 for active users of benzodiazepines (95% CI, 8.11-17.6) and 10.5 for active users of nonbenzodiazepines (95% CI, 7.68-14.2) compared with the adjusted ORs of those who never used hypnotics.,The results of this epidemiological study suggested that hypnotics increased the risk of adverse respiratory events in patients with COPD. | It is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL.,This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities.,In the population-based KORA F4 study (2006-08) 1,321 participants aged 41-61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities.,For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999-2001) and the F4L follow-up study (2010).,Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups.,7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1.,Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered.,Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (−3.5 (p = 0.008) in F4, −3.3 (p = 0.014) in S4 and −4.7 (p = 0.003) in F4L) compared to the group without airflow limitation.,The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer.,Over ten years, a small decline in PCS-12 was observed in all groups.,This decline was larger in participants with COPD grade 2+, but insignificant.,Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found.,Despite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades.,Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system. | Chronic obstructive pulmonary disease (COPD) is a chronic lung disease, and the burden of COPD is expected to increase in the rapidly aging nation of South Korea.,This study aims to examine the factors contributing to health-related quality of life (HRQOL) in COPD patients.,This study was based on 6-year-data obtained from the Korean National Health and Nutrition Examination Survey 2007-2012.,COPD was diagnosed in 2,734 survey participants and the severity was graded according to the criteria set by the Global Initiative for Chronic Obstructive Lung Disease.,The EuroQol-5D (EQ-5D) index was used to assess the quality of life.,The EQ-5D index scores for COPD patients and the general population were 0.915±0.003 and 0.943±0.001, respectively.,Males, younger people, and patients with higher education attainment and income levels had a higher utility score.,In addition, the adjusted EQ-5D index scores for severity level IV significantly decreased by 0.100 (P=0.041), compared to the severity group I scores.,No significant differences were found in stage II and III patients.,Comorbidities (excluding cancer and hypertension) appeared to negatively influence HRQOL among COPD patients.,In particular, depression (EQ-5D index score =−0.089, P=0.0003) and osteoporosis (EQ-5D index score=−0.062, P=0.0039) had a significant influence, while smoking status did not appear to influence patient HRQOL.,In this study, we found that the higher the severity of COPD, the lower the quality of life.,In particular, patients with depression and osteoporosis had a relatively low utility score.,Therefore, these comorbidities should be carefully monitored in order to improve quality of life. | 1 |
Low health literacy is associated with low adherence to self-management in many chronic diseases.,Additionally, health beliefs are thought to be determinants of self-management behaviors.,In this study we sought to determine the association, if any, of health literacy and health beliefs among elderly individuals with COPD.,We enrolled a cohort of patients with COPD from two academic urban settings in New York, NY and Chicago, IL.,Health literacy was measured using the Short Test of Functional Health Literacy in Adults.,Using the framework of the Self-Regulation Model, illness and medication beliefs were measured with the Brief Illness Perception Questionnaire (B-IPQ) and Beliefs about Medications Questionnaire (BMQ).,Unadjusted analyses, with corresponding Cohen’s d effect sizes, and multiple logistic regression were used to assess the relationships between HL and illness and medication beliefs.,We enrolled 235 participants, 29% of whom had low health literacy.,Patients with low health literacy were more likely to belong to a racial minority group (p<0.001), not be married (p = 0.006), and to have lower income (p<0.001) or education (p<0.001).,In unadjusted analyses, patients with low health literacy were less likely to believe they will always have COPD (p = 0.003, Cohen’s d = 0.42), and were more likely to be concerned about their illness ((p = 0.04, Cohen’s d = 0.17).,In analyses adjusted for sociodemographic factors and other health beliefs, patients with low health literacy were less likely to believe that they will always have COPD (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.65-0.94).,In addition, the association of low health literacy with expressed concern about medications remained significant (OR: 1.20, 95% CI: 1.05-1.37) though the association of low health literacy with belief in the necessity of medications was no longer significant (OR: 0.92, 95% CI: 0.82-1.04).,In this cohort of urban individuals with COPD, low health literacy was prevalent, and associated with illness beliefs that predict decreased adherence.,Our results suggest that targeted strategies to address low health literacy and related illness and medications beliefs might improve COPD medication adherence and other self-management behaviors. | With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs).,To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs.,A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers.,The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol).,Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database.,Study outcomes were 1-year persistence and switching patterns.,Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities.,In all, 575 patients initiating LABAs were included in the final study cohort.,Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler.,Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol.,There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76-1.26, P=0.99).,Over 80% re-started or switched medication.,There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs.,Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. | 1 |
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients.,In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally.,Demographics, anthropometrics, lung function and clinical data were assessed.,Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband.,Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters.,Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns.,Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data.,Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all).,Daily physical activity measures and hourly patterns are heterogeneous in COPD.,Clusters of patients were identified solely based on physical activity data.,These findings may be useful to develop interventions aiming to promote physical activity in COPD. | In COPD patients, mortality risk is influenced by age, severity of respiratory disease, and comorbidities.,With an unbiased statistical approach we sought to identify clusters of COPD patients and to examine their mortality risk.,Stable COPD subjects (n = 527) were classified using hierarchical cluster analysis of clinical, functional and imaging data.,The relevance of this classification was validated using prospective follow-up of mortality.,The most relevant patient classification was that based on three clusters (phenotypes).,Phenotype 1 included subjects at very low risk of mortality, who had mild respiratory disease and low rates of comorbidities.,Phenotype 2 and 3 were at high risk of mortality.,Phenotype 2 included younger subjects with severe airflow limitation, emphysema and hyperinflation, low body mass index, and low rates of cardiovascular comorbidities.,Phenotype 3 included older subjects with less severe respiratory disease, but higher rates of obesity and cardiovascular comorbidities.,Mortality was associated with the severity of airflow limitation in Phenotype 2 but not in Phenotype 3 subjects, and subjects in Phenotype 2 died at younger age.,We identified three COPD phenotypes, including two phenotypes with high risk of mortality.,Subjects within these phenotypes may require different therapeutic interventions to improve their outcome. | 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma. | The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged ≥40 years), and pooled study results are presented herein.,Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension.,Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0-12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint.,Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint.,In the 26-week treatment period, significantly greater increases in FEV1 AUC0-12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P ≤ 0.032).,These increases were over three-fold greater with MF/F 400/10 than with MF 400.,Also, significantly greater increases in morning predose/trough FEV1 occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P < 0.05).,The increase was four-fold greater with MF/F 400/10 than with F 10.,All active treatment groups achieved minimum clinically important differences from baseline (>4 units) in St George’s Respiratory Questionnaire scores at week 26.,Symptom-free nights increased by ≥14% in the MF/F 400/10, MF 400, and F 10 groups (P ≤ 0.033 versus placebo).,The incidence of exacerbations was lower in the MF/F groups (≤33.3%) than it was in the MF, formoterol, and placebo groups (≥33.8%) over the 26-week treatment period.,The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment.,Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups.,Differences in rates of individual treatment-emergent adverse events were <3% between treatment groups.,Rates of pneumonia were low (≤2%) across all treatment groups.,Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates.,Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements. | 1 |
Evidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation.,We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation.,SOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction.,We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay.,In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay.,Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells.,We obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients.,Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels.,Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro.,Long-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation.,A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD. | To investigate the impact of exacerbations in health-related quality of life (HRQL) of patients with COPD and to compare the effect of treatment of COPD exacerbations with moxifloxacin (400 mg/day for 5 days) and amoxicillin/clavulanate (500/125 mg 3 times a day for 10 days) on HRQL.,229 outpatients with stable COPD (mean age 68.2 years; mean FEV1 % predicted 49.3%) participated in a prospective, observational study of 2 years’ duration.,The St George’s Respiratory Questionnaire (SGRQ) was completed at baseline and every 6 months thereafter.,COPD exacerbations (mean 2.7 episodes/patient) occurred in 136 patients (124 patients received the study medications [amoxicillin/clavulanate 54, moxifloxacin 70]).,Differences between baseline and the final visit were higher for moxifloxacin compared with amoxicillin/clavulanate for total SGRQ score (−2.60 [13.1] vs 4.21 [16.2], P = 0.05) and “Symptoms” subscale (−5.64 [16.7] vs 8.27 [21], P = 0.02).,The same findings were observed in patients with two or more exacerbations.,In COPD outpatients, treatment of exacerbations with moxifloxacin had a more favorable long-term effect on quality of life than amoxicillin/clavulanate. | 1 |
Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD).,However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.,We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.,In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera.,Haemophilus formed only 3% of the healthy microbiome.,In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively.,There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history.,Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).,The healthy and COPD sputum microbiomes are distinct and independent of smoking history.,Our results underline the important role for Gammaproteobacteria in COPD. | We recently published that platelet-activating factor receptor (PAFr) is upregulated on the epithelium of the proximal airways of current smokers and also in bronchial epithelial cells exposed to cigarette smoke extract.,These treated cells also showed upregulation of Streptococcus pneumoniae adhesion.,Bacterial wall phosphorylcholine specifically binds to PAFr expressed on airway epithelium, thus facilitating adherence and tissue invasion, which may be relevant to chronic obstructive pulmonary disease (COPD).,Moreover, the use of inhaled corticosteroids (ICS) in COPD patients is associated with an increased risk of invasive respiratory pneumococcal infections.,In this study, we have investigated whether PAFr expression is especially upregulated in airway epithelium in COPD patients and whether this expression may be modulated by ICS therapy.,We cross-sectionally evaluated PAFr expression in bronchial biopsies from 15 COPD patients who were current smokers (COPD-smokers) and 12 COPD-ex-smokers, and we compared these to biopsies from 16 smokers with normal lung function.,We assessed immunostaining with anti-PAFr monoclonal antibody.,We also used material from a previous double-blinded randomized placebo-controlled 6-month ICS intervention study in COPD patients to explore the effect of ICS on PAFr expression.,We employed computer-aided image analysis to quantify the percentage of epithelium stained for PAFr.,Markedly enhanced expression of PAFr was found in both COPD-smokers (P<0.005) and COPD-ex-smokers (P<0.002) compared to smokers with normal lung function.,There was little evidence that PAFr expression was affected by ICS therapy over 6 months.,Epithelial PAFr expression is upregulated in smokers, especially in those with COPD, and is not obviously affected by ICS therapy. | 1 |
Chronic obstructive pulmonary disease (COPD) is among the major health burdens in adults.,While cigarette smoking is the leading risk factor, a growing number of genetic variations have been discovered to influence disease susceptibility.,Epigenetic modifications may mediate the response of the genome to smoking and regulate gene expression.,Chromosome 19q13.2 region is associated with both smoking and COPD, yet its functional role is unclear.,Our study aimed to determine whether rs7937 (RAB4B, EGLN2), a top genetic variant in 19q13.2 region identified in genome-wide association studies of COPD, is associated with differential DNA methylation in blood (N = 1490) and gene expression in blood (N = 721) and lungs (N = 1087).,We combined genetic and epigenetic data from the Rotterdam Study (RS) to perform the epigenome-wide association analysis of rs7937.,Further, we used genetic and transcriptomic data from blood (RS) and from lung tissue (Lung expression quantitative trait loci mapping study), to perform the transcriptome-wide association study of rs7937.,Rs7937 was significantly (FDR < 0.05) and consistently associated with differential DNA methylation in blood at 4 CpG sites in cis, independent of smoking.,One methylation site (cg11298343-EGLN2) was also associated with COPD (P = 0.001).,Additionally, rs7937 was associated with gene expression levels in blood in cis (EGLN2), 42% mediated through cg11298343, and in lung tissue, in cis and trans (NUMBL, EGLN2, DNMT3A, LOC101929709 and PAK2).,Our results suggest that changes of DNA methylation and gene expression may be intermediate steps between genetic variants and COPD, but further causal studies in lung tissue should confirm this hypothesis. | Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses.,Also, miRNAs are dysregulated in smoking-associated diseases.,We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks.,After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant.,Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA.,In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD.,Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c.,Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. | 1 |
Necroptosis has emerged as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Here, we found that markers of necroptosis, including high mobility group box 1 release and phosphorylation of mixed lineage kinase domain-like protein (p-MLKL), were markedly induced in the late stage of cigarette smoking-induced (CS-induced) emphysema in mouse lung tissue as well as in lung epithelial cells and organoids with higher dosage of or more prolonged exposure to cigarette smoking extract (CSE).,Apoptotic signals were also detected and maximally induced in the early stage of CS-exposed mice and CSE-treated epithelial cells.,Inhibition of apoptosis by Z-VAD, a pan-caspase inhibitor, switched the cellular stress to enhanced necroptosis in lung epithelial cells and organoids treated with CSE.,Depletion or inhibition of receptor-interacting protein kinase 3 (RIP3) or MLKL attenuated the CSE-induced cell death, suggesting that necroptosis contributes to CSE-induced cell death.,Silencing or inhibition of RIP1 had no protective effect, indicating a RIP1-independent RIP3 activation pathway.,CSE-induced necroptosis released more damage-associated molecular patterns and evoked greater engulfment but slower clearance by bone marrow-derived macrophages, leading to enhanced expression of proinflammatory cytokines Tnfα and Il6.,Finally, our in vivo data verified that inhibition of necroptosis by RIP3 inhibitor GSK’872 protected mice from CS-induced emphysema and suppressed the lung inflammation.,In conclusion, we provide evidence that necroptosis contributes to the pathogenesis of COPD.,Targeting RIP3 and its downstream pathway may be an effective therapy for COPD. | Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD. | 1 |
Increased dyspnea, sputum volume, and purulence are subjective symptoms in COPD patients.,To diagnose COPD exacerbations with chronic respiratory failure (CRF) and to assess the requirement for antibiotic treatment, physicians require more objective criteria.,We aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR) can be used as an infectious exacerbation marker in COPD patients with CRF.,This retrospective cross-sectional study was performed in the intensive care outpatient clinic of a tertiary training hospital between 2014 and 2015.,Patients admitted with CRF due to COPD and who had complete blood count (CBC) results were enrolled.,CBC results and C-reactive protein (CRP) levels were obtained from the hospital online database.,The “modified exacerbation model (MEM)” was defined as follows: exacerbation A, leukocytes ≥12,000/mm3, CRP >10 mg/dL; exacerbation B, leukocytes ≥10,000/mm3, CRP >10 mg/dL; exacerbation C, leukocytes ≥10,000/mm3, CRP >8 mg/dL; exacerbation D, leukocytes ≥10,000/mm3, CRP >5 mg/dL.,The cutoff value of NLR was defined for each model.,Patients were split into two groups based on the NLR cutoff value according to the “NLR exacerbation model” and further subgrouped according to peripheral eosinophil percentage (eosinophils ≥2% and <2%) and compared with the MEM.,A total of 1,066 COPD patients (430 females, 40.3%), with a mean age of 66±13 years, were included.,A NLR cutoff value of 3.54 (NLR ≥3.54, n=366, 34%) showed the highest sensitivity and specificity for model A (78%, 69%), model B (63%, 71%), model C (61%, 72%), and model D (58%, 72%).,Peripheral eosinophilia (PE ≥2%) was present in 48 patients (4.5%).,The ratio of patients with PE <2% in the NLR ≥3.54 group was significantly higher in the MEM (P<0.001).,The NLR presents an attractive option as an exacerbation marker in COPD patients with CRF due to its simplicity and cost-effectiveness.,In COPD patients with CRF, where the NLR is ≥3.54, PE levels are <2%, and subjective symptoms are present, antibiotic treatment should be considered. | The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology.,This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD.,Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls.,The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden.,COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group.,Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m2, with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis.,The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year.,Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype.,No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers. | 1 |
Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β2 agonists have been shown to improve COPD outcomes.,Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures.,We investigated this using record linkage in a Dundee COPD population.,A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number.,A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders.,A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias.,4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study.,There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions.,The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively.,The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation.,There was however an association with increased cataracts and pneumonia hospitalisations. | 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 |
“Physical inactivity” and “sedentary lifestyles” are phrases often used when describing lifestyles of people with chronic obstructive pulmonary disease (COPD).,Evidence suggests activity types, independent of energy expenditure, influence health outcomes, so understanding patterns of time use is important, particularly in chronic disease.,We aimed to identify reports of time use in people with COPD.,Predefined search strategies were used with six electronic databases to identify individual activity reports (including frequencies and/or durations) in which community-dwelling people with COPD engaged.,Eligible studies were assessed independently against predefined criteria and data were extracted by two reviewers.,Data synthesis was achieved by aggregating activity reports into activity domains (sports/exercise, screen time, transport, quiet time, self-care, sociocultural, work/study, chores, and sleep).,Twenty-six publications reported 37 specific daily activities.,People with COPD were found to spend extended periods in sedentary behaviors (eg, standing [194 min/day]; sitting [359 min/day]; lying [88 min/day]), have limited engagement in physical activity (eg, walking [51 min/day]; exercising [1.2 episodes per week {ep/w}, 13 min/day]), have high health care needs (medical appointments [1.0 ep/w]), and experience difficulties associated with activities of daily living (eg, showering [2.5 ep/w, 60 minutes per episode]; preparing meals [4.7 ep/w]).,Little data could be found describing how people with COPD use their time, and data synthesis was problematic because of variations in methodologies, population differences, and research emphases.,Identified data largely referred to posture and were skewed according to country, assessment methods, and disease severity.,Comparisons with age-matched population data showed people with COPD spent less time engaged in personal-care activities (self-care and sleeping) and chores than people in similar age groups.,The incorporation of time-use outcomes in future research designs should be encouraged.,Ideally, these tools should use consistent frameworks and comparable outcome measures in order to provide clearer descriptions of time use in chronic disease. | Reduced physical activity is an important feature of Chronic Obstructive Pulmonary Disease (COPD).,Various activity monitors are available but their validity is poorly established.,The aim was to evaluate the validity of six monitors in patients with COPD.,We hypothesized triaxial monitors to be more valid compared to uniaxial monitors.,Thirty-nine patients (age 68±7years, FEV1 54±18%predicted) performed a one-hour standardized activity protocol.,Patients wore 6 monitors (Kenz Lifecorder (Kenz), Actiwatch, RT3, Actigraph GT3X (Actigraph), Dynaport MiniMod (MiniMod), and SenseWear Armband (SenseWear)) as well as a portable metabolic system (Oxycon Mobile).,Validity was evaluated by correlation analysis between indirect calorimetry (VO2) and the monitor outputs: Metabolic Equivalent of Task [METs] (SenseWear, MiniMod), activity counts (Actiwatch), vector magnitude units (Actigraph, RT3) and arbitrary units (Kenz) over the whole protocol and slow versus fast walking.,Minute-by-minute correlations were highest for the MiniMod (r = 0.82), Actigraph (r = 0.79), SenseWear (r = 0.73) and RT3 (r = 0.73).,Over the whole protocol, the mean correlations were best for the SenseWear (r = 0.76), Kenz (r = 0.52), Actigraph (r = 0.49) and MiniMod (r = 0.45).,The MiniMod (r = 0.94) and Actigraph (r = 0.88) performed better in detecting different walking speeds.,The Dynaport MiniMod, Actigraph GT3X and SenseWear Armband (all triaxial monitors) are the most valid monitors during standardized physical activities.,The Dynaport MiniMod and Actigraph GT3X discriminate best between different walking speeds. | 1 |
Initial use of inhaled corticosteroid therapy is common in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) A or B chronic obstructive pulmonary disease, contrary to GOLD guidelines.,We investigated UK prescribing of inhaled corticosteroid therapy in these patients, to identify predictors of inhaled corticosteroid use in newly diagnosed chronic obstructive pulmonary disease patients.,A cohort of newly diagnosed GOLD A/B chronic obstructive pulmonary disease patients was identified from the UK Clinical Practice Research Datalink (June 2005-June 2015).,Patients were classified by prescribed treatment, with those receiving inhaled corticosteroid-containing therapy compared with those receiving long-acting bronchodilators without inhaled corticosteroid.,In all, 29,815 patients with spirometry-confirmed chronic obstructive pulmonary disease were identified.,Of those prescribed maintenance therapy within 3 months of diagnosis, 63% were prescribed inhaled corticosteroid-containing therapy vs. 37% prescribed non-inhaled corticosteroid therapy.,FEV1% predicted, concurrent asthma diagnosis, region, and moderate exacerbation were the strongest predictors of inhaled corticosteroid use in the overall cohort.,When concurrent asthma patients were excluded, all other co-variates remained significant predictors.,Other significant predictors included general practitioner practice, younger age, and co-prescription with short-acting bronchodilators.,Trends over time showed that initial inhaled corticosteroid prescriptions reduced throughout the study, but still accounted for 47% of initial prescriptions in 2015.,These results suggest that inhaled corticosteroid prescribing in GOLD A/B patients is common, with significant regional variation that is independent of FEV1% predicted.,Inhaled steroids are often prescribed to early-stage chronic lung disease patients in the UK despite guidelines to the contrary.,Patients newly diagnosed with early-stage chronic obstructive pulmonary disease (COPD) should not be prescribed inhaled corticosteroids (ICS), because they carry an increased risk of side effects such as pneumonia and osteoporosis.,ICS should be reserved for patients with severe COPD and frequent exacerbations.,James Chalmers at the Scottish Centre for Respiratory Research, Dundee, and co-workers examined prescribed medication data from the UK spanning 10 years, to determine key predictors of ICS prescription during early-stage COPD.,Of 29,815 patients identified, an average of 63% were prescribed ICS upon diagnosis, regardless of disease severity.,Younger patients were more likely to receive ICS, possibly due to co-morbidity with chronic asthma, and particular UK regions and medical practices prescribed ICS more readily than others. | Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions.,The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit.,This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014.,Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible.,The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit.,The appropriateness of the performance was categorized as excellent (>80%), good (60−80%), adequate (40−59%), inadequate (20−39%), and highly inadequate (<20%).,During the audit, 621 clinical records were audited.,Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy.,The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations.,The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics.,Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved. | 1 |
In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations.,The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS).,Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce.,We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018.,All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1).,Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission.,Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted).,We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/μl and 2%).,Patients with low eosinophils (< 2%, <100 cells/μl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7 days).,The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs.,100-300: 13.5 vs.,> 300: 7.1 mg/dl).,Time to re-hospitalization or time to death did not differ between strata of eosinophils.,Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results.,The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation. | Blood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD).,We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort.,Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year.,85.3% of patients with eosinophils < 100 cells/μL had stable counts.,The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds. | 1 |
The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | Fatigue is a distressing, complex, multidimensional sensation common in individuals with chronic obstructive pulmonary disease (COPD).,While fatigue negatively impacts functional performance and quality of life, there has been little study of the fatigue that affects participants in pulmonary rehabilitation programs.,The purpose of this study was to examine the emotional, behavioral, cognitive, and physical dimensions of fatigue and their relationships to dyspnea, mental health, sleep, and physiologic factors.,A convenience sample of 42 pulmonary rehabilitation participants with COPD completed self-report questionnaires which measured dimensions of fatigue using the Multidimensional Fatigue Inventory, anxiety and depression using the Hospital Anxiety and Depression Scale, and sleep quality using the Pittsburgh Sleep Quality Index.,Data on other clinical variables were abstracted from pulmonary rehabilitation program health records.,Almost all (95.3%) participants experienced high levels of physical fatigue.,High levels of fatigue were also reported for the dimensions of reduced activity (88.1%), reduced motivation (83.3%), mental fatigue (69.9%), and general fatigue (54.5%).,Close to half (42.9%) of participants reported symptoms of anxiety, while almost one quarter (21.4%) reported depressive symptoms.,Age was related to the fatigue dimensions of reduced activity (ρ = 0.43, P < 0.01) and reduced motivation (ρ = 0.31, P < 0.05).,Anxiety was related to reduced motivation (ρ = −0.47, P < 0.01).,Fatigue was not associated with symptoms of depression, sleep quality, gender, supplemental oxygen use, smoking status, or Medical Research Council dyspnea scores.,Fatigue (particularly the physical and reduced motivation dimensions of fatigue) was experienced by almost all participants with COPD attending this pulmonary rehabilitation program.,Fatigue affected greater proportions of participants than either anxiety or depression.,The high prevalence of fatigue may impact on enrolment, participation, and attrition in pulmonary rehabilitation programs.,Further investigation of the nature, correlates, and impact of fatigue in this population is required. | 1 |
Clin Microbiol Infect 2011; 17(Suppl.,6): E1-E59,This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010.,It provides evidence‐based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI.,Topics include management outside hospital, management inside hospital (including community‐acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention.,Background sections and graded evidence tables are also included.,The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
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. | Eosinophilic airway inflammation is observed in 10-30% of COPD subjects.,Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.,We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year).,Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.,There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58).,Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01).,The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02).,Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).,Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation.,COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens.,Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections.,Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization.,Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD.,The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed.,As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus.,Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy.,Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality. | Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking.,Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress.,Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.,There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients.,Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema.,Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung.,Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.,In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed.,The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema. | 1 |
As Barthel Index (BI) quantifies motor impairment but not breathlessness, the use of only this index could underestimate disability in chronic respiratory disease (CRD).,To our knowledge, no study evaluates both motor and respiratory disability in CRD during activities of daily living (ADLs) simultaneously and with a unique tool.,The objective of this study was to propose for patients with CRD an additional tool for dyspnea assessment during ADLs based on BI items named Barthel Index dyspnea.,Comprehensibility, reliability, internal consistency, validity, responsiveness, and ability to differentiate between disease groups were assessed on 219 subjects through an observational study performed in an in-hospital rehabilitation setting.,Good comprehensibility, high reliability (interrater intraclass correlation coefficient was 0.93 [95% confidence interval 0.892-0.964] and test-retest intraclass correlation coefficient was 0.99 [95% confidence interval 0.983-0.994]), good internal consistency (Cronbach’s alpha 0.89), strong concurrent validity with 6 minute walking distance (Pearson r=−0.538, P<0.001) and Medical Research Council (Spearman rS=0.70, P<0.001), good responsiveness after rehabilitation (P<0.001), and good appropriateness of the index were found evidencing patients with different dyspnea severity.,Divergent validity showed weak correlation (Pearson r=−0.38) comparing Barthel Index dyspnea and BI.,The BI based on dyspnea perception proved to be reliable, sensitive, and adequate as a tool for measuring the level of dyspnea perceived in performing basic daily living activities.,A unique instrument simultaneously administered may provide a global assessment of disability during ADLs incorporating both motor and respiratory aspects. | Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs.,This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).,We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker.,We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model’s performance.,We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses.,Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0).,In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days.,The statistical model had an area under the receiver operating characteristic curve of 0.73.,Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS.,These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission.,However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use. | 1 |
Chronic obstructive pulmonary disease (COPD) is an increasingly prevalent lung disease linked to dysfunctional balance and an increased risk of falls.,The Balance Evaluation Systems Test (BESTest) evaluates the six underlying subcomponents of functional balance.,The aim of this study was to determine the specific balance subcomponents and cut-off scores that discriminate between fallers and non-fallers with COPD to guide fall risk assessment and prevention.,A secondary analysis of cross-sectional data from two prior studies in COPD was performed.,Independent samples t-tests were used to explore the differences in the BESTest sub-system scores between fallers and non-fallers.,Receiver operating characteristic curves were used to determine the optimal subcomponent cut-off scores that identified fallers, and the area under the curve (AUC) was used to assess test accuracy.,Data from 72 subjects with COPD (mean age, 70.3 ± 7.4y; mean forced expiratory volume in 1 second, 38.9 ± 15.8% predicted) were analyzed.,Two BESTest subcomponents, stability limits/verticality (fallers: 75.4%, non-fallers: 83.8%; p=0.002) and postural responses (fallers: 67.5%, non-fallers: 79.7%; p=0.008) distinguished between fallers and non-fallers.,Stability limits/verticality had an AUC of 0.70 and optimal cut-off score of 73.8% for identifying fallers; postural responses had an AUC of 0.67 and optimal cut-off score of 69.4%.,The stability limits/verticality and postural responses subcomponents of the BESTest distinguished between fallers and non-fallers with COPD.,The stability limits/verticality subcomponent can also be used to identify whether an individual with COPD is at risk of falling using a cut-off score of 73.8%.,These findings suggest that specific subcomponents of balance could be targeted to optimize fall risk assessment and prevention in COPD. | Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility.,Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD.,Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.,We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests.,The COPD patients were divided in two groups: emphysematous and bronchitic.,Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test.,We analyzed the differences in the balance tests between the studied groups.,Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001).,Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001).,Patients with COPD have a higher balance impairment than their healthy peers.,Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype. | 1 |
Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is characterized by irreversible airflow limitation based on obstructive bronchiolitis, emphysema, and chronic pulmonary inflammation.,Inhaled toxic gases and particles, e.g., cigarette smoke, are major etiologic factors for COPD, while the pathogenesis of the disease is only partially understood.,Over the past decade, an increasing body of evidence has been accumulated for a link between COPD and autoimmunity.,Studies with clinical samples have demonstrated that autoantibodies are present in sera of COPD patients and some of these antibodies correlate with specific disease phenotypes.,Furthermore, evidence from animal models of COPD has shown that autoimmunity against pulmonary antigens occur during disease development and is capable of mediating COPD-like symptoms.,The idea that autoimmunity could contribute to the development of COPD provides a new angle to understand the pathogenesis of the disease.,In this review article, we provide an advanced overview in this field and critically discuss the role of autoantibodies in the pathogenesis of COPD. | The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) carries a considerable economic burden, both for individuals and societies.,This study aimed to assess direct and indirect costs associated with COPD, and how costs vary across disease severity.,This was a nationwide, population-based cohort study utilizing Danish health registries.,Patients; ≥40 years of age, with an in- and/or outpatient diagnosis of COPD (ICD-10 J44) in 2008-2016, were identified in the nationwide Danish COPD Registry.,Included patients were matched 1:4 to a population-based non-COPD reference population of 196,623 individuals by sex, year of birth, co-habitation status, and municipality.,Patients were grouped by disease severity according to different characteristics including GOLD groups A-D, based on moderate (short-term oral corticosteroid use), presence of severe exacerbations (emergency visit or hospitalization) and symptom score.,Index was the date of the first outpatient visit with a symptom score registration.,The costs were calculated during a 12 months post-index follow-up.,In all, 49,826 patients with COPD (mean age 69.2 years, 52% females) were included.,Total annual costs, including direct costs, costs for elderly care, and costs for retirement home, were higher for patients with COPD (€28,969) compared with the reference population (€10,6913).,In GOLD groups A-D, the total direct costs were A: €8,766, B: €13,060, C: €11,113, and D: €17,749, respectively.,A major driver of direct costs was severe exacerbations.,The mean costs per moderate and severe exacerbation were €888 and €7,091, respectively, during 28 days of follow-up.,The costs for non-COPD-related Health Care Resource Utilization were higher than the COPD-related costs in GOLD groups A-C, but not in GOLD group D.,In this nationwide real-world study, total direct costs were three-fold higher among patients with COPD compared with the reference population.,Severe exacerbations were a major driver of the direct costs.,The costs increased with increasing disease severity. | The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | 1 |
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. | The fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).,This 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD.,The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin −50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84.,Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St.,George’s Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.,Trough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) −29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND.,The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference −23 mL; 95 % CI −54 to 8 mL).,The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores.,The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.,UMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.,ClinicalTrials.gov study ID NCT02257385; GSK study no.,116961.,The online version of this article (doi:10.1007/s40268-016-0131-2) contains supplementary material, which is available to authorized users. | 1 |
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