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Exacerbations of chronic obstructive pulmonary disease (COPD) are the third largest cause of emergency hospital admissions in the UK.,This systematic literature review explored the relationship between the hospitalization rates and the COPD comorbidities, anxiety, and depression.,The Centre for Research Dissemination’s framework for systematic reviews was followed using search terms relating to COPD, anxiety, depression, and hospital admission.,Papers identified were assessed for relevance and quality, using a suitable Critical Appraisal Skills Programme tool and Mixed Methods Assessment Tool.,Twenty quantitative studies indicated that anxiety and depression led to a statistically significant increase in the likelihood of COPD patients being hospitalized.,These comorbidities also led to an increased length of stay and a greater risk of mortality postdischarge.,Other significant factors included lower Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower socioeconomic status, poorer patient perceived quality of life, increased severity of lung function, and less improvement in dyspnea from admission to discharge.,It was also highlighted that only 27%-33% of those with depression were being treated for it.,Four qualitative studies revealed that patients saw anxiety and depression as a major factor that affected their ability to cope with and self-manage their condition.,Findings from the systematic review have highlighted a need for better recognition and treatment of anxiety and depression amongst individuals with COPD.,Ongoing research will develop and test strategies for promoting better management and self-management as a means of reducing hospital admissions. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
COPD self-management is a complex behavior influenced by many factors.,Despite scientific evidence that better disease outcomes can be achieved by enhancing self-management, many COPD patients do not respond to self-management interventions.,To move toward more effective self-management interventions, knowledge of characteristics associated with activation for self-management is needed.,The purpose of this study was to identify key patient and disease characteristics of activation for self-management.,An explorative cross-sectional study was conducted in primary and secondary care in patients with COPD.,Data were collected through questionnaires and chart reviews.,The main outcome was activation for self-management, measured with the 13-item Patient Activation Measure (PAM).,Independent variables were sociodemographic variables, self-reported health status, depression, anxiety, illness perception, social support, disease severity, and comorbidities.,A total of 290 participants (age: 67.2±10.3; forced expiratory volume in 1 second predicted: 63.6±19.2) were eligible for analysis.,While poor activation for self-management (PAM-1) was observed in 23% of the participants, only 15% was activated for self-management (PAM-4).,Multiple linear regression analysis revealed six explanatory determinants of activation for self-management (P<0.2): anxiety (β: −0.35; −0.6 to −0.1), illness perception (β: −0.2; −0.3 to −0.1), body mass index (BMI) (β: −0.4; −0.7 to −0.2), age (β: −0.1; −0.3 to −0.01), Global Initiative for Chronic Obstructive Lung Disease stage (2 vs 1 β: −3.2; −5.8 to −0.5; 3 vs 1 β: −3.4; −7.1 to 0.3), and comorbidities (β: 0.8; −0.2 to 1.8), explaining 17% of the variance.,This study showed that only a minority of COPD patients is activated for self-management.,Although only a limited part of the variance could be explained, anxiety, illness perception, BMI, age, disease severity, and comorbidities were identified as key determinants of activation for self-management.,This knowledge enables health care professionals to identify patients at risk of inadequate self-management, which is essential to move toward targeting and tailoring of self-management interventions.,Future studies are needed to understand the complex causal mechanisms toward change in self-management. | A substantial proportion of chronic disease patients do not respond to self-management interventions, which suggests that one size interventions do not fit all, demanding more tailored interventions.,To compose more individualized strategies, we aim to increase our understanding of characteristics associated with patient activation for self-management and to evaluate whether these are disease-transcending.,A cross-sectional survey study was conducted in primary and secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic Renal Disease (CRD).,Using multiple linear regression analysis, we analyzed associations between self-management activation (13-item Patient Activation Measure; PAM-13) and a wide range of socio-demographic, clinical, and psychosocial determinants.,Furthermore, we assessed whether the associations between the determinants and the PAM were disease-transcending by testing whether disease was an effect modifier.,In addition, we identified determinants associated with low activation for self-management using logistic regression analysis.,We included 1154 patients (53% response rate); 422 DM-II patients, 290 COPD patients, 223 HF patients and 219 CRD patients.,Mean age was 69.6±10.9.,Multiple linear regression analysis revealed 9 explanatory determinants of activation for self-management: age, BMI, educational level, financial distress, physical health status, depression, illness perception, social support and underlying disease, explaining a variance of 16.3%.,All associations, except for social support, were disease transcending.,This study explored factors associated with varying levels of activation for self-management.,These results are a first step in supporting clinicians and researchers to identify subpopulations of chronic disease patients less likely to be engaged in self-management.,Increased scientific efforts are needed to explain the greater part of the factors that contribute to the complex nature of patient activation for self-management. | 1 |
We have previously reported that the lungs of patients with very severe chronic obstructive pulmonary disease (COPD) contain significantly higher numbers of alveolar macrophages than those of non-smokers or smokers.,M1 and M2 macrophages represent pro- and anti-inflammatory populations, respectively.,However, the roles of M1 and M2 alveolar macrophages in COPD remain unclear.,Immunohistochemical techniques were used to examine CD163, CD204 and CD206, as M2 markers, expressed on alveolar macrophages in the lungs of patients with mild to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (mild) n = 11, II (moderate) n = 9, III (severe) n = 2, and IV (very severe) n = 16).,Fifteen smokers and 10 non-smokers were also examined for comparison.,There were significantly higher numbers of alveolar macrophages in COPD patients than in smokers and non-smokers.,The numbers and percentages of CD163+, CD204+ or CD206+ alveolar macrophages in patients with COPD at GOLD stages III and IV were significantly higher than in those at GOLD stages I and II, and those in smokers and non-smokers.,In patients with COPD, there was a significant negative correlation between the number of CD163+, CD204+ or CD206+ alveolar macrophages and the predicted forced expiratory volume in one second.,Overexpression of CD163, CD204 and CD206 on lung alveolar macrophages may be involved in the pathogenesis of COPD. | Macrophages have been implicated in the pathogenesis of COPD.,M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties.,We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD.,Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.,114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months).,BAL was collected from 71 patients.,CD163+ macrophages were quantified in BAL and sputum cytospins.,Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.,Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ×104/ml, p = 0.001 respectively).,The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001).,BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003).,No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.,Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. | 1 |
The diagnostic criteria of asthma-COPD overlap syndrome (ACOS) are controversial.,Emphysema is characteristic of COPD and usually does not exist in typical asthma patients.,Emphysema in patients with asthma suggests the coexistence of COPD.,Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively.,We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS.,This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects.,All the participants underwent pulmonary function tests and a high-resolution CT scan.,Emphysema measurements were taken with an Airway Inspector software.,The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units.,The characteristics of asthma patients with high EI were compared with those having low EI or COPD.,The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%.,COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls.,Thirty-two (21.2%) of the 151 asthma patients had high EI.,Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation.,There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients.,A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD.,Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines.,Quantitative CT measurements of emphysema may help in diagnosing ACOS. | The COPD assessment test (CAT) consists of eight nonspecific scores of quality of life.,The aim of this study was to compare the health-related quality of life and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome (ACOS) using the CAT.,We examined CAT and lung functions in 138 patients with asthma, 99 patients with COPD, 51 patients with ACOS, and 44 patients with chronic cough as a control.,The CAT score was recorded in all subjects, and the asthma control test was also administered to patients with asthma and ACOS.,The CAT scores were compared, and the relationships between the scores and lung function parameters were analyzed.,The total CAT scores and scores for cough, phlegm, and dyspnea were higher in patients with ACOS than in patients with asthma and COPD.,The total CAT scores were correlated with the percent predicted forced expiratory volume in 1 second only in patients with COPD.,The total CAT scores and dyspnea scores adjusted by the percent predicted forced expiratory volume in 1 second were higher in patients with ACOS than in patients with COPD and asthma.,The CAT scores and asthma control test scores were more closely correlated in patients with ACOS than in patients with asthma.,Patients with ACOS have higher disease impacts and dyspnea sensation unproportional to the severity of airflow limitation. | 1 |
The characteristics and natural history of GOLD B COPD patients are not well described.,The clinical characteristics and natural history of GOLD B patients over 1 year in a multicentre cohort of COPD patients in the COPDMAP study were assessed.,We aimed to identify the subgroup of patients who progressed to GOLD D (unstable GOLD B patients) and identify characteristics associated with progression.,Three hundred seventy COPD patients were assessed at baseline and 12 months thereafter.,Demographics, lung function, health status, 6 min walk tests and levels of systemic inflammation were assessed.,Students t tests and Mann Whitney-U tests were used.,One hundred seven (28.9%) of patients were categorised as GOLD B at baseline.,These GOLD B patients had similar FEV1 to GOLD A patients (66% predicted).,More GOLD B patients were current smokers (p = 0.031), had chronic bronchitis (p = 0.0003) and cardiovascular comorbidities (p = 0.019) compared to GOLD A.,At 12 months, 25.3% of GOLD B patients progressed to GOLD D.,These patients who progressed (unstable patients) had worse health status and symptoms (SGRQ-C Total, 50.0 v 41.1, p = 0.019 and CAT, 21.0 v 14.0, p = 0.006) and lower FEV1 (60% v 69% p = 0.014) at baseline compared to stable patients who remained in GOLD B.,Unstable GOLD B patients who progressed to GOLD D had a higher level of symptoms at baseline.,A high symptom burden may predict an increased likelihood of disease progression in GOLD B patients.,The online version of this article (doi:10.1186/s12890-017-0384-8) contains supplementary material, which is available to authorized users. | Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind. | 1 |
Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined.,Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed‐up for 1 year.,Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage.,Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation.,Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation.,The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A.,The Kaplan‐Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively.,The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation. | Current understanding of the relationship between COPD phenotype and health care resource utilization (HCRU) is limited.,This real-world study evaluated disease burden and HCRU for COPD subgroups prone to exacerbation as defined by blood eosinophil (EOS) count and multiple inhaler triple therapy (MITT) use.,This was a large-scale, retrospective, longitudinal, observational cohort study using data from the US IBM Watson Explorys real-world database (GSK Study HO-17-18395).,The population of interest comprised patients with COPD ≥40 years of age with ≥2 moderate or ≥1 severe exacerbations (prior year) while on inhaled maintenance therapy, with ≥1 blood EOS count.,Data were analyzed during the year prior to index date (last COPD encounter between January 1, 2011 and December 31, 2016).,Four subgroups were analyzed based on a combination of EOS counts (<150 and ≥150 cells/μL) and MITT use (receiving or not receiving).,Among these groups, clinical characteristics, exacerbations, and HCRU were described.,A sensitivity analysis that further stratified EOS into four categories (<150, ≥150-<300, ≥300-<500, and ≥500 cells/μL) was also performed.,The COPD population of interest comprised 34,268 patients.,Subgroups with EOS ≥150 cells/μL vs <150 cells/μL had more comorbidities and experienced significantly higher mean numbers of moderate exacerbations (not receiving MITT, ≥150 cells/μL vs <150 cells/μL: 1.93 vs 1.82, P<0.0001; receiving MITT 2.26 vs 2.16, P=0.0062) and COPD-related emergency visits (not receiving MITT, ≥150 cells/μL vs <150 cells/μL: 3.0 vs 2.5, P<0.001; receiving MITT 3.4 vs 3.1, P=0.0011).,Increasing EOS category was associated with higher HCRU.,Blood EOS ≥150/μL cells were associated with increased HCRU and higher exacerbation rates compared with EOS <150 cells/μL, irrespective of MITT use.,COPD phenotyping using blood EOS could help identify candidates for additional therapies that target eosinophilic inflammatory pathways. | 1 |
Despite the severe symptoms experienced by dying COPD patients, specialized palliative care (SPC) services focus mainly on cancer patients.,We aimed to study the access to SPC that COPD and lung cancer (LC) patients receive and how that access affects the need for acute hospital care.,A descriptive regional registry study using data acquired through VAL, the Stockholm Regional Council’s central data warehouse, which covers nearly all healthcare use in the county of Stockholm.,All the patients who died of COPD or LC from 2015 to 2019 were included.,T-tests, chi-2 tests, and univariable and multivariable logistic regression analyses were performed on the accumulated data.,In total, 6479 patients, (2917 with COPD and 3562 with LC) were studied.,The patients with LC had more access to SPC during the last three months of life than did those with COPD (77% vs. 18%, respectively; p < .0001), whereas patients with COPD were more likely to be residents of nursing homes than those with LC (32% vs. 9%, respectively; p < .0001).,Higher socioeconomic status (SES) (p < .01) and patient age < 80 years (p < .001) were associated with increased access to SPC for LC patients.,Access to SPC correlated with fewer emergency room visits (p < .0001 for both COPD and LC patients) and fewer admissions to acute hospitals during the last month of life (p < .0001 for both groups).,More COPD patients died in acute hospitals than lung cancer patients, (39% vs. 20%; χ2 = 287, p < .0001), with significantly lower figures for those who had access to SPC (p < .0001).,Compared to dying COPD patients, LC patients have more access to SPC.,Access to SPC reduces the need for emergency room visits and admissions to acute hospitals. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | 1 |
Physical activity (PA) is an important outcome parameter in patients with COPD regarding hospitalizations and mortality.,Both objective assessment by accelerometers and self-evaluation by questionnaires were used in studies investigating PA in COPD.,Whether self-reported questionnaires can adequately reflect PA and its changes over time compared to objective assessments has not been thoroughly investigated in COPD.,In this COPD cohort study, we evaluated whether PA measured by accelerometer and its annual changes can also be assessed by self-reported questionnaires.,In 178 COPD patients with at least two assessments of PA, the agreement between objectively measured and self-reported activity was analyzed by Bland-Altman plots.,Daily PA was assessed by a triaxial activity monitor over 1 week and by the self-reported German PA questionnaire 50+.,Comparison between the two methods of measurement revealed no convincing agreement with a mean difference and limits of agreement (±1.96 standard deviation [SD]) of time spent in at least moderate PA (>3 metabolic equivalent of task [MET]) of −77.6 (−340.3/185.2) min/day, indicating a self-reported overestimation of PA by the questionnaire.,The mean difference and limits of agreement (±1.96SD) in the annual change of PA was 1.2 min/day (−208.2/282.6 min/day), showing also a poor agreement on an individual level.,Evaluation of objectively measured and self-reported PA and their annual changes revealed no agreement in patients with COPD.,Therefore, the evaluated questionnaire seems not helpful for measurement of PA and its changes over time. | COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs).,Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations.,In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count.,We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St.,George's Respiratory Questionnaire Activity Score (SGRQ-AS).,AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months.,Mean daily step count was 5804±3141 steps.,Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year).,Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42).,There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003).,Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations.,Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations.,Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history.,These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies. | 1 |
To develop a practicable nomogram aimed at predicting the risk of severe exacerbations in COPD patients at three and five years.,COPD patients with prospective follow-up data were extracted from Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) obtained from National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center.,We comprehensively considered the demographic characteristics, clinical data and inflammation marker of disease severity.,Cox proportional hazard regression was performed to identify the best combination of predictors on the basis of the smallest Akaike Information Criterion.,A nomogram was developed and evaluated on discrimination, calibration, and clinical efficacy by the concordance index (C-index), calibration plot and decision curve analysis, respectively.,Internal validation of the nomogram was assessed by the calibration plot with 1000 bootstrapped resamples.,Among 1711 COPD patients, 523 (30.6%) suffered from at least one severe exacerbation during follow-up.,After stepwise regression analysis, six variables were determined including BMI, severe exacerbations in the prior year, comorbidity index, post-bronchodilator FEV1% predicted, and white blood cells.,Nomogram to estimate patients’ likelihood of severe exacerbations at three and five years was established.,The C-index of the nomogram was 0.74 (95%CI: 0.71-0.76), outperforming ADO, BODE and DOSE risk score.,Besides, the calibration plot of three and five years showed great agreement between nomogram predicted possibility and actual risk.,Decision curve analysis indicated that implementation of the nomogram in clinical practice would be beneficial and better than aforementioned risk scores.,Our new nomogram was a useful tool to assess the probability of severe exacerbations at three and five years for COPD patients and could facilitate clinicians in stratifying patients and providing optimal therapies. | To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD).,Systematic review.,PubMed until November 2018 and hand searched references from eligible articles.,Studies developing, validating, or updating a prediction model in COPD patients and focusing on any potential clinical outcome.,The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD.,The 408 prognostic models were developed in three clinical settings: outpatients (n=239; 59%), patients admitted to hospital (n=155; 38%), and patients attending the emergency department (n=14; 3%).,Among the 408 prognostic models, the most prevalent endpoints were mortality (n=209; 51%), risk for acute exacerbation of COPD (n=42; 10%), and risk for readmission after the index hospital admission (n=36; 9%).,Overall, the most commonly used predictors were age (n=166; 41%), forced expiratory volume in one second (n=85; 21%), sex (n=74; 18%), body mass index (n=66; 16%), and smoking (n=65; 16%).,Of the 408 prognostic models, 100 (25%) were internally validated and 91 (23%) examined the calibration of the developed model.,For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation.,Model discrimination using the C statistic was available for 311 (76%) models. 38 models were externally validated, but in only 12 of these was the validation performed by a fully independent team.,Only seven prognostic models with an overall low risk of bias according to PROBAST were identified.,These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al.,A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769.,This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients.,The findings indicate several methodological pitfalls in their development and a low rate of external validation.,Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies.,PROSPERO CRD42017069247 | 1 |
Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations.,Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.,Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.,Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%).,Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter.,We employed an unsupervised method for clustering.,Four clusters were identified.,Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema.,Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations.,Cluster 4 showed relatively low FEV1/FVC and high exacerbations.,While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters.,Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.,The online version of this article (10.1186/s12931-018-0888-7) contains supplementary material, which is available to authorized users. | Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD.,The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described.,We aimed to assess airway dimensions in COPD subjects with and without BDR.,We analyzed subjects with GOLD 1-4 disease in the COPDGene® study who had CT airway analysis.,We divided patients into two groups: BDR + (post bronchodilator ΔFEV1 ≥ 10%) and BDR-(post bronchodilator ΔFEV1 < 10%).,The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA.,Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter.,%Emphysema and %gas trapping were also calculated.,2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis.,The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group.,In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV1, and %predicted FVC, airway wall measures remained independent predictors of BDR.,Using a threshold change in FEV1 ≥ 15% and FEV1 ≥ 12% and 200 mL to divide patients into groups, the results were similar.,BDR in COPD is independently associated with CT evidence of airway pathology.,This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD. | 1 |
(1) Background: Chronic obstructive pulmonary disease (COPD) is defined as an inflammatory disorder that presents an increasingly prevalent health problem.,Accelerated aging has been examined as a pathologic mechanism of many chronic diseases like COPD.,We examined whether COPD is combined with accelerated aging, studying two hormones, dehydroepiandrosterone (DHEA) and growth hormone (GH), known to be characteristic biological markers of aging.,(2) Methods: Data were collected from 119 participants, 70 (58.8%) COPD patients and 49 (41.2%) from a health control group over the period of 2014-2016 in a spirometry program.,Information about their medical history, tobacco use, and blood tests was obtained.,(3) Results: The average age of the health control patients was 73.5 years (SD = 5.5), and that of the COPD patients was 75.4 years (SD = 6.9).,Both groups were similar in age and sex.,A greater proportion of smokers were found in the COPD group (87.1%) versus the control group (36.7%).,The majority of COPD patients were classified as STAGE II (51.4%) and STAGE III (37.1%) according to GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease).,Levels of DHEA (SD = 17.1) and GH (SD = 0.37) were significantly lower in the COPD group (p < 0.001) compared to those in the controls (SD = 26.3, SD = 0.79).,DHEA and GH were more significant and negatively correlated with age.,The regression equation of DHEA with age produced a coefficient equal to 1.26.,In this study, the difference in DHEA between COPD patients and controls was, on average, 30.2 μg/dL, indicating that the biological age of a COPD patient is on average about 24 years older than that of a control subject of the same age.,Similarly, the difference in GH between COPD patients and controls was, on average, 0.42 ng/mL, indicating that the biological age of a COPD patient is on average about 13.1 years older than that of a control subject of the same age.,(4) Conclusions: The findings of our study strongly suggest the presence of premature biological aging in COPD patients.,Their biological age could actually vary from 13 to 23 years older than non-COPD controls according to DHEA and GH variation. | Supplemental Digital Content is available in the text,This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature.,Literature was searched in several electronic databases.,After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model.,Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients’ data) were used for meta-analysis.,Average age of COPD patients was 66.66 ± 8.72 years of whom 55.4 ± 11.9% were males.,The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls.,COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies. | 1 |
Counseling has been suggested as a promising approach for facilitating changes in health behavior.,The aim of this systematic review of counseling interventions for people with COPD was to describe: 1) counseling definitions, 2) targeted health behaviors, 3) counseling techniques and 4) whether commonalities in counseling techniques were associated with improved health behaviors.,Ten databases were searched for original randomized controlled trials which included adults with COPD, used the term “counseling” as a sole or component of a multifaceted intervention and were published in the previous 10 years.,Data extraction, study appraisal and coding for behavior change techniques (BCTs) were completed by two independent reviewers.,Data were synthesized descriptively, with meta-analysis conducted where possible.,Of the 182 studies reviewed as full-text, 22 were included.,A single study provided a definition for counseling.,Two key behaviors were the main foci of counseling: physical activity (n=9) and smoking cessation (n=8).,Six studies (27%) reported underlying models and/or theoretical frameworks.,Counseling was the sole intervention in 10 studies and part of a multicomponent intervention in 12.,Interventions targeting physical activity included a mean of 6.3 (±3.1) BCTs, smoking cessation 4.9 (±2.9) BCTs and other behaviors 6.5 (±3.9) BCTs.,The most frequent BCTs were social support unspecified (n=22; 100%), goal setting behavior (n=11), problem-solving (n=11) and instructions on how to perform the behavior (n=10).,No studies shared identical BCT profiles.,Counseling had a significant positive effect for smoking cessation and positive but not significant effect for physical activity.,Counseling for health behavior change was rarely defined and effectiveness varied by target behavior.,Provision of specific details when reporting studies of counseling interventions (definition, BCTs, dosage) would allow clarification of the effectiveness of counseling as an approach to health behavior change in people with COPD. | Depression and anxiety are very common in people with chronic obstructive pulmonary disease (COPD) and are associated with excess morbidity and mortality.,Patients prefer non-drug treatments and clinical guidelines promote non-pharmacological interventions as first line therapy for depression and anxiety in people with long term conditions.,However the comparative effectiveness of psychological and lifestyle interventions among COPD patients is not known.,We assessed whether complex psychological and/or lifestyle interventions are effective in reducing symptoms of anxiety and depression in patients with COPD.,We then determined what types of psychological and lifestyle interventions are most effective.,Systematic review of randomised controlled trials of psychological and/or lifestyle interventions for adults with COPD that measured symptoms of depression and/or anxiety.,CENTRAL, Medline, Embase, PsychINFO, CINAHL, ISI Web of Science and Scopus were searched up to April 2012.,Meta-analyses using random effects models were undertaken to estimate the average effect of interventions on depression and anxiety.,Thirty independent comparisons from 29 randomised controlled trials (n = 2063) were included in the meta-analysis.,Overall, psychological and/or lifestyle interventions were associated with small reductions in symptoms of depression (standardised mean difference −0.28, 95% confidence interval −0.41 to −0.14) and anxiety (standardised mean difference −0.23, 95% confidence interval −0.38 to −0.09).,Multi-component exercise training was the only intervention subgroup associated with significant treatment effects for depression (standardised mean difference −0.47, 95% confidence interval −0.66 to −0.28), and for anxiety (standardised mean difference −0.45, 95% confidence interval −0.71 to −0.18).,Complex psychological and/or lifestyle interventions that include an exercise component significantly improve symptoms of depression and anxiety in people with COPD.,Furthermore, multi-component exercise training effectively reduces symptoms of anxiety and depression in all people with COPD regardless of severity of depression or anxiety, highlighting the importance of promoting physical activity in this population. | 1 |
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. | Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients’ quality of life.,This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.,We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups.,Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations.,We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group.,After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33).,Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52).,No differences were found for exacerbations, pulmonary function or exercise capacity.,We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program.,However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified.,ISRCTN94514482 | 1 |
Computed tomography scan images have been used to identify different radiological COPD phenotypes based on the presence and severity of emphysema, bronchial wall thickening, and bronchiectasis.,Bronchiectasis is defined as an abnormal dilation of the bronchi, usually as a result of chronic airway inflammation and/or infection.,The prevalence of bronchiectasis in patients with COPD is high, especially in advanced stages.,The identification of bronchiectasis in COPD has been defined as a different clinical COPD phenotype with greater symptomatic severity, more frequent chronic bronchial infection and exacerbations, and poor prognosis.,A causal association has not yet been proven, but it is biologically plausible that COPD, and particularly the infective and exacerbator COPD phenotypes, could be the cause of bronchiectasis without any other known etiology, beyond any mere association or comorbidity.,The study of the relationship between COPD and bronchiectasis could have important clinical implications, since both diseases have different and complementary therapeutic approaches.,Longitudinal studies are needed to investigate the development of bronchiectasis in COPD, and clinical trials with treatments aimed at reducing bacterial loads should be conducted to investigate their impact on the reduction of exacerbations and improvements in the long-term evolution of the disease. | Pneumonia poses a significant risk in patients with moderate to severe chronic obstructive pulmonary disease but data are limited on the disease phenotypes most susceptible to pneumonia.,Cluster analysis using a data-driven recursive partitioning algorithm was employed using baseline data from two pooled one-year randomized exacerbation trials (n=3,255) of fluticasone furoate/vilanterol or vilanterol alone to identify distinct patient groups at greatest risk of pneumonia or serious (hospitalization or death) pneumonia.,Five clusters were identified.,Patients at greater risk of first pneumonia had more severe obstruction (forced expiratory volume in one second/forced vital capacity <46%) and either a body mass index <19 kg/m2 (hazard ratio 7.8, 95% confidence interval 4.7-13.0; n=144) or a pneumonia history and greater comorbidities (hazard ratio 4.8, 95% confidence interval 3.0-7.7; n=374) relative to the cluster with the lowest pneumonia risk (reference; n=1310).,Multiple comorbidities and use of psychoanaleptics also contributed to an increased risk of pneumonia in more obstructed patients.,Independent of cluster, use of inhaled corticosteroids was associated with pneumonia (hazard ratio 1.89, 95% confidence interval 1.25-2.84) and serious pneumonia (hazard ratio 2.92, 95% confidence interval 1.40-6.01).,Cluster analysis can identify patient populations at risk for serious safety outcomes and inform risk management strategies to optimize patient management.,The greatest risk for pneumonia was in subjects with multiple pneumonia risk factors. | 1 |
Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD.,During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear.,Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts.,This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation.,Multi-center study of four academic healthcare institutions.,Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation.,Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data.,Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations.,There was an almost perfect agreement for acceptability (κ = 0.92) and reproducibility (κ =0.93) of spirometry tracings.,Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality.,Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease.,Obese patients (BMI ≥30 kg/m2) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007).,Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation.,Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients. | To assess whether spirometry done in hospital during an admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is clinically useful for long-term management.,Patients admitted to hospital with a clinical diagnosis of AECOPD had spirometry post-bronchodilator at discharge and approximately 4 weeks later.,Spirometry was achieved in less than half of those considered to have AECOPD.,Of 49 patients who had spirometry on both occasions, 41 met the GOLD criteria for COPD at discharge and 39 of these met the criteria at 1 month.,For the 41, spirometry was not statistically different between discharge and 1 month but often crossed arbitrary boundaries for classification of severity based on FEV1.,The eight who did not meet GOLD criteria at discharge were either misclassified due to comorbidities that reduce FVC, or they did not have COPD as a cause of their hospital admission.,Spirometry done in hospital at the time of AECOP is useful in patients with a high pre-test probability of moderate-to-severe COPD.,Small changes in spirometry at 1 month could place them up or down one grade of severity.,Spirometry at discharge may be useful to detect those who warrant further investigation. | 1 |
Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients. | 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 |
Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear.,This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD.,Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers.,Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay.,Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test.,Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD.,First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007).,Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25-75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively).,Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1.,Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD. | Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems.,Innovative sampling techniques have led to the identification of several pulmonary biomarkers.,Although some molecules are promising, their usefulness in clinical practice is not yet established.,Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD.,We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method.,Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further.,Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment.,According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels.,Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis.,Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited.,In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes.,However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use.,Clinical trials that incorporate biomarkers in decisional algorithms are required. | 1 |
In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.,Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint.,Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment.,A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.,In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators.,Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses.,Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers.,The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.,The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.,NCT00563381; Study identifier: BI 205.389. | 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 |
We aimed to investigate (1) the relationship between cognitive impairment (CI) and disease severity and (2) the potential differences in exercise performance, daily activities, health status, and psychological well-being between patients with and without CI.,Clinically stable chronic obstructive pulmonary disease (COPD) patients, referred for pulmonary rehabilitation, underwent a neuropsychological examination.,Functional exercise capacity (6-minute walk test [6MWT]), daily activities (Canadian Occupational Performance Measure [COPM]), health status (COPD Assessment Test [CAT]) and St George’s Respiratory Questionnaire-COPD specific [SGRQ-C]), and psychological well-being (Hospital Anxiety and Depression Scale [HADS], Beck Depression Inventory [BDI], and Symptom Checklist 90 [SCL-90]) were compared between patients with and without CI.,Of 183 COPD patients (mean age 63.6 (9.4) years, FEV1 54.8 (23.0%) predicted), 76 (41.5%) patients had CI.,The prevalence was comparable across Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 (44.8%, 40.0%, 41.0%, 43.5%, respectively, p = 0.97) and GOLD groups A-D (50.0%, 44.7%, 33.3%, 40.2%, respectively, p = 0.91).,Patients with and without CI were comparable for demographics, smoking status, FEV1% predicted, mMRC, 6MWT, COPM, CAT, HADS, BDI, and SCL-90 scores.,Clinical characteristics of COPD patients with and without CI are comparable.,Assessment of CI in COPD, thus, requires an active case-finding approach. | Depression is a common comorbidity among patients with Chronic Obstructive Pulmonary Disease (COPD) and has a significant impact on the course of the disease.,The aim of this study is to determine association between COPD Assessment Test (CAT) and major depression among clinically stable out-patient COPD subjects with mild hypoxemia.,Case-control study.,Cases were 30 patients with major depression and controls were 30 patients without depression.,Major depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria by a psychiatric evaluation.,All possible predictive variables were included in a multivariate logistic regression model to assess the association between major depression and each independent variable, while controlling for the sleep parameters.,CAT score >20 was associated with major depression (OR 7.88; 95% CI 1.96 - 31.7; p = 0.004).,CAT score >20 was associated with major depression, suggesting CAT as a predictor variable of major depression among COPD patients with mild hypoxemia, and indicating that an additional specific evaluation for the presence of major depression should be done. | 1 |
Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men.,However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades.,This has largely been attributed to historical increases in tobacco consumption among women.,But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy.,Interestingly, nonsmokers with COPD are more likely to be women.,In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations.,Women historically have had lower mortality with COPD, but this is changing as well.,There are also differences in how men and women respond to different therapies.,Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women.,In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research. | Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. | 1 |
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. | Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | 1 |
This study aims to compare demographic and clinical characteristics of chronic obstructive pulmonary disease (COPD) patients who complete and fail to complete outpatient pulmonary rehabilitation (PR) program and to determine the reasons for not completing the program.,Patients with COPD referred to the PR program were divided into two groups: Those who completed the program were classified as group 1 and those who did not complete were classified as group 2, and their data were compared.,Patients who failed to complete the program were contacted through phone and asked why they ceased their participation in the program.,In group 2, number of smoker patients and patients using nebulizer and receiving long-term oxygen treatment, emergency admissions, and dyspnea perception were higher (p = 0.003, p < 0.001, p = 0.033, p = 0.011, p < 0.001, respectively); forced expiratory volume in one second (%) value, exercise capacity, and quality of life were lower (p = 0.024, p = 0.001, p = 0.014, respectively).,When considered from the sociodemographic perspective, group 2 had a lower education level and a higher rate of living alone (p < 0.001).,Factors impairing the program compliance were lack of motivation (49.0%), transportation problems (23.8%), COPD exacerbation (18.4%), work-related reasons (4.8%), and hospitalization (4.1%), respectively.,Smokers and severe COPD patients fail to complete PR program due to various reasons, especially lack of motivation.,It is very important for health practitioners to inform patients accurately and adopt a positive attitude. | The St.,George’s Respiratory Questionnaire (SGRQ) and chronic obstructive pulmonary disease (COPD) assessment test (CAT) are the measures used to assess health status.,This study aims to examine the responsiveness of these tools by severity of dyspnoea category in patients with COPD.,Forty-nine COPD patients who underwent a 12-week pulmonary rehabilitation (PR) programme were assessed at baseline, 12 weeks and at 28-week follow-up.,Patients were categorized into two groups by severity of dyspnoea category (i.e. mild to moderate (modified Medical Research Council (mMRC) 1-2) and severe to very severe (mMRC 3-4)) using the mMRC dyspnoea scale.,Effect size (ES) was computed as estimates of responsiveness.,The SGRQ demonstrated greater responsiveness by total sample (SGRQ, ES = 0.87; CAT, ES = 0.75) and for the mMRC 3-4 category (SGRQ, ES = 0.91; CAT, ES = 0.76) on completion of PR.,At 28-week follow-up, overall comparable responsiveness of the CAT and SGRQ was identified by total sample (SGRQ, ES = 0.75; CAT, ES = 0.74) and by severity of dyspnoea category.,The symptom, impact and activity domains of the SGRQ showed good responsiveness, with greater ESs obtained overall for the mMRC 3-4 category.,On completion of PR, the SGRQ demonstrates a greater responsiveness with COPD patients, especially in relation to the mMRC 3-4 category, while both the CAT and SGRQ show comparable responsiveness on follow-up. | 1 |
Glycopyrronium bromide (NVA237) is an inhaled long-acting muscarinic antagonist in development for treatment of COPD.,This study compared the efficacy and safety of once-daily (OD) and twice-daily (BID) glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD.,Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design.,Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and <80% predicted, FEV1/FVC <0.7) were randomized to one of 16 independent sequences for 28 days.,Primary endpoint: mean trough FEV1 at Day 28.,385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted) were randomized; 88.6% completed.,All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD) to 160 mL (glycopyrronium bromide 50 μg BID).,Pharmacodynamic steady-state was reached by Day 7.,There was a small separation (≤37 mL) between BID and OD dose-response curves for mean trough FEV1 at steady-state in favour of BID dosing.,Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL).,Dose-response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12-24 hours.,The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL).,Glycopyrronium bromide was safe and well tolerated at all doses.,Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period, and in terms of FEV1 AUC0-24h is not significantly different than the same total daily dose administered BID.,Importantly, OD dosing may confer better patient adherence.,The results are consistent with previous glycopyrronium bromide studies and support once-daily dosing of glycopyrronium bromide 50 μg in patients with moderate-to-severe COPD.,ClinicalTrials.gov: NCT01119950 | 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 authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate.,Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis.,Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided. | Randomized controlled trials have confirmed the evidence and helped to define when and where non invasive mechanical ventilation (NIV) should be the first line treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Noninvasive ventilation has its best indication in moderate-to-severe respiratory acidosis in patients with AECOPD.,For this indication, studies conducted in ICU, in wards and in accident and emergency departments confirmed its effectiveness in preventing endotracheal intubation and reducing mortality.,The skill of the health care team promotes proper NIV utilization and improves the patient outcome.,Patients with severe acidosis or with altered levels of consciousness due to hypercapnic acute respiratory failure are exposed to high risk of NIV failure.,In these patients a NIV trial may be attempted in closely monitored clinical settings where prompt endotracheal intubation may be assured. | 1 |
The term Asthma and COPD Overlap (ACO) describes a condition where asthma and COPD overlap.,We aimed to investigate associations between ACO and insomnia and respiratory symptoms, and to investigate the prevalence of ACO and the characteristics of subjects with ACO in two Northern European population studies.,The study comprised 25 429 subjects aged ≥ 40 years who participated in one of two Northern European general population surveys.,Both surveys included questions on asthma, COPD, respiratory and sleep-related symptoms, including difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, and excessive daytime sleepiness.,ACO was defined as having both self-reported asthma and COPD.,The prevalence of ACO was 1.0%.,The group with ACO had a higher prevalence of both insomnia and respiratory symptoms than subjects with only asthma or COPD.,Having ACO was independently associated with a 2-3 times higher probability of having sleep-related symptoms as compared with the group without asthma or COPD, after adjustment for age, sex, BMI, smoking history and educational level (adjusted odds ratio 2.14-3.36, 95% CI).,Subjects with ACO have a high prevalence of insomnia and respiratory symptoms.,To our knowledge, this is the first study to assess the association between sleep-related symptoms and ACO. | To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data.,Primary care; Lothian (population approximately 800 000), Scotland.,Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record.,Patients were followed up until 2010, death or they left a participating practice.,First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care.,1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission.,Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model.,More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model.,High BMI was associated with a lower risk of first AECOPD admission and readmission.,Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission.,Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission.,The study highlights the important role of primary care in preventing or delaying a first AECOPD admission. | 1 |
Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level.,We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple therapy in sputum cells and whole blood of patients with COPD and chronic bronchitis.,Whole genome gene expression analysis was carried out by microarray in 54 patients before and after 32 days treatment with CHF6001 800 and 1600 μg and placebo twice daily (BID) in a randomised crossover study.,CHF6001 had a strong effect in sputum, with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-adjusted for False Discovery Rate < 0.05) with 800 and 1600 μg BID, respectively.,Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors.,A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (> 87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumour necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14.,The effect in blood was not significant.,Inhaled PDE4 inhibition by CHF6001 on top of triple therapy in patients with COPD and chronic bronchitis significantly modulated key inflammatory targets and pathways in the lung but not in blood.,Mechanistically these findings support a targeted effect in the lung while minimising unwanted systemic class-effects.,ClinicalTrial.gov, EudraCT, 2015-005550-35.,Registered 15 July 2016. | Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS).,We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.,The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone.,Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George’s Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).,In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts.,In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm.,In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm.,Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies.,ICS/LABA led to greater improvements in St George’s Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.,Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction.,Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations. | 1 |
Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease.,To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT).,Qualitative: patient focus group and interviews to address content validity.,Quantitative: secondary data analyses to test reliability and validity.,Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male.,Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure.,Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male.,Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score.,Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively.,Validity: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms).,RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05).,E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001).,Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD.,Further study of sensitivity to change is warranted. | 1 |
Introduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD.,Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.,Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017.,Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.,Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events).,In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively).,In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%.,Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events.,Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment. | 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 |
Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD).,It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD).,However, little is known about which phenotypes of COPD are associated with increased EAT.,One hundred and eighty smokers who were referred to the clinic were consecutively enrolled.,A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT.,These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively.,The same measurements were made on 225 Vietnamese COPD patients to replicate the results.,Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70.,The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients.,The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001).,These results were replicated in the Vietnamese population.,The EAT area is independently associated with airway wall thickness.,Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. | New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD). | 1 |
The objective of this study was to determine if gene-environment interactions between cigarette smoking and interleukin-6 (IL6), interferon-γ (IFNG), interleukin-1β (IL1B), or interleukin-1 receptor antagonist (IL1RN) single nucleotide polymorphisms are associated with lung function decline and cardiovascular disease in chronic obstructive pulmonary disease (COPD).,Single nucleotide polymorphisms (SNPs) in IL6, IFNG, IL1B, and IL1RN were genotyped in the Lung Health Study and correlated with rate of decline of forced expiratory volume in 1 second (FEV1) over 5 years, baseline FEV1, serum protein levels, cardiovascular disease, and interactions with smoking.,The IL6 rs2069825 single nucleotide polymorphism was associated with the rate of decline of prebronchodilator FEV1 (P = 0.049), and was found to have a significant interaction (P = 0.004) with mean number of cigarettes smoked per day.,There was also a significant interaction of IFNG rs2069727 with smoking on prebronchodilator (P = 0.008) and postbronchodilator (P =0.01) FEV1.,The IL6 polymorphism was also associated with cardiovascular disease in heterozygous individuals (P = 0.044), and was found to have a significant interaction with smoking (P = 0.024).,None of the genetic variants were associated with their respective serum protein levels.,The results suggest interactions of IL6 rs2069825 and IFNG rs2069727 single nucleotide polymorphisms with cigarette smoking on measures of lung function.,The IL6 rs2069825 single nucleotide polymorphism also interacted with smoking to affect the risk of cardiovascular disease in COPD patients. | A growing body of evidence indicates that matrix metalloproteinases (MMPs) play a role in the pathogenesis of COPD.,Therefore, we conducted a candidate gene association study of 4 promoter polymorphisms that are known to modify expression levels of the MMP-1, MMP-2, and MMP-9 genes and a Gln279Arg polymorphism in exon 6 of MMP-9 that modifies the substrate-binding region.,We examined the association of each variant and haplotypes in 385 male veterans with greater than 20 pack-years of cigarette smoking whose COPD status was characterized using spirometry.,The association of these polymorphisms was also examined with decline of pulmonary function in a subset of participants.,Only the 279Arg variant was more common in participants with COPD and the homozygous variant was associated with a 3-fold increased risk for COPD.,In the haplotype analysis, the haplotype comprising the 249Arg and the CA promoter polymorphism within the MMP-9 gene was associated with risk, suggesting that either 279Arg or a linked variant on this haplotype underlies the association.,No association of this polymorphism was found with decline in pulmonary function.,These studies show that variants of the MMP-9 gene are associated with COPD in this cohort of veterans. | 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. | Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).,Design Population based longitudinal consecutive cohort study.,Setting Centres prescribing long term oxygen therapy in Sweden.,Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.,Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.,Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation.,No patient was lost to follow-up.,Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively.,Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend.,Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44).,Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99).,Associations were not modified by being naive to the drugs or by hypercapnia.,Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease. | 1 |
The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR).,However, despite its benefits, the outcome of ELVR remains difficult to predict.,We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy.,Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves.,Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline.,The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI).,These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up.,Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001).,TL perfusion was not associated with changes in the outcome.,High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012).,Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001).,This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR.,Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. | Diaphragmatic dysfunction is an important reason for dyspnea in COPD patients.,But diaphragmatic dysfunction is difficult to evaluate.,Ultrasound is an option.,We measure sonographically the up- and downward movement of the lung silhouette on both hemidiaphragms.,The aim of this prospective investigation was to compare this method with another sonographic method that visualizes the right hemidiaphragm directly and to compare the sonographic results with lung function parameters.,Eighty participants - 20 healthy persons and 60 COPD patients - three groups each with 20 patients with COPD GOLD II, III, and IV - were investigated.,The sonographic measurements of the diaphragms were performed.,Lung function parameters, blood gases, and 6-minute walk test were also collected and compared to the sonographic results.,The sonographic measurement of the lung silhouette was easy to perform in all study participants.,The correlation between the sonographic methods measuring the right hemidiaphragmatic movement was strong (r=0.85).,There was also a strong correlation between the demonstrated sonographic measurement of the up- and downward movement of the lung silhouette and the forced expiratory volume in the first second (r=0.83).,We demonstrated that the sonographic measurement of the movement of the lung silhouette is an easy way to establish diaphragmatic dysfunction in COPD patients; it can be done in all patients with reliable results for the right and the left hemidiaphragm. | 1 |
Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases.,The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid.,An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid).,The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population.,Patients were deemed to have COPD if this diagnosis appeared on their clinical histories.,Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated.,Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%).,After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity.,Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs. | Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain. | 1 |
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity.,Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however.,Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients.,To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure.,BAL fluid and lung tissue were collected after the final exposure.,Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography.,HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays.,MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels.,MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice.,BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR.,Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR.,MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR.,Inhibition of MIF may provide a novel anti-inflammatory approach in COPD. | There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid.,A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed.,The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements.,Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals.,If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke.,Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults.,This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD. | 1 |
This study aimed to investigate whether perioperative inhalations of long-acting beta-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) might decrease the incidence of postoperative complications in lung cancer patients with chronic obstructive pulmonary disease (COPD).,We retrospectively analyzed 108 patients with COPD who underwent pulmonary resections for primary lung cancer at our hospital between January 2013 and January 2016 to determine the association between the incidence of postoperative complications (e.g., prolonged air leakage and pneumonia) and the use of LABAs or LAMAs.,Thirty patients with COPD experienced postoperative complications (27.8%): Fourteen patients had prolonged air leakages (more than 7 days), ten patients developed pneumonia.,The frequency of these postoperative pulmonary complications was significantly higher among the patients with COPD (24/108 cases, 22.2%), compared with the frequency among non-COPD patients (15/224 cases, 6.7%).,Inhaled bronchodilators, such as LAMA or LABA, were prescribed for 34 of the 108 patients with COPD; the remaining 74 patients were not treated with bronchodilators.,Pulmonary complications were significant lower among the LAMA or LABA users (3/34 cases, 8.8%) than among the untreated COPD patients (21/74 cases, 28.4%).,For lung cancer patients with COPD, preoperative management using LABA or LAMA bronchodilators and smoking cessation can reduce the frequency of postoperative pulmonary complications after surgical lung resection.,LAMA or LABA inhalation might be useful for not only perioperative care, but also for the long-term survival of COPD patients after surgery. | Previous studies have relied on international spirometry criteria to diagnose COPD in patients with lung cancer without considering the effect lung cancer might have on spirometric results.,The aim of this study was to examine the prevalence of COPD and emphysema at the time of primary lung cancer diagnosis and to examine factors associated with survival.,Medical records, pulmonary function tests, and computed tomography scans were used to determine the presence of COPD and emphysema in patients diagnosed with primary lung cancer at the University Hospital of North Norway in 2008-2010.,Among the 174 lung cancer patients, 69% had COPD or emphysema (39% with COPD, 59% with emphysema; male:female ratio 101:73).,Neither COPD nor emphysema were significantly associated with lung cancer mortality, whereas patients with non-small-cell lung cancer other than adenocarcinoma and squamous cell carcinoma had a risk of lung cancer mortality that was more than four times higher than that of patients with small-cell lung cancer (hazard ratio [HR] 4.19, 95% confidence interval [CI] 1.56-11.25).,Females had a lower risk of lung cancer mortality than males (HR 0.63, 95% CI 0.42-0.94), and patients aged ≥75 years had a risk that was twice that of patients aged <75 years (HR 2.48, 95% CI 1.59-3.87).,Low partial arterial oxygen pressure (4.0-8.4 kPa) increased the risk of lung cancer mortality (HR 2.26, 95% CI 1.29-3.96).,So did low partial arterial carbon dioxide pressure (3.0-4.9 kPa) among stage IV lung cancer patients (HR 2.23, 95% CI 1.29-3.85).,Several patients with respiratory failure had previously been diagnosed with COPD.,The observed prevalence of COPD was lower than that in previous studies.,Neither COPD nor emphysema were significantly associated with lung cancer mortality. | 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. | Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | 1 |
The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO2) for 60 days.,Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO2 to stabilize mast cell membranes.,The second group (control) was not treated.,Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation.,Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats.,The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats.,Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats.,This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons. | In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction.,In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown.,We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.,Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase.,Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.,COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls.,In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02).,Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.,More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients.,It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered. | 1 |
Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations.,The AUDIPOC is a Spanish nationwide clinical audit that identified large between‐hospital variations in care and clinical outcomes.,Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so‐called hospital‐clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted.,A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90‐day follow‐up.,Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes.,For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient‐ and hospital‐level covariables.,The hospital‐clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR).,In the empty models, the ICC (MOR) for inpatient mortality and the follow‐up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively.,In the adjusted models, the variables that most represented the patients’ clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations.,By contrast, the resource factors were primarily unrelated with outcomes.,This study demonstrates a noteworthy reduction in the observed crude between‐hospital variation in outcomes after accounting for the hospital‐cluster effect and the variables representing patient's clinical conditions.,This emphasises the predictor importance of the patients’ clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
Telerehabilitation (TR) aimed at patients with COPD has shown promising effects on symptoms, physical function, and quality of life, but little research has been conducted to understand the impact of implementation on frontline health professionals.,Therefore, the aim of this study was to examine the barriers and enablers of health professionals to online exercise-based TR in patients with COPD, to support a successful implementation process.,Semistructured individual and focus group interviews were conducted with 25 health professionals working with conventional COPD rehabilitation or TR.,Interviews were audio-taped and transcribed verbatim.,Investigator triangulation was applied during data generation.,The Theoretical Domains Framework directed the interview guide and was used as a coding framework in the analysis.,We identified six predominant domains essential in understanding the enablers and barriers of TR from a staff perspective: 1) skills, 2) professional role and identity, 3) beliefs about capabilities, 4) beliefs about consequences, 5) environmental context and resources, and 6) social influences.,We found that health professionals held both enablers and barriers important for the implementation process of TR.,TR introduces new work tasks and new ways for the health professionals to communicate and exercise with the patients, which influence their professional role and self-perceived capability.,Specific attention toward involvement of the health professionals in the decision process combined with sufficient education and skill training is highly essential to support a successful implementation of TR in clinical practice. | Pulmonary rehabilitation is known to improve function and quality of life for people with chronic obstructive pulmonary disease (COPD).,However, little research has been conducted on the influence of culture on experiences of pulmonary rehabilitation.,This study examined factors influencing uptake of pulmonary rehabilitation by Māori with COPD in New Zealand.,Grounded theory nested within kaupapa Māori methodology.,Transcripts were analyzed from interviews and focus groups with 15 Māori and ten New Zealand non-Māori invited to attend pulmonary rehabilitation for COPD.,Māori participants had either attended a mainstream hospital-based program, a community-based program designed “by Māori, for Māori”, or had experienced both.,Several factors influencing uptake of pulmonary rehabilitation were common to all participants regardless of ethnicity: 1) participants’ past experiences (eg, of exercise; of health care systems), 2) attitudes and expectations, 3) access issues (eg, time, transport, and conflicting responsibilities), and 4) initial program experiences.,These factors were moderated by the involvement of family and peers, interactions with health professionals, the way information on programs was presented, and by new illness events.,For Māori, however, several additional factors were also identified relating to cultural experiences of pulmonary rehabilitation.,In particular, Māori participants placed high value on whakawhanaungatanga: the making of culturally meaningful connections with others.,Culturally appropriate communication and relationship building was deemed so important by some Māori participants that when it was absent, they felt strongly discouraged to attend pulmonary rehabilitation.,Only the more holistic services offered a program in which they felt culturally safe and to which they were willing to return for ongoing rehabilitation.,Lack of attention to cultural factors in the delivery of pulmonary rehabilitation may be a barrier to its uptake by indigenous, minority ethnic groups, such as New Zealand Māori.,Indigenous-led or culturally responsive health care interventions for COPD may provide a solution to this issue. | 1 |
Nasal high-flow oxygen therapy (HFOT) is a novel treatment option for patients suffering from acute or chronic respiratory failure.,Aim of our study was to compare safety and efficacy of HFOT with those of conventional oxygen treatment (COT) in normo- and hypercapnic COPD patients.,A single cohort of 77 clinically stable hypoxemic patients with an indication for long-term oxygen treatment (LTOT) with or without hypercapnia successively received COT and HFOT for 60 min each, including oxygen adaption and separated by a 30 min washout phase.,HFOT was well-tolerated in all patients.,A significant decrease in PaCO2 was observed during oxygen adaption of HFOT, and increased PaO2 coincided with significantly increased SpO2 and decreased AaDO2 during both treatment phases.,Even at a flow rate of 15 L/min, oxygen requirement delivered as air mixture by HFOT tended to be lower than that of COT (2.2 L/min).,Not only was no increase in static or dynamic lung volumes observed during HFOT, but even was a significant reduction of residual lung volume measured in 36 patients (28%).,Thus, short-term use of HFOT is safe in both normocapnic and hypercapnic COPD patients.,Lower oxygen levels were effective in correcting hypoxemic respiratory failure and reducing hypercapnia, leading to a reduced amount of oxygen consumption.,Long-term studies are needed to assess safety, tolerability, and clinical efficacy of HFOT.,ClinicalTrials.gov NCT01686893 13.09.2012 retrospectively registered (STIT-1) and NCT01693146 14.09.2012 retrospectively registered (STIT-2).,Studies were approved by the local ethics committee (Ethikkommission der Medizinischen Universität Innsbruck, Studienkennzahl UN3547, Sitzungsnummer 274/4.19). | The use of noninvasive intermittent positive pressure ventilation (NIPPV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking.,The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation (NIPPV + PR) with rehabilitation alone (PR) in COPD patients with chronic hypercapnic respiratory failure.,Sixty-six patients could be analyzed for the two-year home-based follow-up period.,Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a random effect on the intercept, and adjustment for baseline values.,The primary outcome was health-related quality of life (HRQoL); secondary outcomes were mood state, dyspnea, gas exchange, functional status, pulmonary function, and exacerbation frequency.,Although the addition of NIPPV did not significantly improve the Chronic Respiratory Questionnaire compared to rehabilitation alone (mean difference in change between groups -1.3 points (95% CI: -9.7 to 7.4)), the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure questionnaire (-13.4% (-22.7 to -4.2; p = 0.005)), mood state (Hospital Anxiety and Depression scale -4.0 points (-7.8 to 0.0; p = 0.05)), dyspnea (Medical Research Council -0.4 points (-0.8 to -0.0; p = 0.05)), daytime arterial blood gases (PaCO2 -0.4 kPa (-0.8 to -0.2; p = 0.01); PaO2 0.8 kPa (0.0 to 1.5; p = 0.03)), 6-minute walking distance (77.3 m (46.4 to 108.0; p < 0.001)), Groningen Activity and Restriction scale (-3.8 points (-7.4 to -0.4; p = 0.03)), and forced expiratory volume in 1 second (115 ml (19 to 211; p = 0.019)).,Exacerbation frequency was not changed.,The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL, mood, dyspnea, gas exchange, exercise tolerance and lung function decline.,The benefits increase further with time.,ClinicalTrials.Gov (ID NCT00135538). | 1 |
The burden of chronic obstructive pulmonary disease (COPD) is high.,Health benefits can be gained in primary care by early detection and preventive measures.,To compare the effectiveness of two strategies for population-based early detection of COPD, taking into account different socioeconomic status (SES) settings.,Practices were randomised on strategy and stratified on SES setting.,The Respiratory Health Screening Questionnaire (RHSQ) was distributed to all participants.,In the practice-managed condition, the practice was responsible for the whole procedure, while in the patient-managed condition, patients were responsible for calculating their RHSQ risk score and applying for a spirometry test.,The main outcome measure was the rate of COPD diagnoses after screening.,More new COPD patients were detected in the practice-managed condition (36%) than in the patient-managed condition (18%).,In low SES practices, more high-risk patients were found (16%) than in moderate-to-high SES practices (9%).,Recalculated for a standard Dutch practice (2,350 patients), the yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.,The practice-managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practices. | More than two-fifths of the world’s population uses solid fuels, mostly biomass, for cooking.,The resulting biomass smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD) among women in developing countries.,To assess whether lower woodsmoke exposure from use of a stove with a chimney, compared to open fires, is associated with lower markers of airway inflammation in young women.,We carried out a cross-sectional analysis on a sub-cohort of participants enrolled in a randomized controlled trial in rural Guatemala, RESPIRE.,We recruited 45 indigenous women at the end of the 18-month trial; 19 women who had been using the chimney stove for 18-24 months and 26 women still using open fires.,We obtained spirometry and induced sputum for cell counts, gene expression of IL-8, TNF-α, MMP-9 and 12, and protein concentrations of IL-8, myeloperoxidase and fibronectin.,Exhaled carbon monoxide (CO) and 48-hr personal CO tubes were measured to assess smoke exposure.,MMP-9 gene expression was significantly lower in women using chimney stoves.,Higher exhaled CO concentrations were significantly associated with higher gene expression of IL-8, TNF-α, and MMP-9.,Higher 48-hr personal CO concentrations were associated with higher gene expression of IL-8, TNF- α, MMP-9 and MMP-12; reaching statistical significance for MMP-9 and MMP-12.,Compared to using an open wood fire for cooking, use of a chimney stove was associated with lower gene expression of MMP-9, a potential mediator of airway remodeling.,Among all participants, indoor biomass smoke exposure was associated with higher gene expression of multiple mediators of airway inflammation and remodeling; these mechanisms may explain some of the observed association between prolonged biomass smoke exposure and COPD. | 1 |
Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments.,In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression.,The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology.,The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription.,Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression).,However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling.,Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD.,Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression.,This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD. | Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease.,In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer.,High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules).,Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.,114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study.,Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ −950 HU, ≤ − 910 HU and mean lung attenuation at the 15th percentile on lung attenuation curve (LP15A).,Multiple regression analysis was performed to determine plasma biomarkers associated with emphysema independent of covariates age, gender, smoking status, body mass index and FEV1.,The findings were subsequently validated using baseline blood samples from a separate cohort of 388 subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA) study.,Regression analysis identified multiple biomarkers associated with CT-assessed emphysema in COPDGene, including advanced glycosylation end-products receptor (AGER or RAGE, p < 0.001), intercellular adhesion molecule 1 (ICAM, p < 0.001), and chemokine ligand 20 (CCL20, p < 0.001).,Validation in the TESRA cohort revealed significant associations with RAGE, ICAM1, and CCL20 with radiologic emphysema (p < 0.001 after meta-analysis).,Other biomarkers that were associated with emphysema include CDH1, CDH 13 and SERPINA7, but were not available for validation in the TESRA study.,Receiver operating characteristics analysis demonstrated a benefit of adding a biomarker panel to clinical covariates for detecting emphysema, especially in those without severe airflow limitation (AUC 0.85).,Our findings, suggest that a panel of blood biomarkers including sRAGE, ICAM1 and CCL20 may serve as a useful surrogate measure of emphysema, and when combined with clinical covariates, may be useful clinically in predicting the presence of emphysema compared to just using covariates alone, especially in those with less severe COPD.,Ultimately biomarkers may shed light on disease pathogenesis, providing targets for new treatments.,The online version of this article (doi:10.1186/s12931-014-0127-9) contains supplementary material, which is available to authorized users. | 1 |
SARS-CoV-2 has restricted access to face-to-face delivery of pulmonary rehabilitation (PR).,Evidence suggests that telehealth-PR is non-inferior to outpatient PR.,However, it is unknown whether patients who have been referred to face-to-face programmes can feasibly complete an online-PR programme.,This service evaluation used a mixed-methods approach to investigate a rapid PR service remodelling using the University of Gloucestershire eLearn Moodle platform.,Quantitative baseline demographic and PR outcome data were collected from online-PR participants, and semistructured interviews were completed with PR staff and participants.,Twenty-five individuals were eligible from a PR waiting list.,Thirteen declined participation and 14 completed PR.,Significant pre-post online PR improvements were achieved in 1 min sit-to-stand (CI 2.1 to 9 (p=0.004)), Generalised Anxiety Disorder (CI −0.3 to −2.6 (p=0.023)), Primary Health Questionnaire-9 (CI −0.3 to −5.1 (p=0.029)), Chronic Respiratory Questionnaire dyspnoea (CI 0.5 to 1.3 (p=0.001)), fatigue (CI 0.7 to 2 (p=0.0004)), emotion (CI 0.7 to 1.7 (p=0.0002)), mastery (CI 0.4 to 1.3 (p=0.001)).,Interviews indicated that patient PR inclusion was made possible with digital support and a PR introduction session improved participant engagement and safety.,Incremental progression of exercise was perceived as more successful online compared with face-to-face PR.,However, perceptions were that education sessions were less successful.,Online-PR required significant staff time resource.,Online-PR improves patient outcomes and is feasible and acceptable for individuals referred for face-to-face PR in the context of a requirement for social distancing.,Face-to-face programmes can be adapted in a rapid fashion with both staff and participants perceiving benefit.,Future pragmatic trials are now warranted comparing online-PR including remote assessments to centre-based PR with suitably matched outcomes, and patient and staff perceptions sought regarding barriers and facilitators of online delivery. | Increasing physical activity (PA) is considered to be an important factor for the efficient management of chronic obstructive pulmonary disease (COPD).,Successful methods required to achieve improvements in PA following pulmonary rehabilitation (PR), however, are rarely reported.,Therefore, we will conduct this trial to evaluate the effectiveness of using a COPD management program delivered to the patient via the KAIA COPD app, a mobile medical application, after the completion of PR.,This is the protocol for a randomized, controlled, open-label, multicentered trial that will be carried out at inpatient PR hospital centers in Germany and Switzerland.,The interventions will involve the use of the KAIA COPD app program (Arm 1) or an active comparator, i.e., usual care (Arm 2).,Patients completing an in-hospital PR program and consenting to participate in the study will be screened with the inclusion and exclusion criteria and enrolled in the study.,After fulfilling the screening requirements, the patients will be randomized into one of the two arms with parallel group assignment in a 1:1 ratio.,The training program will be delivered to the participants grouped in Arm 1 via the KAIA COPD app and to participants grouped in Arm 2 via the regular recommendations or standard of care by the PI.,In total, 104 participants will be included in the trial.,The treatment period will last for 24 weeks.,Electronic versions of questionnaires will be used to collect patient-reported assessments remotely.,The primary outcome measure is the change in physical activity of the intervention group in comparison to the control group, measured over 1 week as the mean steps per day with a Polar A 370 activity tracker, from baseline (end of PR) to the 6-month follow-up.,The secondary outcome measures are functional exercise capacity, health status, sleep quality, exacerbation rate, and depression and anxiety symptoms assessed at several intervals.,This study seeks to prove the effects of the KAIA COPD mobile application in COPD patients after PR.,The app offers educational, exercise training plus activity monitoring and motivational programs that can be easily implemented in the patient’s home setting, enabling patients to maintain the effects that are typically elicited in the short term after pulmonary rehabilitation for the long term.,German Clinical Trials Register (DRKS00017275).,Protocol version 2.0 dated 3 June 2019. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting.,All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database.,From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected.,Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD.,Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort.,Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively).,The majority of patients in these groups were not receiving maintenance treatment.,The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis. | 1 |
There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov | 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 |
Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | Little information is available regarding the vulnerability of patients with chronic obstructive pulmonary disease (COPD) in China.,We aimed to assess this according to patient gender.,A cross-sectional study was conducted in the rural area of Xuzhou in China.,We interviewed and administered questionnaires to 2825 male and 2825 female patients with COPD and subjected the data generated to statistical analysis.,We compared differences between proportions of male and female patients using the χ2 test.,The rate of current smoking in men was 30.1%, whereas that in women was 10.9%, and 31.5% of men had a history of using biomass fuel compared with 75.3% of women.,Further, 26.0% of the male patients and 16.4% of the female patients did not take theophylline regularly when their disease was stable.,During acute exacerbations, 65.8% of the male patients and 39.7% of the female patients took theophylline or similar drugs.,The average potential shortening of life expectancy was 1.76 years for men and 1.18 years for women.,The average indirect economic burden was 11158.4 yuan for men and 7481.2 yuan for women.,The quality of life was worse in female patients than in male patients.,We found that patients with COPD were vulnerable and that factors determining vulnerability were different for men than for women.,Therefore, we recommend adopting different measures for men and women when attempting to prevent, control, and treat COPD, rehabilitate these patients, and improve their quality of life. | 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. | 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. | 1 |
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. | Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators.,This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair.,The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's).,In the present study we characterized the expression of Toll-like receptor (TLR)- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers.,The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age.,The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis.,In situ hybridization was performed on bronchoalveolar lavage (BAL) cells by application of the new developed HOPE-fixative.,The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes.,Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers.,In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients.,Our data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract. | 1 |
Complications of pneumonia development in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroid (ICS) therapy have been documented.,The aim of this study was to focus on clinical efficacy and the incidence of pneumonia between COPD patients receiving medium and high doses of ICS.,This prospective, randomized study included COPD patients identified from three tertiary medical centers from 2010 to 2012.,The patients were randomized into two groups: high dose (HD; fluticasone 1,000 μg + salmeterol 100 μg/day) and medium dose (MD; fluticasone 500 μg + salmeterol 100 μg/day).,Lung function with forced expiratory volume in 1 second (FEV1), forced vital capacity, and COPD-assessment test (CAT) were checked every 2 months.,The frequency of acute exacerbations and number of pneumonia events were measured.,The duration of the study period was 1 year.,In total, 237 COPD patients were randomized into the two treatment arms (115 in the HD group, 122 in the MD group).,The FEV1 level was significantly improved in the patients in the HD group compared with those in the MD group (HD 103.9±26.6 mL versus MD 51.4±19.7 mL, P<0.01) at the end of the study.,CAT scores were markedly improved in patients using an HD compared to those using an MD (HD 13±5 versus MD 16±7, P=0.05).,There was a significant difference in the percentage of annual rates in acute exacerbations (HD 0.16 versus MD 0.34, P<0.01) between the two groups.,The incidence of pneumonia was similar in the two groups (HD 0.08 versus MD 0.10, P=0.38).,COPD patients treated with high doses of ICS had more treatment benefits and no significant increases in the incidence in pneumonia.,Higher-dose ICS treatment may be suitable for COPD therapy. | The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches.,We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments.,This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk-benefit ratio of treatment.,The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone.,We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation.,COPD is a complex and challenging disease.,The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs.,An individualised programme of management can be designed and coordinated by using a case manager.,This new approach may provide tangible benefits to people with COPD. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components.,Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown.,The aim of this study was to assess the cost-utility and budget impact of tiotropium-olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.,A cost-utility study was performed, using an individual-level Markov model.,To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second) were obtained from the tiotropium-olodaterol TOnado trial.,In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium-olodaterol FDC was compared with tiotropium.,Cost-utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis.,The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%).,Both univariate and probabilistic sensitivity analyses were performed.,Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.,As a result of cost increases, combined with quality-adjusted life-year (QALY) gains, results showed that tiotropium-olodaterol FDC had an incremental cost-effectiveness ratio of €7,004/QALY.,Without discounting, the incremental cost-effectiveness ratio was €5,981/QALY.,Results were robust in univariate and probabilistic sensitivity analyses.,Budget impact was estimated at €4.3 million over 5 years assuming 100% medication adherence.,Scenarios with 40%, 60%, and 80% adherence resulted in lower 5-year incremental cost increases of €1.7, €2.6, and €3.4 million, respectively.,Tiotropium-olodaterol FDC can be considered a cost-effective treatment under current Dutch cost-effectiveness thresholds. | 1 |
The relationship between chronic obstructive pulmonary disease (COPD) and diabetes remains incompletely understood.,This study evaluated diabetes risk and post-diabetes outcomes in COPD patients with and without exacerbations.,We identified 4671 adults newly diagnosed with COPD exacerbations and 9342 adults newly diagnosed with COPD without exacerbations during 2000-2008 using Taiwan’s National Health Insurance Research Database.,A comparison cohort of 18684 adults without COPD, matched by age and sex, was randomly selected from the same dataset for the control group.,Diabetes events during 2000-2013 were ascertained from medical claims during the follow-up period.,Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with COPD with or without exacerbations were calculated.,We conducted another nested cohort study of 395516 patients with diabetes hospitalization during 2002-2013 and calculated adjusted odds ratios (ORs) and 95% CIs of histories of COPD and COPD exacerbations associated with adverse events after diabetes admission.,During the follow-up period, the incidences of diabetes for patients without COPD and for patients with COPD without or with exacerbations were 3.4, 4.1 and 7.4 per 1000 person-years, respectively (P < 0.0001).,Increased risk of diabetes for patients with COPD without exacerbations (HR 1.09, 95% CI 1.02-1.17) and COPD with exacerbations (HR 2.18, 95% CI 1.88-2.52) was noted.,Post-diabetes pneumonia (OR 3.28, 95% CI 3.13-3.43), intensive care admission (OR 1.32, 95% CI 1.26-1.39) and mortality (OR 2.06, 95% CI 1.88-2.25) were associated with COPD exacerbations.,Prevention and intervention strategies for diabetes and post-diabetes outcomes are needed for this susceptible population. | Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide.,There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder.,However, additional research is required to improve our knowledge of these relationships and their possible implications.,In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD.,We conducted a cohort study in patients from the Taiwan Longitudinal Health Insurance Database between 2000 and 2013.,Patients with COPD were identified and assessed for pre-existing and incident DM.,A Cox proportional hazards model was built to identify factors associated with incident DM and to explore the prognostic effects of DM on COPD patients.,A propensity score method was used to match COPD patients with incident DM to controls without incident DM.,Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010-1.532] for mortality than that of the COPD patients without pre-existing DM.,During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363-2.403), cerebrovascular disease (HR, 1.517; 95% CI, 1.146-2.008) and coronary artery disease (HR, 1.408; 95% CI 1.089-1.820) were significant factors associated with incident DM.,Survival was worse for the COPD patients with incident DM than for the matched controls without incident DM (Log-rank, p = 0.027).,DM, either pre-existing or incident, was associated with worse outcomes in COPD patients.,Targeted surveillance and management of DM may be important in clinical care of the COPD population. | 1 |
Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD).,Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking.,The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-α), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD.,This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center.,Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry.,Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%).,On bivariate analysis, there was no association between TNF-α and BMD.,Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density.,However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability.,Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis.,The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis.,We conclude that the effect of adipokines on BMD does not appear to be independent of body mass.,However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally.,Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD.,Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality.,Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes.,In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels.,To date, only limited evidence exists to support the effectiveness of these interventions.,We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. | 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. | 1 |
Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD).,Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.,We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.,Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined.,Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD.,Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.,Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression.,Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR.,ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased.,Healthy smokers were intermediate between healthy nonsmokers and patients with COPD.,Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects.,MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.,Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation.,Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. | Asthma and chronic obstructive pulmonary disease (COPD) are characterized by different patterns of airway remodeling, which all include an increased mass of bronchial smooth muscle (BSM).,A remaining major question concerns the mechanisms underlying such a remodeling of BSM.,Because mitochondria play a major role in both cell proliferation and apoptosis, we hypothesized that mitochondrial activation in BSM could play a role in this remodeling.,We describe that both the mitochondrial mass and oxygen consumption were higher in the BSM from asthmatic subjects than in that from both COPD and controls.,This feature, which is specific to asthma, was related to an enhanced mitochondrial biogenesis through up-regulation of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A.,The priming event of such activation was an alteration in BSM calcium homeostasis.,BSM cell apoptosis was not different in the three groups of subjects.,Asthmatic BSM was, however, characterized by increased cell growth and proliferation.,Both characteristics were completely abrogated in mitochondria-deficient asthmatic BSM cells.,Conversely, in both COPD and control BSM cells, induction of mitochondrial biogenesis reproduced these characteristics.,Thus, BSM in asthmatic patients is characterized by an altered calcium homeostasis that increases mitochondrial biogenesis, which, in turn, enhances cell proliferation, leading to airway remodeling. | 1 |
The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD).,Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents.,This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.,5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat® inhaler).,Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline).,Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.,Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05).,FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.,Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment.,Improvements from baseline in lung function were generally greater in patients with less severe disease.,Boehringer Ingelheim.,Trial registration: ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.,The online version of this article (doi:10.1007/s12325-015-0218-0) contains supplementary material, which is available to authorized users. | Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD).,This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone.,Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI).,Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values.,This suggests that the effect of combining a LABA and a LAMA is not fully additive.,LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents.,Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes.,LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations.,The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. | 1 |
Previously we generated a chronic obstructive pulmonary disease (COPD) specific knowledge base (http://www.copdknowledgebase.eu) from clinical and experimental data, text-mining results and public databases.,This knowledge base allowed the retrieval of specific molecular networks together with integrated clinical and experimental data.,The COPDKB has now been extended to integrate over 40 public data sources on functional interaction (e.g. signal transduction, transcriptional regulation, protein-protein interaction, gene-disease association).,In addition we integrated COPD-specific expression and co-morbidity networks connecting over 6 000 genes/proteins with physiological parameters and disease states.,Three mathematical models describing different aspects of systemic effects of COPD were connected to clinical and experimental data.,We have completely redesigned the technical architecture of the user interface and now provide html and web browser-based access and form-based searches.,A network search enables the use of interconnecting information and the generation of disease-specific sub-networks from general knowledge.,Integration with the Synergy-COPD Simulation Environment enables multi-scale integrated simulation of individual computational models while integration with a Clinical Decision Support System allows delivery into clinical practice.,The COPD Knowledge Base is the only publicly available knowledge resource dedicated to COPD and combining genetic information with molecular, physiological and clinical data as well as mathematical modelling.,Its integrated analysis functions provide overviews about clinical trends and connections while its semantically mapped content enables complex analysis approaches.,We plan to further extend the COPDKB by offering it as a repository to publish and semantically integrate data from relevant clinical trials.,The COPDKB is freely available after registration at http://www.copdknowledgebase.eu. | Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation.,Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy.,Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate.,In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators.,Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles.,Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization.,These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. | 1 |
Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. | Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD).,This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.,Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days.,Treatment was repeated every 8 weeks for a total of six courses.,Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.,At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).,There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores.,There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006).,Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility.,There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).,Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline.,There were no unexpected adverse events and there was no evidence of resistance development.,ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov). | 1 |
COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 176 consecutive hospitalized patients with AECOPD were included.,The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected.,The re-exacerbation rate in 90 days was 48.9% (86 out of 176).,It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test.,A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay).,The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001).,A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD.,Further studies are required to verify these findings. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV1).,This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated.,We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients.,This was a record-linkage study using patients registered with a Scottish regional COPD network 2000-2015.,Annual spirometry & symptoms were recorded and linked to healthcare records to identify exacerbations, hospitalisations and mortality.,Spirometry, modified Medical Research Council (mMRC) dyspnoea scale and acute exacerbations over the previous year were used to assign GOLD severity at each visit.,A time-dependent Cox model was used to model time to death.,Secondary outcomes were respiratory specific mortality and hospitalisations.,Effect sizes are expressed as Hazard Ratios HR (95%CI).,Four thousand, eight hundred and eighty-five patients (mean age 67.3 years; 51.3% female) with 21,348 visits were included.,During a median 6.6 years follow-up there were 1530 deaths.,For the secondary outcomes there were 712 respiratory deaths and 1629 first hospitalisations.,Across 16,463 visit-pairs, improvement in COPD severity was seen in 2308 (14%), no change in 11,010 (66.9%) and worsening in 3145 (19.1).,Compared to patients staying in GOLD stage A, those worsening had a stepwise increased mortality and hospitalisations.,Improving COPD severity classification was associated with reduced mortality and worsening COPD severity was associated with increased mortality and hospitalisations.,Change in GOLD group has potential as monitoring tool and outcome measure in clinical trials.,The online version of this article (10.1186/s12931-018-0960-3) contains supplementary material, which is available to authorized users. | 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. | 1 |
Tiotropium is an anticholinergic bronchodilator for symptom relief and reducing exacerbations with an established safety profile in patients with chronic obstructive pulmonary disease (COPD).,Using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study, we re-evaluated the safety of tiotropium HandiHaler® in patients who experienced recent myocardial infarction (MI), heart failure or unstable rhythm disorder during the study.,A post-hoc analysis of all-cause mortality and serious cardiac adverse events (cardiac SAEs), including cardiac deaths and death unknown, was conducted in patients who had experienced cardiac arrhythmia, MI or cardiac failure during UPLIFT® and who completed the study.,Descriptive analyses were performed.,Most patients experiencing cardiac events, for which they would have been excluded at baseline, remained in the trial.,Kaplan-Meier analyses revealed a trend to later occurrence of cardiac SAEs with tiotropium HandiHaler® versus placebo.,Patients who experienced a cardiac event and continued in UPLIFT® were not found to be at subsequently increased risk of all-cause mortality or cardiac SAEs with tiotropium treatment.,Evaluation of deaths by major adverse cardiac events composite endpoints also showed that patients treated with tiotropium were not at increased risk of mortality or cardiac SAEs compared with placebo.,Risk of cardiac events, mortality or SAEs was not increased by tiotropium in patients experiencing cardiac events for which they would have been excluded at study baseline.,The findings support the cardiac safety of tiotropium HandiHaler® in patients with COPD.,The online version of this article (doi:10.1186/s12931-015-0216-4) contains supplementary material, which is available to authorized users. | Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | 1 |
The morbidity and mortality associated with COPD exacts a considerable economic burden.,Comorbidities in COPD are associated with poor health outcomes and increased costs.,Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.,This was a retrospective observational study of data from the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplemental Databases from January 1, 2009, to September 30, 2012.,Resource consumption was measured from the index date (date of first occurrence of non-rule-out COPD diagnosis) to 360 days after the index date.,Resource use (all-cause and disease-specific [ie, COPD- or asthma-related] ED visits, hospitalizations, office visits, other outpatient visits, and total length of hospital stay) and health-care costs (all-cause and disease-specific costs for ED visits, hospitalizations, office visits, and other outpatient visits and medical, prescription, and total health-care costs) were assessed.,Generalized linear models were used to evaluate the impact of comorbidities on total health-care costs, adjusting for age, sex, geographic location, baseline health-care use, employment status, and index COPD medication.,Among 183,681 patients with COPD, the most common comorbidities were cardiovascular disease (34.8%), diabetes (22.8%), asthma (14.7%), and anemia (14.2%).,Most patients (52.8%) had one or two comorbidities of interest.,The average all-cause total health-care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ($41,288) and anemia ($38,870).,The impact on total health-care costs was greatest for anemia ($10,762 more, on average, than a patient with COPD without anemia).,Our analysis demonstrated that high resource use and costs were associated with COPD and multiple comorbidities. | 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 |
Chronic respiratory diseases are a significant cause of morbidity and mortality worldwide.,We sought to evaluate the impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities in adults.,In the Gene Environment Interactions in Respiratory Diseases study (2007/2010), a screening questionnaire was mailed to 9,739 subjects aged 20-44 (response rate: 53.0%) and to 3,480 subjects aged 45-64 (response rate: 62.3%), who were randomly selected from the general population in Italy.,The questionnaire was used to: identify the responders who had asthma, chronic bronchitis, allergic rhinitis or asthma-like symptoms/dyspnoea/other nasal problems; evaluate the total burden [use of hospital services (at least one ED visit and/or one hospital admission) and number of days with reduced activities (lost working days and days with limited, not work related activities) due to any health problems (apart from accidents and injuries) in the past three months]; evaluate the contribution of breathing problems to the total burden (hospitalizations and number of days with reduced activities specifically due to breathing problems).,At any age, the all-cause hospitalization risk was about 6% among the subjects without any respiratory conditions, it increased to about 9-12% among the individuals with allergic rhinitis or with asthma-like symptoms/dyspnoea/other nasal problems, and it peaked at about 15-18% among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively.,The expected number of days with reduced activities due to any health problems increased from 1.5 among the subjects with no respiratory conditions in both the age classes, to 6.3 and 4.6 among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively.,The contribution of breathing problems to the total burden was the highest among the asthmatics with chronic bronchitis (23-29% of the hospitalization risk and 39-50% of the days with reduced activities, according to age).,The impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities is substantial, and it is markedly different among adults from the general population in Italy.,The contribution of breathing problems to the total burden also varies according to the respiratory condition. | Chronic obstructive pulmonary disease (COPD) can affect cognition.,The effects of other less severe chronic airway disorders on cognition remain to be clarified.,This study aimed to measure and compare cognitive deterioration in subjects with COPD, subjects with chronic non-obstructive bronchitis (CNOB), and asymptomatic smokers (AS), and to relate the corresponding prevalence to several demographic and clinical variables and to normal reference values.,Four hundred and two subjects (COPD n=229, CNOB n=127, and AS n=46) of comparable age were included in the study.,Cognitive impairment was assessed using the Mini Mental Status test, the Clock Drawing test, and the Trail Making test A and B.,The extent and prevalence of cognitive deterioration was greater in COPD subjects, followed by CNOB subjects and AS (P<0.001).,The Medical Research Council and COPD Assessment test scores, forced expiratory volume in the first second predicted, and arterial partial pressure of O2 and of CO2 were related to the extent and the prevalence of cognitive deterioration.,COPD subjects, CNOB subjects, and AS aged 40-69 years showed the greatest cognitive impairment (P<0.01 compared to normal values).,This was particularly clear in COPD subjects.,Cognitive impairment may start at the early stages of chronic airway damage and progress with a worsening of the respiratory condition.,Indeed, the greatest cognitive deterioration was seen in COPD subjects.,Cognition impairment may contribute to explaining the insufficient adherence to therapeutic plans and strategies, and the increasing social costs in respiratory subjects. | 1 |
The prevalence rate of bronchiectasis in COPD is variable.,Coexisting bronchiectasis and COPD may influence COPD severity and exacerbation.,We investigated whether bronchiectasis is associated with frequent or severe COPD exacerbation.,Lower airway bacterial and mycobacterial infections are a possible mechanism for bronchiectasis.,A cross-sectional study was conducted in 2013-2014.,COPD exacerbations and hospitalizations were reviewed.,Spirometry and CT were performed.,COPD symptoms were assessed by using the COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale.,Sputum inductions were performed and specimens were sent for microbiology.,We recruited 72 patients.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, B, C, and D, were noted in 20%, 27.1%, 14.3%, and 38.6% of the patients, respectively.,Frequent exacerbations (≥2) and/or ≥1 hospitalization in the previous year were observed in 40.3% of patients.,Median mMRC of COPD with frequent and non-frequent exacerbations was 1.0 (range 1-2) and 2.0 (range 1-3), (p=0.002), respectively.,Median CAT of COPD with frequent and non-frequent exacerbations was 20.5 (3-37) and 11.0 (2-32), (p=0.004), respectively.,CT-detected bronchiectasis was observed in 47.2% of patients.,Median mMRC of COPD with and without bronchiectasis was 1.0 (0-4) and 1.0 (0-4) (p=0.22), respectively.,Median CAT of COPD with and without bronchiectasis was 16.2 (95% CI: 12.9-19.6) and 13.0 (3-37), (p=0.49), respectively.,The lower post-bronchodilator forced expiratory volume in 1 second (FEV1) of COPD with frequent exacerbations than those without was noted (p=0.007).,The post-bronchodilator forced expiratory volume at 1 second percent in patients with and without bronchiectasis was not different (p=0.91).,After adjusting for gender, severity of airflow obstruction, severity of COPD symptoms, the odds ratio for bronchiectasis with frequent and/or severe exacerbation was 4.99 (95% CI: 1.31-18.94), (p=0.018).,Neither bacterial nor mycobacterial airway infection was associated with bronchiectasis or frequent exacerbation.,Bronchiectasis is common in Thai COPD.,It was associated with frequent exacerbation or hospitalization.,Mycobacterial tuberculosis in COPD patients with bronchiectasis was uncommon. | Bronchiectasis is prevalent in patients with COPD.,The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China.,Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed.,SPSS statistical software was used to analyze the data.,Data from 896 patients with COPD were analyzed.,Bronchiectasis was present in 311 patients.,The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35-6.37; P = 0.007).,During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group.,The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02-3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD.,These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum.,Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD. | 1 |
The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | Patients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease.,We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS).,Identification of the items forming the CASIS was guided by patient interviews and focus groups.,An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure.,Qualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma).,The observational study included 311 patients with COPD and 324 patients with asthma.,The final seven items used in the CASIS were identified based on factor and item response theory analyses.,Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups).,In the COPD sample, CASIS scores were significantly correlated with the Saint George's Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.005).,In the asthma sample, CASIS scores were significantly correlated with the Asthma Quality of Life Questionnaire scores (all p < 0.0001) and differed significantly by clinician and patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.0005).,The CASIS shows good internal consistency, test-retest reliability, and construct validity and may be useful in helping to understand the impact that COPD and asthma have on sleep outcomes. | 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. | One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days.,No tool has been developed specifically in this population to predict readmission or death.,Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement.,In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records.,A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort).,Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores.,Of 2417 patients, 936 were readmitted or died within 90 days of discharge.,The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL).,The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts.,Higher PEARL scores were associated with a shorter time to readmission.,The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting.,It is superior to other scores that have been used in this population.,UKCRN ID 14214. | 1 |
Altered cardiac repolarization and increased dispersion of repolarization have been identified as risk factors for sudden cardiac death (SCD).,The prevalence of and the mechanisms contributing to altered cardiac repolarization are currently unknown in COPD.,In 91 COPD patients, 32 controls matched for age, cardiovascular risk and medication, and 41 healthy subjects, measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) were derived from 12-lead electrocardiography (ECG).,Prevalence rates of heart rate corrected QT (QTc) >450ms and QT dispersion >60ms were determined to assess the number of subjects at risk for SCD.,Univariate and multivariate analyses were used to identify possible factors contributing to altered cardiac repolarization.,QTc was found to be prolonged in 31.9% and QT dispersion in 24.2% of the COPD patients compared to 12.5% in matched controls and 0% in healthy subjects.,The QTc interval was longer in COPD patients compared to matched and healthy controls respectively (437.9 ± 29.5 vs.,420.1 ± 25.3 ms, p = 0.001 and vs.,413.4 ± 18.2 ms, p < 0.001).,QT dispersion was significantly increased in COPD patients compared to healthy subjects (45.4 (34.8 , 59.5) vs.,39.7 (29.3 , 54.8) ms, p = 0.049).,Only oxygen saturation was independently associated with QTc duration in multivariate analysis (β = -0.29, p = 0.015).,One third of a typical COPD population has altered cardiac repolarization and increased dispersion of repolarization, which may be related to hypoxia.,Altered cardiac repolarization may expose these patients to an increased risk for malignant ventricular arrhythmias and SCD. | Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants.,COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function.,The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature.,Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. | 1 |
Studies report high in-hospital mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) especially for those requiring admission to an intensive care unit.,Recognizing factors associated with mortality in these patients could reduce health care costs and improve end-of-life care.,This retrospective study included AECOPD patients admitted to the respiratory intensive care unit of a tertiary hospital in Beijing from Jan 1, 2011 to Dec 31, 2018.,Patients demographic characteristics, blood test results and comorbidities were extracted from the electronic medical record system and compared between survivors and non-survivors.,We finally enrolled 384 AECOPD patients: 44 (11.5%) patients died in hospital and 340 (88.5%) were discharged.,The most common comorbidity was respiratory failure (294 (76.6%)), followed by hypertension (214 (55.7%)), coronary heart disease (115 (29.9%)) and chronic heart failure (76 (19.8%)).,Multiple logistic regression analysis revealed that independent risk factors associated with in-hospital mortality included lymphocytopenia, leukopenia, chronic heart failure and requirement for invasive mechanical ventilation.,The in-hospital mortality of patients with acute COPD exacerbation requiring RICU admission is high.,Lymphocytes < 0.8 × 109/L, leukopenia, requirement for invasive mechanical ventilation, and chronic heart failure were identified as risk factors associated with increased mortality rates. | Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker.,However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD).,This study was aimed to evaluate the usefulness of NLR in patients with COPD.,NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28).,NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period.,The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression.,NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001).,NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs.,11.5 ± 8.8, p < 0.001).,NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale.,NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079).,Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization.,NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD. | 1 |
COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema.,Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking.,Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis.,Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered.,However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis.,It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed “selective autophagy” and that this process is related to the pathogenesis of human diseases.,In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD.,Strategies targeting these pathways may yield novel therapies for COPD. | The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention.,Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance.,Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways.,Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins.,In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy.,During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction.,Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase. | 1 |
To develop and do an initial validation of a new simple tool (self-administered questionnaire) that would be sensitive and specific enough to detect early changes in smokers leading to future development of chronic obstructive pulmonary disease (COPD).,224 consecutive participants (50.9% women), with mean ± standard deviation age of 52.3 ± 6.7 years, 37.5 ± 16.7 pack-years smoking history (85.8% active smokers), and no prior diagnosis of COPD were recruited.,The MARKO questionnaire was self-administered twice; at the general practitioner's office and after 2-4 weeks at the tertiary care hospital.,Participants were assessed for COPD by a pulmonologist after filling in a quality of life (QoL) questionnaires, history-taking, physical examination, lung function test, 6-minute walk test, and laboratory tests.,They were divided into four subgroups: “healthy” smokers, symptomatic smokers, and smokers with mild and moderately severe COPD.,Psychometric analyses indicated that the 18-item questionnaire had a very good internal consistency (Cronbach’s alpha = 0.91) and test-retest reliability for a four week period (ρc = 0.89, 95% confidence interval [CI] 0.85-0.92, Lin’s concordance).,A significant correlations of MARKO scores were found with two QoL questionnaires; r = 0.69 (P < 0.001) and r = 0.81 (P < 0.001).,Receiver operating characteristic curve analysis showed an area under the curve of 0.753 (95% CI 0.691-0.808, P < 0.001), with a sensitivity of 71.83% and specificity of 64.24% to discriminate “healthy” smokers from other subgroups.,Based on psychometric analyses and high convergent validity correlation with already validated QoL questionnaires, the newly developed MARKO questionnaire was shown to be a reliable self-administered short health status assessment tool.,Clinicaltrial.gov NCT01550679 | Influencing the progression of COPD has long been an elusive goal of drug therapy.,Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®).,Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced.,The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD.,The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease.,With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. | 1 |
Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | 1 |
In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | COPD is associated with different comorbid diseases, and their frequency increases with age.,Comorbidities severely impact costs of health care, intensity of symptoms, quality of life and, most importantly, may contribute to life span shortening.,Some comorbidities are well acknowledged and established in doctors’ awareness.,However, both everyday practice and literature searches provide evidence of other, less recognized diseases, which are frequently associated with COPD.,We call them underrecognized comorbidities, and the reason why this is so may be related to their relatively low clinical significance, inefficient literature data, or data ambiguity.,In this review, we describe rhinosinusitis, skin abnormalities, eye diseases, different endocrinological disorders, and gastroesophageal reflux disease.,Possible links to COPD pathogenesis have been discussed, if the data were available. | 1 |
Directly recorded patient experience of symptoms and health-related quality of life (HRQoL) can complement lung function and exacerbation rate data in chronic obstructive pulmonary disease (COPD) clinical studies.,The FULFIL study recorded daily symptoms and activity limitation together with additional patient-reported outcomes of dyspnea and HRQoL, as part of the prespecified analyses.,FULFIL co-primary endpoint data have been previously reported.,FULFIL was a phase III, 24-week, randomized, double-blind, double-dummy, multicenter study comparing once-daily single inhaler triple therapy [fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)] 100 µg/62.5 µg/25 µg with twice-daily inhaled corticosteroid/long-acting β2-agonist therapy [budesonide/formoterol (BUD/FOR)] 400 µg/12 µg in patients with symptomatic COPD at risk of exacerbations.,A subset participated for 52 weeks.,Patient-reported assessments were: Evaluating Respiratory Symptoms in COPD™ (E-RS: COPD), St George’s Respiratory Questionnaire (SGRQ) for COPD, COPD Assessment Test (CAT), baseline and transitional dyspnea indices (TDI) and daily and global anchor questions for activity limitation.,FF/UMEC/VI showed greater reductions from baseline in 4-weekly mean E-RS: COPD total and all subscale scores compared with BUD/FOR; differences were statistically significant (P < 0.05) at each time period.,FF/UMEC/VI also demonstrated greater improvements from baseline at weeks 4 and 24 in SGRQ domain scores and TDI focal score compared with BUD/FOR.,At weeks 4 and 24, improvements greater than the minimal clinically important difference from baseline were observed in CAT score with FF/UMEC/VI, but not BUD/FOR; differences were statistically significant (P ≤ 0.003).,These findings demonstrate sustained daily symptom and HRQoL benefits of FF/UMEC/VI versus BUD/FOR.,The inclusion of the CAT may provide data that are readily generalizable to everyday clinical practice.,ClinicalTrials.gov number: NCT02345161.,GSK.,The online version of this article (10.1007/s12325-017-0650-4) contains supplementary material, which is available to authorized users. | Many patients with chronic obstructive pulmonary disease (COPD) receive inhaled corticosteroids (ICSs) without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest.,DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany.,A subgroup of patients were taking ICS prior to entry - 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients.,Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal.,Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma.,Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded.,There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients.,During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group.,COPD Assessment Test total score improved from baseline in both groups.,These data suggest that ICS withdrawal is possible with no increased risk of exacerbations in patients with COPD managed in the primary and secondary care. | 1 |
The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | 1 |
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies. | Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | 1 |
Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations.,Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown.,We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection.,Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus.,Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages.,In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured.,Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD.,O&NS markers correlated with virus load and inflammatory markers.,Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress.,Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation.,Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines.,O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations.,Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations. | Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory airway disease often associated with cigarette smoke (CS) exposure.,The disease is increasing in global prevalence and there is no effective therapy.,A major step forward would be to understand the disease pathogenesis.,The ATP-P2X7 pathway plays a dominant role in murine models of CS induced airway inflammation, and markers of activation of this axis are upregulated in patients with COPD.,This strongly suggests that the axis could be important in the pathogenesis of COPD.,The aim of this study was to perform a detailed characterisation of the signalling pathway components involved in the CS-driven, P2X7 dependent airway inflammation.,We used a murine model system, bioassays and a range of genetically modified mice to better understand this complex signalling pathway.,The inflammasome-associated proteins NALP3 and ASC, but not IPAF and AIM2, are required for CS-induced IL-1β/IL-18 release, but not IL-1α.,This was associated with a partial decrease in lung tissue caspase 1 activity and BALF neutrophilia.,Mice missing caspase 1/11 or caspase 11 had markedly attenuated levels of all three cytokines and neutrophilia.,Finally the mechanism by which these inflammatory proteins are involved in the CS-induced neutrophilia appeared to be via the induction of proteins involved in neutrophil transmigration e.g.,E-Selectin.,This data indicates a key role for the P2X7-NALP3/ASC-caspase1/11-IL-1β/IL-18 axis in CS induced airway inflammation, highlighting this pathway as a possible therapeutic target for the treatment of COPD. | 1 |
Spirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema.,We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow-volume loops.,We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts.,A computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence.,The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them.,The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema.,Findings were validated in an independent group of 340 individuals.,AC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001).,Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001).,Similar associations were obtained when using CT-automated density scores for emphysema assessment.,Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity).,Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects.,When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated.,Airway collapse on forced expiration quantified by a computer model correlates with emphysema.,An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers. | Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques. | 1 |
Comprehensive multidisciplinary pulmonary rehabilitation is vital in the management of chronic obstructive pulmonary disease (COPD) and is considered for any stage of the disease.,Rehabilitation programmes are often centre-based and organised in groups.,However, the distance from the patient’s home to the centre and lack of transportation may hinder participation.,Rehabilitation at home can improve access to care for patients regardless of disease severity.,We had previously studied the technology usability and acceptability of a comprehensive home rehabilitation programme designed for patients with very severe COPD receiving long-term oxygen therapy.,The acceptability of such comprehensive home programmes for those with less severe COPD, who may be less homebound, is not known.,The aims of this feasibility study were to assess patient acceptability of the delivery mode and components of a comprehensive pulmonary rehabilitation programme for any stage of COPD, as well as the technology usability, patient outcomes and economic aspects.,Ten participants with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade I-IV were enrolled in a 9-week home programme and divided into two rehabilitation groups, with five patients in each group.,The programme included exercise training and self-management education in online groups of patients, and individual online consultations.,The patients also kept a digital health diary.,To assess the acceptability of the programme, the patients were interviewed after the intervention using a semi-structured interview guide.,In addition the number of sessions attended was observed.,The usability of the technology was assessed using interviews and the System Usability Scale questionnaire.,The St George’s Respiratory Questionnaire (SGRQ) was used to measure health-related quality of life.,The mode of delivery and the components of the programme were well accepted by the patients.,The programme provided an environment for learning from both healthcare professionals and peers, for asking questions and discussing disease-related issues and for group exercising.,The patients considered that it facilitated health-enhancing behaviours and social interactions with a social group formed among the participants.,Even participants who were potentially less homebound appreciated the home group and social aspects of the programme.,The participants found the technology easy to learn and use.,The acceptability and usability results were consistent with those in our previous study of patients with very severe COPD.,Only the mean change in the SGRQ total score of −6.53 (CI 95 % −0.38 to −12.68, p = 0.04) indicates a probable clinically significant effect.,Economic calculations indicated that the cost of the programme was feasible.,The results of this study indicate that comprehensive pulmonary rehabilitation delivered in home-based online groups may be feasible in COPD.,The mode of delivery and components of the programme appeared to be acceptable across patients with different disease severity.,The results in terms of patient outcomes are inconclusive, and further assessment is needed. | Patient-reported outcomes (PRO) questionnaires are being increasingly used in COPD clinical studies.,The challenge facing investigators is to determine what change is significant, ie what is the minimal clinically important difference (MCID).,This study aimed to identify the MCID for the clinical COPD questionnaire (CCQ) in terms of patient referencing, criterion referencing, and by the standard error of measurement (SEM).,Patients were ≥40 years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and were participating in a randomized, controlled clinical trial comparing intravenous and oral prednisolone in patients admitted with an acute exacerbation of COPD.,The CCQ was completed on Days 1-7 and 42.,A Global Rating of Change (GRC) assessment was taken to establish the MCID by patient referencing.,For criterion referencing, health events during a period of 1 year after Day 42 were included in this analysis.,210 patients were recruited, 168 completed the CCQ questionnaire on Day42.,The MCID of the CCQ total score, as indicated by patient referencing in terms of the GRC, was 0.44.,The MCID of the CCQ in terms of criterion referencing for the major outcomes was 0.39, and calculation of the SEM resulted in a value of 0.21.,This investigation, which is the first to determine the MCID of a PRO questionnaire via more than one approach, indicates that the MCID of the CCQ total score is 0.4. | 1 |
COPD self-management reduces hospital admissions and improves health-related quality of life (HRQoL).,However, whilst most patients are managed in primary care, the majority of self-management trials have recruited participants with more severe disease from secondary care.,We report the findings of a systematic review of the effectiveness of community-based self-management interventions in primary care patients with COPD.,We systematically searched eleven electronic databases and identified 12 eligible randomised controlled trials with seven included in meta-analyses for HRQoL, anxiety and depression.,We report no difference in HRQoL at final follow-up (St George’s Respiratory Questionnaire total score −0.29; 95%CI −2.09, 1.51; I2 0%), nor any difference in anxiety or depression.,In conclusion, supported self-management interventions delivered in the community to patients from primary care do not appear to be effective.,Further research is recommended to identify effective self-management interventions suitable for primary care populations, particularly those with milder disease.,Further work is needed to ensure that self-management of chronic lung disease in primary care settings actively improves patients’ quality of life.,While self-management is beneficial to patients in secondary care with severe chronic obstructive pulmonary disease (COPD), few studies have examined self-management effectiveness in primary care patients with milder COPD.,Kate Jolly at the University of Birmingham, UK, and co-workers identified only 12 studies out of over 12,500 that specifically examined self-management in primary care.,Of these, seven were suitable for metanalysis.,The team found that community-based interventions to support self-management did not make a significant difference to patients’ perceived quality of life, or in reducing anxiety and depression.,They call for further research to identify specific support that will help patients with mild to moderate COPD cope and adapt to the progressive condition. | This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China.,This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD.,Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly.,Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD.,Control group patients received usual care.,The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD.,COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05).,A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients.,The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05).,The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05).,A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD. | 1 |
This study aimed to investigate the serum inflammatory cytokines levels in patients with COPD, pneumonia and lung cancer, and assess the correlation between the levels of inflammatory cytokines levels and development of these diseases.,Two hundred thirty-two patients including 114 patients with pneumonia, 76 patients with chronic obstructive pulmonary disease (COPD) and 42 patients with lung cancer, and 62 age-matched healthy volunteers as controls were enrolled.,The pro-inflammatory cytokine IL-6, IL-2, IFN-γ, TNF-α, anti-inflammatory cytokines IL-4 and IL-10 in serum were analyzed by flow cytometry microsphere array (CBA).,We found that the levels of TNF-α and IL-10 in patients with lung cancer, COPD and pneumonia were significantly higher than control group.,The IL-6 in the lung cancer group were significantly increased compared with the controls and COPD group, pneumonia group.,IFN-γ and IL-2 levels were lower in lung cancer compared with controls and COPD group, pneumonia group.,TNF-α, IL-4 and IL-10 levels were increased in patients with COPD and pneumonia compared with controls.,In addition, the concentrations of IFN-γ and IL-6 were increased in acute exacerbation COPD (AECOPD) group compared with stable COPD group.,In conclusion, elevated TNF-α and IL-10 levels in serum may be related with lung diseases including lung cancer, COPD and pneumonia.,Additionally, IFN-γ and IL-6 might be potential biomarkers for the further deterioration of lung disease patients.,The increased concentrations of IFN-γ and IL-6 might be used to predict the exacerbation of COPD. | Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung.,Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways.,Bacterial variety diminishes with increasing COPD severity.,Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections.,In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD.,In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial-viral infections and related immune response in COPD phenotypes need to be better clarified.,Our paper would address these points that we consider of great importance for the clinical management of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a severe public health threat world-wide.,Cigarette smoke (CS)-induced airway epithelial cell death is a major pathway of pathogenesis in emphysema, a subtype of COPD.,Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that catalyzes mono- and di-methylation on arginine residues within histone and non-histone proteins to modulate a variety of life processes, such as apoptosis.,However, its role in CS-induced lung epithelial death has not been fully elucidated.,Here we report that PRMT6 was decreased in mouse lung tissues from a cigarette smoke extract (CSE)-mediated experimental emphysematous model and in CSE treated or cigarette smoke exposed lung epithelial cells.,Depletion of PRMT6 increased the protein levels of phosphatase PTEN and PI3K regulatory subunit p85 but decreased a downstream kinase PDK1, resulting in AKT dephosphorylation and thereafter, lung epithelial cell death.,Knockout of PRMT6 inhibited epithelial survival and promoted CSE-mediated epithelial cell death, while ectopic expression of PRMT6 protein partially reversed epithelial cell death via PI3K/AKT-mediated cell survival signaling in CSE cellular models.,These findings demonstrate that PRMT6 plays a crucial role in CS-induced bronchial epithelial cell death that may be a potential therapeutic target against the airway cell death in CS-induced COPD. | This study aimed to explore cytokine serum levels and the ratio of type 1 T helper (Th1)/Th2 cells in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,A total 245 patients diagnosed with AECOPD and 193 patients who progressed to stable COPD after the initiation of treatment in hospital were selected, while a further 50 healthy individuals served as controls.,All patients with COPD were diagnosed using Global Initiative for Chronic Obstructive Lung Disease criteria.,Serum concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-10, IL-17, and immunoglobulin (Ig)E were measured using enzyme-linked immunosorbent assays.,AECOPD patients had higher levels of IL-2, IFN-γ, IL-4, IL-10, IL-17, and IgE than those with stable COPD or controls.,Intriguingly, the ratios of Th1/Th2 and IL-17/IgE were lower in AECOPD patients compared with the other two groups.,These data suggest that AECOPD patients produce more IgE and have more differentiated Th2 cells than other groups.,Our findings suggest that an imbalance of circulating CD4+ T cell subsets correlates with AECOPD, and that a shift of Th1/Th2 and IL-17/IgE ratios may be caused by increased Th2 cell production. | 1 |
Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined.,We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function.,NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome.,Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation.,Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001).,This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002).,Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01).,Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes.,Consistent results were observed regardless of the method of quantifying sputum NETs.,Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD.,NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity. | Smoking is a well-established risk factor for rheumatoid arthritis (RA), and it has been proposed that smoking-induced citrullination renders autoantigens immunogenic.,To investigate this mechanism, we examined human lung tissue from 40 subjects with defined smoking status, with or without chronic obstructive pulmonary disease (COPD), and control tissues from other organs for citrullinated proteins and the deiminating enzymes peptidylarginine deiminase type-2 (PAD2) and -4 (PAD4).,Lung tissue samples, dissected from lobectomy specimens from 10 never smokers, 10 smokers without airflow limitation, 13 COPD smokers and eight COPD ex-smokers, and control tissue samples (spleen, skeletal muscle, liver, ovary, lymph node, kidney and heart), were analysed for citrullinated proteins, PAD2 and PAD4 by immunoblotting.,Citrulline and homocitrulline residues in enolase and vimentin were analysed by partial purification by gel electrophoresis followed by mass spectrometry in 12 of the lung samples and one from each control tissues.,Band intensities were scored semi-quantitatively and analysed by two-tailed Mann-Whitney T-test.,Within the lung tissue samples, citrullinated proteins, PAD2 and PAD4 were found in all samples, with an increase in citrullination in COPD (P = 0.039), but minimal difference between smokers and non-smokers (P = 0.77).,Citrullination was also detected at lower levels in the tissues from other organs, principally in lymph node, kidney and skeletal muscle.,Mass spectrometry of the lung samples showed that vimentin was citrullinated at positions 71, 304, 346, 410 and 450 in non-smokers and smokers both with and without COPD.,A homocitrulline at position 104 was found in four out of six COPD samples and one out of six non-COPD.,Citrulline-450 was also found in three of the control tissues.,There were no citrulline or homocitrulline residues demonstrated in α-enolase.,We have shown evidence of citrullination of vimentin, a major autoantigen in RA, in both non-smokers and smokers.,The increase in citrullinated proteins in COPD suggests that citrullination in the lungs of smokers is mainly due to inflammation.,The ubiquity of citrullination of vimentin in the lungs and other tissues suggests that the relationship between smoking and autoimmunity in RA may be more complex than previously thought.,The online version of this article (doi:10.1186/s13075-015-0520-x) contains supplementary material, which is available to authorized users. | 1 |
Is the neutrophil to lymphocyte ratio (NLR) associated with lung function decline and chronic obstructive pulmonary disease risk at the population level?,This cohort study of 1549 US veterans with more than 30 years of follow-up found that higher NLR was associated with lower lung function and higher chronic obstructive pulmonary disease risk.,Additionally, NLR was associated with AHRR hypomethylation, the top DNA methylation signature of lung function changes, which may mediate the adverse association of NLR-related inflammation with lung function.,These findings suggest that NLR may be a useful, readily obtainable, and inexpensive tool to identify people with high risks of lung function impairment and chronic obstructive pulmonary disease.,This cohort study examines the associations of neutrophil to lymphocyte ratio with lung function and risk of chronic obstructive pulmonary disease among US veterans with up to 30 years of follow-up.,Chronic obstructive pulmonary disease (COPD) is a critical public health burden.,The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood.,To explore the associations of NLR with lung function decline and COPD risks.,This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking.,This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018.,A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD.,Data were analyzed from September 2019 to January 2020.,The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit.,The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits.,The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria.,Both outcomes were measured as each visit.,Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF.,Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function.,Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline.,Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function.,These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles. | COPD has been perceived as being a disease of older men.,However, >7 million women are estimated to live with COPD in the USA alone.,Despite a growing body of literature suggesting an increasing burden of COPD in women, the evidence is limited.,To assess and synthesize the available evidence among population-based epidemiologic studies and calculate the global prevalence of COPD in men and women.,A systematic review and meta-analysis reporting gender-specific prevalence of COPD was undertaken.,Gender-specific prevalence estimates were abstracted from relevant studies.,Associated patient characteristics as well as custom variables pertaining to the diagnostic method and other important epidemiologic covariates were also collected.,A Bayesian random-effects meta-analysis was performed investigating gender-specific prevalence of COPD stratified by age, geography, calendar time, study setting, diagnostic method, and disease severity.,Among 194 eligible studies, summary prevalence was 9.23% (95% credible interval [CrI]: 8.16%-10.36%) in men and 6.16% (95% CrI: 5.41%-6.95%) in women.,Gender prevalences varied widely by the World Health Organization Global Burden of Disease subregions, with the highest female prevalence found in North America (8.07% vs 7.30%) and in participants in urban settings (13.03% vs 8.34%).,Meta-regression indicated that age ≥40 and bronchodilator testing contributed most significantly to heterogeneity of prevalence estimates across studies.,We conducted the largest ever systematic review and meta-analysis of global prevalence of COPD and the first large gender-specific review.,These results will increase awareness of COPD as a critical woman’s health issue. | 1 |
Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD.,Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations.,Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported.,We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1.,We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD.,The patients were classified into groups with PA:A ≤1 and >1.,Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A >1.,The PA:A >1 group had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO2), lowest SpO2, highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations ≤1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results (P<0.05).,Predicted PA:A >1 was determined for SpO2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88-1).,SpO2 <90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07.,Lowest SpO2 during 6MWT may predict CT-measured PA:A, and lowest SpO2 <89% during 6MWT is excellent for detecting pulmonary hypertension in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex condition defined by progressive airflow limitation in response to noxious stimuli, inflammation, and vascular changes.,COPD exacerbations are critical events in the natural history of the disease, accounting for the majority of disease burden, cost, and mortality.,Pulmonary vascular disease is an important risk factor for disease progression and exacerbation risk.,Relative pulmonary artery enlargement on computed tomography scan, defined by a pulmonary artery to aortic (PA:A) ratio >1, has been evaluated as a marker of pulmonary vascular disease.,The PA:A ratio can be measured reliably independent of electrocardiographic gating or the use of contrast, and in healthy patients a PA:A ratio >0.9 is considered to be abnormal.,The PA:A ratio has been compared with invasive hemodynamic parameters, primarily mean pulmonary artery pressure in various disease conditions and is more strongly correlated with mean pulmonary artery pressure in obstructive as compared with interstitial lung disease.,In patients without known cardiac or pulmonary disease, the PA:A ratio is predictive of mortality, while in COPD, an elevated PA:A ratio is correlated with increased exacerbation risk, outperforming other well established predictors of these events.,Future studies should be aimed at determining the stability of the metric over time and evaluating the utility of the PA:A ratio in guiding specific therapies. | 1 |
Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD).,Our objectives were to assess the efficiency of combining RT with ET compared with ET alone.,We identified eligible studies through a systematic multi-database search.,One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility.,Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.,We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews.,The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity.,However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98).,In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone.,Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET. | Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients.,To date, however, there is no agreement for how long a rehabilitation program should be implemented.,In addition, current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients.,The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation (PR) program for COPD patients on pulmonary function, exercise capability, and body mass index (BMI).,A matched controlled trial was performed with outcome assessments evaluated at 6, 12, 18, 24, 30, and 36 months.,Eighty patients with moderate to severe COPD (age 63 ± 7 years; FEV1 48% ± 14) were recruited.,The control group received standard care only, while in addition, the case study group received PR for duration of three years.,These groups were matched for age, sex, BMI, FEV1% and number of pack-years smoked.,The decline in FEV1 after the three years was significantly lower in the PR group compared to control, 74 ml versus 149 ml, respectively (p < 0.001).,Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study, in contrast to the control group (p < 0.01).,A decreased BMI was noted in the control group after three years, while in the PR group a mild improvement was seen (p < 0.05).,Three years of outpatient pulmonary rehabilitation resulted in modifying the disease progression of COPD, as well as improving physical performance in these patients. | 1 |
BACKGROUND.,Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation.,This inflammation may persist even after smoking cessation and responds variably to corticosteroids.,Personalizing treatment to biologically similar “molecular phenotypes” may improve therapeutic efficacy in COPD.,IL-17A is involved in neutrophilic inflammation and corticosteroid resistance, and thus may be particularly important in a COPD molecular phenotype.,METHODS.,We generated a gene expression signature of IL-17A response in bronchial airway epithelial brushings from smokers with and without COPD (n = 238), and validated it using data from 2 randomized trials of IL-17 blockade in psoriasis.,This IL-17 signature was related to clinical and pathologic characteristics in 2 additional human studies of COPD: (a) SPIROMICS (n = 47), which included former and current smokers with COPD, and (b) GLUCOLD (n = 79), in which COPD participants were randomized to placebo or corticosteroids.,RESULTS.,The IL-17 signature was associated with an inflammatory profile characteristic of an IL-17 response, including increased airway neutrophils and macrophages.,In SPIROMICS the signature was associated with increased airway obstruction and functional small airways disease on quantitative chest CT.,In GLUCOLD the signature was associated with decreased response to corticosteroids, irrespective of airway eosinophilic or type 2 inflammation.,CONCLUSION.,These data suggest that a gene signature of IL-17 airway epithelial response distinguishes a biologically, radiographically, and clinically distinct COPD subgroup that may benefit from personalized therapy.,TRIAL REGISTRATION.,ClinicalTrials.gov NCT01969344.,FUNDING.,Primary support from the NIH, grants K23HL123778, K12HL11999, U19AI077439, DK072517, U01HL137880, K24HL137013 and R01HL121774 and contracts HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C and HHSN268200900020C. | Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge.,The prognostic significance of early readmission is not fully understood.,The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients.,The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge.,Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years.,Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity.,Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission.,The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59).,In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5).,In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. | 1 |
Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories.,The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients.,This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland.,The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices.,DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations.,Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items.,The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups.,The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them.,None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality.,The GOLD categories predict future risk inconsistently.,The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. | The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.,Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.,This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010).,Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest.,A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics.,Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.,Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year).,ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).,The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia. | 1 |
The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent.,Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent.,The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors.,Pathological changes in COPD are observed in central airways, small airways and alveolar space.,The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair.,Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70.,COPD is characterized by an accelerated decline in FEV1.,Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline.,The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy.,COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor.,Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support.,Lung volume reduction surgery and lung transplantation are advised in selected severe patients.,Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations. | Chronic obstructive pulmonary disease (COPD) is 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 |
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. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk.,However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed.,In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS.,Several studies sought out to determine the effects of withdrawing ICS in patients with COPD.,Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms.,However, these studies were fraught with numerous methodological limitations.,Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients.,Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol).,Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen.,Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice.,Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal.,In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice. | 1 |
The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown.,Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks.,We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure.,Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing.,Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified.,After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD.,The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung.,However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide.,Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease. | Early preclinical diagnosis of COPD is urgent.,We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases.,Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied.,It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients.,Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic.,The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFα, sTNF-RI, bFGF, TGF-β, IL-8).,Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography.,Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0.,In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established.,The amount of the arachidonic acid (20:4n-6) was increased by 13% (р < 0.05) in CB patients and by 41% (р < 0.001) in COPD patients, as compared with healthy persons.,The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased.,The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (р < 0.05) in CB patients and 2-fold (р < 0.001) in COPD patients.,The observed increase in the 20:4n-6/20:5n-3 ratio - 1.5-fold (р < 0.001) in CB patients and 3-fold in COPD patients - can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development.,Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids. | 1 |
Exacerbations largely determine the character of the progression and prognosis of chronic obstructive pulmonary disease (COPD).,Exacerbations are connected with changes in the microbiological landscape in the bronchi due to a violation of their immune homeostasis.,Many metabolic and immune processes involved in COPD progression are associated with bacterial colonization of the bronchi.,The objective of this review is the analysis of the molecular mechanisms of lipid metabolism and immune response disorders in the lungs in COPD exacerbations.,The complex role of lipid metabolism disorders in the pathogenesis of some infections is only beginning to be understood, however, there are already fewer and fewer doubts even now about its significance both in the pathogenesis of infectious exacerbations of COPD and in general in the progression of the disease.,It is shown that the lipid rafts of the plasma membranes of cells are involved in many processes related to the detection of pathogens, signal transduction, the penetration of pathogens into the cell.,Smoking disrupts the normally proceeded processes of lipid metabolism in the lungs, which is a part of the COPD pathogenesis. | The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown.,Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks.,We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure.,Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing.,Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified.,After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD.,The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung.,However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide.,Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease. | 1 |
Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk.,However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD).,TB and pneumonia have increased lung cancer risk.,The association between post-ICS pulmonary infections and lung cancer remains unclear.,We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database.,Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005.,Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use.,The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia.,For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia.,COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer.,Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions. | Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | 1 |
COPD is a common disease of the respiratory system.,Inflammation, cellular senescence and necroptosis are all pathological alterations of this disease, which may lead to emphysema and infection that aggravate disease progression.,Mitochondria acting as respiration-related organelles is usually observed with abnormal changes in morphology and function in CS-stimulated models and COPD patients.,Damaged mitochondria can activate mitophagy, a vital mechanism for mitochondrial quality control, whereas under the persistent stimulus of CS or other forms of oxidative stress, mitophagy is impaired, resulting in insufficient clearance of damaged mitochondria.,However, the excessive activation of mitophagy also seems to disturb the pathology of COPD.,In this review, we demonstrate the variations in mitochondria and mitophagy in CS-induced models and COPD patients and discuss the underlying regulatory mechanism of mitophagy and COPD, including the roles of inflammation, senescence, emphysema and infection. | Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function.,Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes.,NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD.,The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model.,A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours.,Cell viability was assessed by using XTT test.,Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry.,Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner.,Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone.,NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone.,NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation.,Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research. | 1 |
Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated.,The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence.,Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca.,We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups.,Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations.,Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS).,Overall, pneumologist adherence was 79.02%.,The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A.,Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy.,Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021).,ICS overprescription was the most common type of inappropriateness (17.81%).,Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004).,Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved.,Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important.,ICS represent the most prescribed overtreatment.,Further multicentric studies are needed to evaluate all factors that might influence the adherence rate. | Supplemental Digital Content is available in the text,To assess characteristics and outcomes of patients hospitalized with interstitial lung diseases (ILD) and to analyze patient's comorbidities, procedures, and in-hospital outcomes.,We identified patients hospitalized with idiopathic pulmonary fibrosis and others ILD such as hypersensitivity pneumonitis, cryptogenic organizing pneumonia, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, and sarcoidosis in Spain during 2014 and 2015.,We identified 14,565 discharges among patients admitted for ILD in Spain during the study period: idiopathic pulmonary fibrosis (IPF) in 42.32% (n = 6164), sarcoidosis in 37.65% (n = 5484), hypersensitivity pneumonitis in 10.55% (n = 1538), cryptogenic organizing pneumonia in 7.06% (n = 1028), pulmonary Langerhans cell histiocytosis in 1.48% (n = 215), and lymphangioleiomyomatosis in 0.94% (n = 136).,The most common associated comorbidities according to those included in the Charlson Comorbidity Index (CCI) were COPD, diabetes, and congestive heart disease.,The presence of pulmonary hypertension increased the probability of dying in patients with idiopathic pulmonary fibrosis (OR 1.36; 95%CI 1.06-1.73).,Patients with cryptogenic organizing pneumonia had the longest length of hospital stay and the highest percentage of hospital readmissions (23.64%).,The highest IHM corresponded to the idiopathic pulmonary fibrosis (14.94%).,Computed tomography of the chest was the procedure more used during admissions for ILD.,IPF was responsible for larger percentage of hospital admission among ILD in our study.,In addition, the IHM were higher in IPF patients in comparison with those with other ILD.,The most common associated comorbidity in ILD according to those included in the CCI was COPD.,Computed tomography of the chest was the procedure more frequently used. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by different phenotypes with either bronchial airways alterations or emphysema prevailing.,As blood biomarkers could be clinically useful for COPD stratification, we aimed at investigating the levels of blood biomarkers in COPD patients differentiated by phenotype: prevalent chronic airway disease versus emphysema.,In 23 COPD patients with prevalent airway disease (COPD-B), 22 COPD patients with prevalent emphysema (COPD-E), 9 control smokers (CSs), and 18 control nonsmokers (CNSs), we analyzed the expression levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay in plasma/serum; glutathione peroxidase and superoxide dismutase (SOD)-1 by immunochemical kits in plasma; and free F2-isoprostanes (F2-IsoPs) by gas chromatography in plasma.,F2-IsoPs level was increased in COPD-B and COPD-E compared with CSs and CNSs; in addition, CS showed higher levels than CNSs; SOD1 level was lower in COPD-B and COPD-E than that in CNSs.,Interestingly, MCP-1 level was higher only in COPD-E versus CSs and CNSs; EGF and IL-8 levels were higher in COPD-B and COPD-E versus CNSs; IL-6 level was increased in all three smoking groups (COPD-B, COPD-E, and CSs) versus CNS; IFN-γ and IL-1α levels were higher in CSs than in CNSs; and IL-1α level was also higher in CSs versus COPD-B and COPD-E.,In all subjects, F2-IsoPs level correlated positively and significantly with MCP-1, IL-2, IL-1β, IFN-γ, and TNF-α and negatively with SOD1.,When correlations were restricted to COPD-E and COPD-B groups, F2-IsoPs maintained the positive associations with IFN-γ, TNF-α, and IL-2.,We did not find any specific blood biomarkers that could differentiate COPD patients with prevalent airway disease from those with prevalent emphysema.,The MCP-1 increase in COPD-E, associated with the imbalance of oxidant/antioxidant markers, may play a role in inducing emphysema. | Grouping COPD subjects into clinical phenotypes might be useful for the management of the disease, but the clinical implications of such classification are still not totally clear, especially regarding prognosis.,The primary objective of this study was to assess whether the mortality rates were different between four predefined clinical phenotypes.,This is a retrospective, observational study carried out at the COPD clinic of a University Hospital.,A total of 891 COPD patients were classified, according to the Spanish COPD guidelines, into the following four phenotypes: asthma-COPD overlap (ACO; 75 subjects), nonexacerbator (NONEX; 531 subjects), exacerbator with chronic bronchitis (EXCB; 194 subjects), and exacerbator with emphysema (EXEMPH; 91 subjects).,We compared the mortality outcomes between the phenotypes.,After a follow-up of 48.4±25.2 months, there were 194 deaths (21.8%).,There were significant differences in all-cause mortality between phenotypes.,The ACO phenotype had the best long-term prognosis, whereas EXEMPH had the highest risk of death.,NONEX and EXCB mortality figures were in between the other two groups.,We also found some differences in the causes of death, and patients with EXEMPH were at a higher risk of dying because of COPD itself.,The differences in mortality did not seem related to the classification into phenotypes in itself but to disparities in COPD severity and comorbidity load between groups.,Classifying COPD patients according to several predefined clinical phenotypes can identify clusters of subjects with different mortality outcomes.,Some phenotypes are associated with a specific cause of death.,The mechanisms that underlie these differences seem to be related to COPD severity and comorbidities. | 1 |
Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines.,This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD.,Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis.,Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997-2001; (2) 2002-2006; and (3) 2007-2010.,Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression.,The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment.,Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis.,Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors.,In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens.,Predictors of initial therapy were identified. | Clinical audits have emerged as a potential tool to summarize the clinical performance of healthcare over a specified period of time.,However, the effectiveness of audit and feedback has shown inconsistent results and the impact of audit and feedback on clinical performance has not been evaluated for COPD exacerbations.,In the present study, we analyzed the results of two consecutive nationwide clinical audits performed in Spain to evaluate both the in-hospital clinical care provided and the feedback strategy.,The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation.,The first audit was performed from November-December 2008.,The feedback strategy consisted of personalized reports for each participant center, the presentation and discussion of the results at regional, national and international meetings and the creation of health-care quality standards for COPD.,The second audit was part of a European study during January and February 2011.,The impact of the feedback strategy was evaluated in term of clinical care provided and in-hospital survival.,A total of 94 centers participated in the two audits, recruiting 8,143 admissions (audit 1∶3,493 and audit 2∶4,650).,The initially provided clinical care was reasonably acceptable even though there was considerable variability.,Several diagnostic and therapeutic procedures improved in the second audit.,Although the differences were significant, the degree of improvement was small to moderate.,We found no impact on in-hospital mortality.,The present study describes COPD hospital care in Spanish hospitals and evaluates the impact of peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations.,It describes small to moderate improvements in the clinical care provided to COPD patients with no impact on in-hospital mortality. | 1 |
COPD is often associated with cardiovascular comorbidity.,Treatment guidelines recommend therapy with bronchodilators as first choice.,We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.,In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD.,Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score.,Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout.,All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators.,Consensus decisions were taken on every value and parameter.,The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.,Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol.,Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time.,The cardiac frequency was also significantly reduced in indacaterol-treated patients.,Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea.,These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency. | Decreased physical activity is associated with higher mortality in subjects with COPD.,The aim of this study was to assess clinical characteristics and physical activity levels (PALs) in subjects with COPD.,Seventy-three subjects with COPD (67 ± 7 yrs, 44 female) with one-second forced expiratory volume percentage (FEV1%) predicted values of 43 ± 16 were included.,The ratio of total energy expenditure (TEE) and resting metabolic rate (RMR) was used to define the physical activity level (PAL) (PAL = TEE/RMR).,TEE was assessed with an activity monitor (ActiReg), and RMR was measured by indirect calorimetry.,Walking speed (measured over 30-meters), maximal quadriceps muscle strength, fat-free mass and systemic inflammation were measured as clinical characteristics.,Hierarchical linear regression was applied to investigate the explanatory values of the clinical correlates to PAL.,The mean PAL was 1.47 ± 0.19, and 92% of subjects were classified as physically very inactive or sedentary.,The walking speed was 1.02 ± 0.23 m/s, the quadriceps strength was 31.3 ± 11.2 kg, and the fat-free mass index (FFMI) was 15.7 ± 2.3 kg/m2, identifying 42% of subjects as slow walkers, 21% as muscle-weak and 49% as FFM-depleted.,The regression model explained 45.5% (p < 0.001) of the variance in PAL.,The FEV1% predicted explained the largest proportion (22.5%), with further improvements in the model from walking speed (10.1%), muscle strength (7.0%) and FFMI (3.0%).,Neither age, gender nor systemic inflammation contributed to the model.,Apart from lung function, walking speed and muscle strength are important correlates of physical activity.,Further explorations of the longitudinal effects of the factors characterizing the most inactive subjects are warranted. | 1 |
Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires.,The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality.,Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology.,Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD. | Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation.,We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation.,COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily (tiotropium = 47, placebo = 44).,Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation.,Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit.,Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis.,For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration.,Patients (n = 46) had mean age of 67 years, mean baseline FEV1 of 0.84 L (33% predicted).,Mean (SE) increase in duration of activities (minutes during 2 weeks prior to each visit) from week 4 (prior to PR) to week 13 (end of PR) was 145 (84) minutes with tiotropium and 66 (96) minutes with placebo.,The increase from week 4 to week 25 (end of follow-up) was 262 (96) and 60 (93) minutes for the respective groups.,Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium.,No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant.,Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities. | 1 |
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension.,Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC), in forced expiratory volume (FEV1) over 0-12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 with MF/F versus F after 13 weeks of treatment.,Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ), symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.,The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 μg and MF/F 200/10 μg.,Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes), persisted for 12 hours after dosing, and were sustained over the 26-week treatment period.,Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 data were incorrectly collected after 2 days from the last dose of study treatment.,Improvements in SGRQ scores surpassed the minimum clinically important difference of more than four units with both MF/F treatments.,At 26 weeks, no notable between-treatment differences in the occurrence and nature of adverse events (AEs) were reported.,No unexpected AEs were observed.,Overall, 90 subjects reported AEs considered to be treatment-related, the most common of which were lenticular opacities, dysphonia, and oral candidiasis.,In conclusion, MF/F treatments improved lung function and respiratory health status, reduced exacerbations, and were well tolerated in subjects with moderate-to-very severe COPD. | 1 |
Cardiovascular disease is a major cause of morbidity and mortality in COPD patients.,Systemic inflammation associated with COPD, is often hypothesised as a causal factor. p38 mitogen-activated protein kinases play a key role in the inflammatory pathogenesis of COPD and atherosclerosis.,This study sought to evaluate the effects of losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, on vascular inflammation and endothelial function in chronic obstructive pulmonary disease (COPD) patients with systemic inflammation (defined by plasma fibrinogen >2·8g/l).,This was a randomised, double-blind, placebo-controlled, Phase II trial that recruited COPD patients with plasma fibrinogen >2.8g/l.,Participants were randomly assigned by an online program to losmapimod 7·5mg or placebo tablets twice daily for 16 weeks.,Pre- and post-dose 18F-Fluorodeoxyglucose positron emission tomography co-registered with computed tomography (FDG PET/CT) imaging of the aorta and carotid arteries was performed to quantify arterial inflammation, defined by the tissue-to-blood ratio (TBR) from scan images.,Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD).,We screened 160 patients, of whom, 36 and 37 were randomised to losmapimod or placebo.,The treatment effect of losmapimod compared to placebo was not significant, at -0·05 for TBR (95% CI: -0·17, 0·07), p = 0·42, and +0·40% for FMD (95% CI: -1·66, 2·47), p = 0·70.,The frequency of adverse events reported was similar in both treatment groups.,In this plasma fibrinogen-enriched study, losmapimod had no effect on arterial inflammation and endothelial function at 16 weeks of treatment, although it was well tolerated with no significant safety concerns.,These findings do not support the concept that losmapimod is an effective treatment for the adverse cardiovascular manifestations of COPD. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 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