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Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p

Long-acting bronchodilators represent the mainstay of maintenance treatment of chronic obstructive pulmonary disease (COPD). This state-of-the-art review summarizes currently available data on the safety, efficacy, and clinical effectiveness of long-acting bronchodilators and describes their role in the management of COPD, as defined by current national and international guidelines. Data from extensive clinical trials and real-life studies have demonstrated that long-acting beta-2 agonists and long-acting muscarinic antagonists can safely reduce the frequency of exacerbations, alleviate symptoms, and improve quality of life, exercise tolerance, and lung function of patients with COPD. They are recommended as first-line maintenance treatment of COPD.

Background The relationship between respiratory diseases and individual cardiovascular diseases, and the impact of cardiovascular diseases on mortality in patients with respiratory disease, are unclear. Objectives This study sought to determine the relationship between chronic obstructive pulmonary disease (COPD), asthma and interstitial lung disease (ILD), and individual cardiovascular diseases, and evaluate the impact of individual cardiovascular diseases on all-cause mortality in respiratory conditions. Methods The authors conducted a cohort study of all patients admitted to 7 National Health Service hospitals across the North West of England, between January 1, 2000, and March 31, 2013, with relevant respiratory diagnoses, with age-matched and sex-matched control groups. Results A total of 31,646 COPD, 60,424 asthma, and 1,662 ILD patients were included. Control groups comprised 158,230, 302,120, and 8,310 patients, respectively (total follow-up 2,968,182 patient-years). COPD was independently associated with ischemic heart disease (IHD), heart failure (HF), atrial fibrillation, and peripheral vascular disease, all of which were associated with all-cause mortality (e.g., odds ratio for the association of COPD with HF: 2.18 [95% confidence interval (CI): 2.08 to 2.26]; hazard ratio for the contribution of HF to mortality in COPD: 1.65 [95% CI: 1.61 to 1.68]). Asthma was independently associated with IHD, and multiple cardiovascular diseases contributed to mortality (e.g., HF hazard ratio: 1.81 [95% CI: 1.75 to 1.87]). ILD was independently associated with IHD and HF, both of which were associated with mortality. Patients with lung disease were less likely to receive coronary revascularization. Conclusions Lung disease is independently associated with cardiovascular diseases, particularly IHD and HF, which contribute significantly to all-cause mortality. However, patients with lung disease are less likely to receive coronary revascularization.

Background: SLS COPD was the first open-label randomised controlled trial demonstrating a reduction in moderate/severe COPD exacerbations with once-daily inhaled fluticasone furoate/vilanterol (FF/VI) in everyday clinical practice. Here we report FF/VI effectiveness and safety in predefined patient subgroups. Methods: Patients with COPD, exacerbation history, and receiving maintenance inhaler therapy, were randomised to initiate FF/VI 100/25 μg or continue usual care (UC) with 12 months’ follow-up. Annual rates of moderate/severe exacerbations (primary outcome), selected secondary outcomes, and incidence of pneumonia serious adverse events of special interest (SAESI) were compared between randomisation groups across various patient subgroups/baseline treatment strata. SAESI rates by actual treatment were also assessed. Results: Lower exacerbation rates were observed for FF/VI versus UC across all subgroups/strata, including ICS + LABA therapy subset (8.0% [0.1, 15.4]), except in patients without baseline airflow limitation (−0.5% [–29.8, 22.1]). Larger reductions compared to the overall analysis were observed for patients on ICS-containing regimens (excluding LAMA) before the study (15.6% [3.4, 26.3]), and with baseline CAT score

Background COPD is a leading cause of mortality. Research Question We hypothesized that applying machine learning to clinical and quantitative CT imaging features would improve mortality prediction in COPD. Study Design and Methods We selected 30 clinical, spirometric, and imaging features as inputs for a random survival forest. We used top features in a Cox regression to create a machine learning mortality prediction (MLMP) in COPD model and also assessed the performance of other statistical and machine learning models. We trained the models in subjects with moderate to severe COPD from a subset of subjects in Genetic Epidemiology of COPD (COPDGene) and tested prediction performance in the remainder of individuals with moderate to severe COPD in COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared our model with the BMI, airflow obstruction, dyspnea, exercise capacity (BODE) index; BODE modifications; and the age, dyspnea, and airflow obstruction index. Results We included 2,632 participants from COPDGene and 1,268 participants from ECLIPSE. The top predictors of mortality were 6-min walk distance, FEV1 % predicted, and age. The top imaging predictor was pulmonary artery-to-aorta ratio. The MLMP-COPD model resulted in a C index ≥ 0.7 in both COPDGene and ECLIPSE (6.4- and 7.2-year median follow-ups, respectively), significantly better than all tested mortality indexes (P Interpretation An MLMP-COPD model outperformed four existing models for predicting all-cause mortality across two COPD cohorts. Performance of machine learning was similar to that of traditional statistical methods. The model is available online at: https://cdnm.shinyapps.io/cgmortalityapp/.

BackgroundAsthma and COPD diagnoses are used to classify chronic airway diseases; however, both diseases are related to phenotypic traits like allergy, obesity, cough, sputum production, low-grade inflammation, smoking, elevated blood eosinophil count, comorbidities, and occupational exposures. Whether such traits can replace asthma and COPD diagnoses when assessing risk of exacerbation is unclear. We tested the hypothesis that individuals with either asthma or COPD diagnoses have similar risk of moderate and severe exacerbations when adjusted for differences in phenotypic traits.MethodsFrom the Copenhagen General Population Study, a cohort study of the general population, we included 7190 individuals with chronic airway disease. Phenotypic traits were recorded at baseline and risk of exacerbations was assessed during follow-up from 2003 to 2013.ResultsThe incidence rate ratio (IRR) of moderate exacerbations in individuals with clinical COPD was 1.61 (95% Confidence Interval, 1.27–2.02) compared to individuals with asthma in a model only adjusted for age, sex, and education, but after the inclusion of phenotypic traits IRR was 1.05 (0.82–1.35). Corresponding IRRs of severe exacerbations in individuals with clinical COPD versus asthma were 3.82 (2.73–5.35) and 2.28 (1.63–3.20), respectively.ConclusionsWhen taking phenotypic traits into account, individuals with asthma and COPD had comparable risk of moderate exacerbations; however, corresponding risk of severe exacerbations was higher in individuals with COPD than in those with asthma.

Background: Investigation of the natural history of chronic obstructive pulmonary disease (COPD) has led to the recognition that individuals with higher than normal lung function may have lower risk of developing COPD. We tested the hypothesis that individuals with supernormal lung function have lower risk of COPD. Methods: We followed 108,246 adults from the Copenhagen General Population Study recruited between 2003 and 2015 for clinical COPD outcomes until 2018. A subset of 16,892 attended another examination approximately 10 years later, allowing to investigate lung function decline and COPD development (forced expiratory volume in 1 se (FEV1)/forced vital capacity (FVC)upper limit of normal (ULN). Findings: At baseline, 3944(4%) had supernormal lung function, 91,938(85%) normal lung function, and 12,364(11%) had below normal lung function. Individuals with baseline supernormal versus normal lung function had higher FEV1 decline but did not differ in FEV1/FVC decline. None had COPD at 10 years in those with supernormal lung function, while 3% had in those with normal lung function. Early-life risk factors associated with COPD development and smoking exposure in different stages of life were less common in individuals with supernormal lung function. Compared to individuals with normal lung function, multivariable adjusted hazard ratios in those with supernormal lung function were 0·19(95% confidence interval:0·08–0·46) for acute obstructive lung disease hospitalisations, 0·56(0·45–0·69) for pneumonia hospitalisations, and 0·81(0·72–0·91) for all-cause mortality. Interpretation: Supernormal lung function is associated with lower risk of developing COPD. Funding: Herlev and Gentofte Hospital and Lundbeck Foundation.

Rationale Pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been thoroughly assessed in patients with moderate airflow limitation. Objectives To determine the incidence of pneumonia and risk factors in COPD patients with moderate airflow limitation who had, or were at high risk for cardiovascular disease. Methods In the Study to Understand Mortality and MorbidITy in COPD (SUMMIT), 16,590 subjects with moderate airflow limitation (50% ≤ FEV1 ≤ 70% predicted) and heightened cardiovascular risk were randomized double-blind 1:1:1:1 to inhaled once-daily vilanterol 25 μg (VI), fluticasone furoate 100 μg (FF), vilanterol 25 μg combined with 100 μg fluticasone furoate (FF/VI), or matched placebo. In a pre-specified analysis, we assessed investigator-reported adverse pneumonia events, and independently-adjudicated fatal events. Measurements and main results The safety population comprised 16,568 subjects who actually received study medication. There were 1017 pneumonia events reported from 842 subjects. For placebo, FF, VI and FF/VI, reported pneumonia incidence was 5%, 5%, 4% and 6%, respectively. When adjusted for time on treatment, event rates were similar in the placebo, FF and FF/VI containing arms (3.84, 4.24 and 3.95/100 treatment years, respectively) but lower in the VI group (2.77/100 treatment years). Risk factors for pneumonia risk included: greater degree of airflow limitation (i.e. FEV1 2. Conclusions In contrast to previous studies in patients with severe disease, increased pneumonia risk with inhaled corticosteroid use was not evident in COPD subjects with moderate airflow limitation and heightened cardiovascular risk.

Resumen Este resumen ejecutivo del Informe de 2017 de la Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) se basa principalmente en las modificaciones y novedades del documento anterior. Los cambios mas destacados incluyen: a) se ha diferenciado entre la exploracion espirometrica y la de los sintomas para evaluar la enfermedad pulmonar obstructiva cronica (EPOC). En la propuesta actual, los grupos ABCD se refieren exclusivamente a sintomas y antecedentes de exacerbaciones de los pacientes; b) para cada uno de los grupos, se proponen estrategias de intensificacion de los tratamientos farmacologicos; c) se introduce el concepto de reduccion escalonada de la terapia en el esquema de evaluacion del tratamiento; d) se detalla mas extensamente el tratamiento no farmacologico; y, f) se revisa la importancia de las diferentes co-morbilidades en lo que respecta al tratamiento de la EPOC.

Long-term prognosis of patients with characteristics of both chronic obstructive pulmonary disease (COPD) and asthma, named asthma-COPD overlap, is poorly described. We investigated the long-term prognosis of individuals with different types of chronic airway disease, with a special focus on individuals with asthma-COPD overlap.We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those with asthma-COPD overlap with asthma onset before the age of 40 years, and those with asthma-COPD overlap with asthma onset after the age of 40 years. We defined asthma-COPD overlap as current self-reported asthma and a postbronchodilatatory forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio of less than 0·7, without any restrictions regarding smoking. We investigated the course of FEV1 decline for 18 years and risk of admission to hospital due to exacerbations or pneumonias and respiratory and all-cause mortality for 22 years. We analysed FEV1 decline in the six groups using a linear mixed-effects model.We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma. The multivariable-adjusted decline in FEV1 in asthma-COPD overlap with early-onset asthma was 27·3 mL (standard error 5·0) per year, which did not differ significantly from the decline of 20·9 mL (1·2) per year in healthy never-smokers (p=0·19). FEV1 decline in individuals with asthma-COPD overlap with late-onset asthma was 49·6 mL (3·0) per year, higher than the decline in asthma-COPD overlap with early-onset asthma (p=0·0001), the decline of 39·5 mL (2·5) per year in COPD (p=0·003), and the decline in healthy never-smokers (p0·0001). Hazard ratios for hospital admissions due to exacerbations of asthma or COPD were 39·48 (95% CI 25·93-60·11) in asthma-COPD overlap with early-onset asthma, 83·47 (61·67-112·98) in asthma-COPD overlap with late-onset asthma, 23·80 (17·43-33·50) in COPD, and 14·74 (10·06-21·59) in asthma compared with never-smokers without lung disease (all p0·0001). Life expectancy was 9·3 years (5·4-13·1) shorter in participants with asthma-COPD overlap with early-onset asthma, 12·8 years (11·1-14·6) shorter in those with asthma-COPD overlap with late-onset asthma, 10·1 years (8·6-11·5) shorter in those with COPD (all p0·0001), and 3·3 years (1·0-5·5) shorter in those with asthma (p=0·004) than in healthy never-smokers.Prognosis of individuals with asthma-COPD overlap is poor and seems to be affected by the age of recognition of asthma, being worst in those with late asthma onset (after 40 years of age). Such patients should be followed up closely to prevent fast lung function decline and exacerbations.Capital Region of Copenhagen, Danish Heart Foundation, Danish Lung Foundation, Velux Foundation, AstraZeneca.

Background There is insufficient evidence about the long-term course of depressive symptom trajectories and their impact among patients with COPD. Methods We analysed 3-year data obtained from patients with COPD participating in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. Patients were split into four groups on the basis of Center for Epidemiologic Studies Depression Scale score ( Results A total of 1,589 patients with COPD completed the 3-year follow-up. Of these, 55% (n = 869) were classified as never depressed, 24% (n = 377) were classified as persistently depressed, 14% (n = 226) developed new onset of depression, and 7% (n = 117) had depression that remitted. Female sex and history of stroke were associated with substantial increases in the odds of persistent depression (OR, 2.95; 95% CI, 2.05-4.24 and OR, 3.09; 95% CI, 1.43-6.67, respectively). Odds of new onset depression increased with worse health status (OR, 1.10; 95% CI, 1.04-1.17 per 4-point increase in St. George's Respiratory Questionnaire score) and moderate to severe dyspnea (OR, 1.57; 95% CI, 1.07-2.31 for modified Medical Research Council score ≥ 2 vs 0 or 1). During follow-up, patients with persistent or new-onset depression experienced more exacerbations and more pronounced loss in performance as assessed by reduction in the 6-min walk distance (6MWD) test score. Conclusions About one in four patients with COPD had persistent depressive symptoms over 3 years. Clinicians should be aware of the characteristics of persistent and new onset depressive symptoms, which are associated with risk of exacerbations and loss of performance on the 6MWD test. Interventions that ameliorate the course of depression are needed. Trial Registry ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov.

Exacerbations of respiratory symptoms occur frequently and are responsible for much of the morbidity associated with chronic obstructive pulmonary disease (COPD).1 Not all patients with COPD experience exacerbations, but some patients experience frequent exacerbations of their disease.2 One of the main goals of COPD management is to reduce exacerbations, and several drugs have been shown to reduce the number of exacerbations in patients at risk.1 Most of the evidence base for reducing the risk of exacerbations comes from carefully planned efficacy trials in narrowly defined populations, with the 2016 effectiveness trial, The Salford Lung Study, as a notable exception.

OBJECTIVE: Exacerbations of COPD requiring hospital admission have important clinical and societal implications. We sought to investigate the incidence, recurrence, risk factors, and mortality of patients with COPD exacerbations requiring hospital admission compared with those without hospital admission during 3-year follow-up. Patients with COPD (N = 2,138) were identified from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) observational cohort. METHODS: An analysis of time to first event of hospital admission was performed using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders. RESULTS: Of the 2,138 patients, 670 (31%) reported a total of 1,452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio, 2.71; 95% CI, 2.24-3.29; P P CONCLUSIONS: Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. Patients with COPD at a high risk for hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov

Summary Background COPD patients with chronic bronchitis include a subgroup with persistent sputum production on most or every day. We hypothesized that COPD patients with persistent sputum production have a different profile of airway inflammation, and more severe clinical characteristics. Objective To compare the airway inflammation profile and clinical characteristics of COPD persistent and non-persistent sputum producers. Methods COPD persistent sputum producers ( n = 26) and non-persistent sputum producers ( n = 26) underwent sputum induction and pulmonary function tests. Exacerbation history was recorded; the St. George's Respiratory Questionnaire, Modified Medical Research Council Dyspnoea scale and COPD Assessment Tool were completed. 33 COPD patients provided sputum for bacteriology. Results Persistent sputum producers had lower post-bronchodilator FEV 1 % predicted ( p = 0.01), diffusion capacity ( p = 0.04), 6 min walk test distance ( p = 0.05), and higher closing volume ( p = 0.01), BODE index ( p = 0.01), rate of bacterial colonization ( p = 0.004) and exacerbations ( p = 0.03) compared to non-persistent sputum producers. The mean SGRQ and CAT scores were higher in persistent sputum producers ( p = 0.01 and 0.03 respectively). Sputum neutrophil and eosinophil total cell counts were higher in persistent sputum producers ( p = 0.02 and 0.05 respectively). Sputum levels of eotaxin ( p = 0.02), MCP-1 ( p = 0.02), TNF-α ( p = 0.03) and IL-6 ( p = 0.05) were higher in persistent sputum producers. Conclusion COPD persistent sputum producers have more severe clinical characteristics and increased concentrations of some inflammatory mediators in the airways.

Study objectives: The aim of this analysis was to understand the implications of the GOLD 2011 multidimensional system for the assessment and management of COPD, using data from a real-world observational study. Methods: Data were drawn from the Adelphi Respiratory Disease Specific Programme, a cross-sectional survey of consulting patients in five European countries and in the US undertaken between June and September 2011. Patients were classified using both the GOLD 2010 and revised GOLD 2011 criteria, and profiled with regards to demographics, disease characteristics and treatment patterns. Results: Information on 3813 COPD patients was collected. Disease characteristics showed a general tendency to worsen in parallel with worsening of symptoms. When comparing dual versus single risk criteria, the inclusion of exacerbation history resulted in an increase in the number of patients in high risk groups. The highest proportions of patients receiving inhaled corticosteroids (ICS) were in group D. However, a considerable proportion of patients in low risk groups were receiving ICS/long-acting beta(2) agonists. Conclusions: Our analysis confirmed the relationship between higher symptomatic burden, increased airflow limitation and exacerbation, and further illustrated the importance of including exacerbation history in the assessment of COPD to identify patients at high risk. As based on data from current clinical practice, this study also highlighted the frequent and potentially inappropriate use of ICS and bronchodilators in patients at low risk of experiencing exacerbations. (C) 2014 Elsevier Ltd. All rights reserved. Study objectives The aim of this analysis was to understand the implications of the GOLD 2011 multidimensional system for the assessment and management of COPD, using data from a real-world observational study. Methods Data were drawn from the Adelphi Respiratory Disease Specific Programme, a cross-sectional survey of consulting patients in five European countries and in the US undertaken between June and September 2011. Patients were classified using both the GOLD 2010 and revised GOLD 2011 criteria, and profiled with regards to demographics, disease characteristics and treatment patterns. Results Information on 3813 COPD patients was collected. Disease characteristics showed a general tendency to worsen in parallel with worsening of symptoms. When comparing dual versus single risk criteria, the inclusion of exacerbation history resulted in an increase in the number of patients in high risk groups. The highest proportions of patients receiving inhaled corticosteroids (ICS) were in group D. However, a considerable proportion of patients in low risk groups were receiving ICS/long-acting β 2 agonists. Conclusions Our analysis confirmed the relationship between higher symptomatic burden, increased airflow limitation and exacerbation, and further illustrated the importance of including exacerbation history in the assessment of COPD to identify patients at high risk. As based on data from current clinical practice, this study also highlighted the frequent and potentially inappropriate use of ICS and bronchodilators in patients at low risk of experiencing exacerbations.

Chronic obstructive pulmonary disease (COPD) is currently defined as a common preventable and treatable disease that is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association with prognosis or response to therapy, the most notable being the feature of frequent exacerbations.

Introduction Aucune etude n’a examine les consequences cliniques du retrait des bronchodilatateurs a longue duree d’action (LABA) ou des corticosteroides inhales (CSI) malgre les implications potentielles tant pour la pratique clinique que pour la conception des essais cliniques. SUMMIT offre une occasion unique d’examiner l’impact de l’utilisation et du retrait de medicaments anterieurs a l’etude sur le risque de mortalite et sur les exacerbations de BPCO apres randomisation. Methodes SUMMIT est le plus grand essai de survie chez les patients atteints de BPCO et avec un risque cardiovasculaire accru, randomisant plus de 16 000 patients pour recevoir une fois par jour CSI seul (Furoate de fluticasone-FF), LABA seul (vilanterol-VI), CSI/LABA (FF/VI) ou placebo. Les patients ont ete repartis en 4 groupes selon le traitement avant la randomisation : aucun (aucun traitement anterieur, n = 9423), CSI seul ( n = 643), bronchodilatateur longue duree d’action (antagoniste muscarinique ou beta-agoniste) seul ( n = 1734) et CSI/BDLA ( n = 4617). L’analyse post-hoc du delai de survenue du deces et de la premiere exacerbation moderee/severe a ete realisee a l’aide de modeles de risques proportionnels de Cox. Resultats La demographie etait similaire dans les 4 groupes a celle de la population globale [1] a l’exception de la frequence d’une exacerbation au cours de l’annee precedant l’etude (plus eleve dans le groupe CSI seul, 65 % contre 33–49 %). Le Tableau 1 montre la difference des risques de deces et d’exacerbations dans les bras actifs en comparaison au placebo, au sein de chaque sous-groupe defini en fonction des traitements anterieurs et du traitement pendant l’essai. Il n’y a eu aucun effet sur la mortalite ou les exacerbations de BPCO dans les 4 groupes. Conclusion Dans ce large essai clinique randomise, il n’y a eu aucun impact du retrait de CSI ou de BDLA sur les effets ulterieurs de ces medicaments sur la mortalite et le risque d’exacerbations.

Background: Whether the combination of a once-daily inhaled corticosteroid with a once-daily longacting β 2 agonist is more protective than a once-daily longacting β 2 agonist alone against exacerbations of chronic obstructive pulmonary disease (COPD) is unknown. We hypothesised that fluticasone furoate and vilanterol would prevent more exacerbations than would vilanterol alone. Methods: We did two replicate double-blind parallel-group 1 year trials. Both studies began on Sept 25, 2009. Study 1 ended on Oct 31, 2011, and study 2 on Oct 17, 2011. Eligible patients were aged 40 years or older, had a history of COPD, a smoking history of 10 or more pack-years, a ratio of forced expiratory volume in 1 s (FEV 1) to forced vital capacity of 0·70 or less after bronchodilators (and an FEV 1 of 70% or less of predicted), and a documented history of one or more moderate or severe disease exacerbations in the year before screening. Patients were randomly assigned (1:1:1:1) on the basis of the Registration and Medication Ordering System to 25 μg vilanterol alone or 25 μg vilanterol combined with either 50 μg, 100 μg, or 200 μg fluticasone furoate once daily. Our primary endpoint was the yearly rate of moderate and severe exacerbations. The trials were analysed separately and a pooled analysis was also done. These trials are registered with ClinicalTrials.gov (NCT01009463 and NCT01017952). Findings: 1622 patients in study 1 and 1633 patients in study 2 were randomly assigned. In study 1, no significant difference in exacerbation rate was noted between the 200/25 μg fluticasone furoate/vilanterol group and the vilanterol only group (mean 0·90 events vs 1·05 events per year; ratio 0·9 [95% CI 0·7-1·0]). Because of the statistical hierarchy used, we could not infer significance for the 50 μg and 100 μg groups. In study 2, significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group (p=0·0398 for the 50 μg group, 0·0244 for the 100 μg group, and 0·0004 for the 200 μg group). In the pooled analysis, significantly fewer moderate and severe exacerbations were noted in all fluticasone furoate/vilanterol groups than in the vilanterol only group (0·0141 for the 50 μg group

Summary Objectives To evaluate regional differences in and risk factors for admission, length of stay, mortality, and readmission for community-acquired pneumonia in elderly Danish patients. Methods National registry study on elderly Danish citizens with an acute admission in 2009 owing to community-acquired pneumonia. We studied differences among hospitals in length of stay, in-hospital mortality, mortality within 30 days of discharge, and readmission within 30 days after discharge using Cox regression models with adjustments for age, sex, ventilatory support, and co-morbidity by Charlson's index score. Results A total of 11,332 elderly citizens were admitted with community-acquired pneumonia. Mortality during admission and 30-days from discharge were 11.6% and 16.2%, respectively. Readmission rates within 30 days of discharge were 12.3%. There were significantly differences between hospitals in length of stay. A high Charlson index score and advanced age were significantly risk factors for death during admission and within 30 days of discharge. Male sex and high Charlson index score were significant risk factors for readmission. Admission to large bed capacity hospital was a significant risk factor for death and readmission within 30 days of discharge. Conclusions Length of stay, rate of admission, mortality and readmission in elderly Danish patients with community-acquired pneumonia follows international findings. There are regional differences between hospitals. In depth investigation in regional differences could reveal potential feasible clinical interventions with an improvement of readmission-, mortality rates and cost.

BACKGROUND: Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test (6MWT). To improve the utility of the 6MWT for patient and health care system management, the interpretation of the functional status measure in relation to death and hospitalization should be elucidated. METHODS: Three-year, prospective, multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD. RESULTS: We measured 6MWD at baseline and annually in 2110 patients with clinically stable Global Initiative for Obstructive Lung Disease (GOLD) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality. During the study, 200 patients died and 650 were hospitalized. Using receiver operating characteristics, the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization (area under the curve 0.67 and 0.60 respectively); however, the discriminatory thresholds, especially for mortality, were influenced by age. The mean (SE) 6MWD declined by 1.6 (1.2) m per year in GOLD II, 9.8 (1.3) m per year in GOLD III, and 8.5 (2.4) m per year in GOLD IV. CONCLUSION: The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD.

SummaryObjectiveWe hypothesize that airflow limitation is associated with increasing arterial stiffness and that having COPD increases a non-invasive measure of arterial stiffness – the aortic augmentation index (AIx) – independently of other CVD risk factors.MethodsThis population study is based on 3374 subjects from the Copenhagen City Heart Study; 494 had COPD. We used multiple linear regression analyses to examine the association between COPD and AIx adjusted for CVD risk factors. Furthermore, we analyzed the association between AIx and FEV1, FVC and FEV1/FVC in the entire population.ResultsAIx was higher in subjects with COPD than in subjects without: 25.7 vs. 21.0 (p

Summary Background The National Institute for Health and Clinical Excellence (NICE) COPD 2004 guidelines recommend: ∗ COPD patients who smoke should be encouraged to stop at every opportunity; ∗ Inhaled corticosteroid should be used only among patients with moderate to severe COPD; ∗ Pharmacists should identify smokers and provide smoking cessation advice. The community pharmacy contract requires pharmacists to review patients’ medications, creating an opportunity for reviewing the prescribing of inhaled corticosteroids in COPD. The survey explored the degree to which community pharmacists in North West England identify and provide advice to smokers and assess prescribed inhaled corticosteroids among COPD patients. Methods A self-completion questionnaire was sent to 2080 community pharmacists from the 2005 pharmacist census database. Results Of the 1051 (50.5%) respondants, 37.1% mentioned COPD as a risk from smoking most or every time and 54.5% sometimes or rarely, and 19.6% routinely asked about smoking status when dispensing COPD medication. Pharmacists with more than 20 years experience were more likely to have read the Guideline compared to pharmacists with 10 years or less (OR: 1.54; 95% CI: 1.13 to 2.10). Pharmacists who had read the NICE Guideline (46.8%) were around twice as likely to mention COPD as a risk of smoking, ask about COPD if inhaled corticosteroids were dispensed and ask about smoking routinely if COPD medication was dispensed. (p Conclusion The NICE guidelines on COPD encourage community pharmacists to carry out smoking cessation and educational interventions, but further support is needed.

Introduction Les β2 agonistes de longue duree d’action (LABA), les corticoides inhales (CSI) et leur association diminuent les exacerbations dans la BPCO (EBPCO) chez les patients ayant une obstruction chronique severe des voies aeriennes (OCVA). Leur efficacite dans la reduction d’EBPCO chez les patients avec une OCVA moderee demeure incertaine ( Fig. 1 ). Methodes Summit (Study to Understand Mortality and Morbidity) etude multicentrique randomisee controlee en double-aveugle chez 16 485 patients (40–80 ans) avec une BPCO moderee qui etaient a risque eleve de maladie cardiovasculaire. Les traitements inhales quotidiens etaient : placebo (n = 4 111), vilanterol [VI] 25 μg ; n = 4 118, furoate de fluticasone [FF] 100 μg ; n = 4 135 et l’association (FF 100 μg + VI 25 μg [FF/VI]) ; n = 4 121. L’impact sur les EBPCO moderees/severes etait un autre objectif predefini. Resultats Les participants etaient principalement des hommes (75 %) d’âge moyen 65 ± 8 ans avec 47 % de fumeurs actifs et une moyenne de VEMS de 60 % de la valeur predite (54–65 %). Dans l’annee precedant l’inclusion, 39 % des patients ont eu une EBPCO et 15 % deux ou plus. La mortalite toute cause (critere principal) n’a pas ete affectee par l’un des traitements. Versus placebo, le risque d’une premiere EBPCO a diminue avec FF/VI (HR 0,80, IC 95 % 0,73 ; 0,86) et VI (HR 0,91, IC 95 % 0,84 ; 0,99), mais pas avec FF (HR 0,97, IC 95 % 0,90 ; 1,05) ( Fig. 1 ). Tous les traitements ont conduit a une diminution du taux d’EBPCO moderees/severes (FF/VI 29 % [22 ; 35], VI 10 % [2 ; 10], et FF 12 % [4 ; 19]). Des resultats similaires ont ete rapportes sur le delai d’apparition de la 1re EBPCO necessitant des hospitalisations et le taux. Dans une analyse post hoc, FF/VI a augmente le delai d’apparition de la 1re EBPCO moderee ou severe vs placebo dans une mesure similaire chez des patients avec un VEMS Conclusion Chez les patients avec une OCVA moderee, FF/VI conduit a une diminution du risque d’EBPCO moderee/severe et de son taux. Un effet similaire a ete rapporte pour les EBPCO necessitant une hospitalisation. Les effets etaient similaires chez les patients avec un VEMS Financements Finance par GSK 113782 ( NCT01313676 ).

Objective: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD.Methods: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300 mu g or placebo twice daily via Turbuhaler (R) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment.Results: Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n = 33) or placebo (n = 32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV(1) (AZD4818-placebo: 0.026 L, p = 0.69), morning PEF (-6 L/min, p = 0.23), or other lung function measures. There was no difference between treatment groups in the 6-min walk test, MMRC dyspnoea index, BODE index and CCQ scores. Plasma concentrations indicated that patients were exposed to AZD4818 as expected. AZD4818 was well tolerated: 27 treatment-related adverse events (13 with AZD4818, 14 with placebo), 2 serious adverse events (both AZD4818: exacerbation [considered not treatment-related] and deep vein thrombosis [considered treatment-related]) and 11 discontinuations (7 with AZD4818).Conclusions: Inhaled AZD4818 was well tolerated at 300 mu g twice daily for 4 weeks in patients with COPD; however, there was no indication of a beneficial treatment effect despite exposure as expected. These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas. (C) 2010 Elsevier Ltd. All rights reserved.

BACKGROUND: The 6-min walking test (6MWT) is widely used to assess exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Given the prognostic significance of the 6MWT, it is important to identify why some COPD patients perform poorly in terms of this outcome. We aimed to identify clinical determinants of a poor 6-min walking distance (/=2) are significant clinical determinants of poor 6MWD performance (

BackgroundAnxiety and dyspnea, 2 major symptoms in patients with chronic obstructive pulmonary disease (COPD), are associated with high morbidity and mortality. Thus, critically evaluating and synthesizing the existing literature employing pulmonary rehabilitation (PR) and other behavioral therapies in the treatment of anxiety and dyspnea in patients with COPD may help clinicians determine the most efficacious potential treatments. We aim to examine the efficacy of PR and behavioral therapy [eg, cognitive behavioral therapy (CBT) and counseling] and other adjunct modalities used in patients with COPD.MethodsWe extracted relevant studies searching the published literature using an electronic database CINAHL, Medline, PubMed, Science Direct, and the Web of Science was conducted (spanning January 1, 2006 to November 15, 2016). Studies were included if they conducted PR and behavioral therapy (CBT, self-management, yoga) to treat anxiety and/or dyspnea in patients with COPD with or without randomized controlled trial.ResultsThe 47 studies selected included 4595 participants (PR = 3756 and behavioral therapy = 839), ranging in age from 58 to 75 years. The total number of participants receiving a treatment was 3928, and 667 participants served in control groups. In the majority of studies, PR and CBT are effective in the treatment of anxiety and dyspnea in the short term, but the long-term benefit is limited. In addition, self-management, yoga therapy, and CBT plus PR were beneficial.ConclusionsPR and CBT reduced both anxiety and dyspnea symptoms in patients with COPD in the short term. However, maintenance programs and the long-term benefits of PR and CBT remain inconclusive. Generally, the studies were relatively small and uncontrolled. Thus, prospective and randomized controlled trials with larger sample sizes are needed.

Background Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study. Methods A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 μg), FP (500 μg), or SFC (SAL 50 μg/FP 500 μg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded. Results At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was −3.1% for placebo, −1.7% for SAL, −2.9% for FP, and −3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, −0.3%, and −0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%). Conclusions Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo. Trial registration ClinicalTrials.gov Identifier: NTC00268216

The authors of previous reports have suggested that women are more susceptible to cigarette smoke and to an airway-predominant COPD phenotype rather than an emphysema-predominant COPD phenotype. The purpose of this study was to test for sex differences in COPD phenotypes by using high-resolution CT (HRCT) scanning in male and female smokers with and without COPD.All subjects completed spirometry and answered an epidemiologic respiratory questionnaire. Inspiratory HRCT scans were obtained on 688 smokers enrolled in a family-based study of COPD. Emphysema was assessed by using a density mask with a cutoff of -950 Hounsfield units to calculate the low-attenuation area percentage (LAA%) and by the fractal value D, which is the slope of a power law analysis defining the relationship between the number and size of the emphysematous lesions. Airway wall thickness was assessed by calculating the square root of the airway wall area (SQRTWA) and the percentage of the total airway area taken by the airway wall (WA%) relative to the internal perimeter.Women had a similar FEV(1) (women, 65.5% +/- 31.9% predicted; men, 62.1% +/- 30.4% predicted; p = 0.16) but fewer pack-years of cigarette smoking (women, 37.8 +/- 19.7 pack-years; men, 47.8 +/- 27.4 pack-years; p0.0001). Men had a greater LAA% (24% +/- 12% vs 20% +/- 11%, respectively; p0.0001) and larger emphysematous spaces than women, and these differences persisted after adjusting for covariates (weight, pack-years of smoking, current smoking status, center of enrollment, and FEV(1) percent predicted; p = 0.0006). Women had a smaller SQRTWA and WA% after adjusting for covariates (p0.0001).Male smokers have more emphysema than female smokers, but female smokers do not show increased wall thickness compared with men.

SummaryBackgroundThe prevalence of depression in stable COPD patients varies markedly, possibly because of use of different scales. We aimed to assess depression using 2 different depression scales and to examine the association between depression and poor exercise performance, BODE index and muscle wasting in clinically stable COPD patients.Methods122 stable COPD patients were assessed with the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Brief Assessment Schedule Depression Cards (BASDEC). We also assessed patients with spirometry, bioelectrical impedance analysis, 6-minute walk distance (6MWD), St George's Respiratory Questionnaire (SGRQ) and MRC dyspnoea and Borg scales.ResultsThe CES-D and BASDEC scales detected almost similar prevalence rates of depression (21% vs 17%) with a Kappa coefficient of 0.68, p

Summary Background Impulse oscillometry system (IOS) assesses pulmonary resistance and reactance. We set out to investigate which IOS measurements are related to airflow obstruction, airway conductance and lung volumes in chronic obstructive pulmonary disease (COPD). Methods Ninety-four COPD patients were recruited and 58 agreed to follow up after 1 year. IOS measurements (R5, R20, X5 & Fres), body plethysmography (sGaw, FRC, TLC, RV & IC) and spirometry (FEV 1 ) were performed. Pearson or Spearman correlation determined the relationships between IOS and other measurements. Results R5, X5 and Fres were all significantly associated ( p 1 , sGaw, TLC, RV and IC. However, R20 was not related to any of these measurements except for RV. The strongest associations were observed between FEV 1 and the reactance measurements X5 ( r =0.48) and Fres ( r =−0.44), and sGaw with X5 ( r =0.47) and Fres ( r =0.51). The r values for the associations with TLC and IC were all There was no statistically significant change in the FEV 1 , R5, X5 or Fres after 1 year, but R20 significantly increased over the year. The changes in R5 and R20 did not significantly correlate with the changes in FEV 1 . In contrast, X5 changes were significantly related to FEV 1 changes over 1 year ( r =−0.27, p =0.05), while for Fres changes there was a trend to statistical significance ( p =0.08). Conclusions IOS reactance measurements are more closely related than resistance measurements to other pulmonary function measurements in COPD patients. The IOS reactance measurements appear to be indicative of changes in pulmonary compliance caused by airflow obstruction.

COPD is one of the most common causes of morbidity and mortality. Perhaps paradoxically, COPD also should be an orphan disease. Importantly, this could advance the development of treatments for COPD. There are two criteria for orphan status in the United States. Most widely known is the criterion of < 200,000 affected individuals; however, secondarily, is the impossibility for development costs to be recovered during the patent life of a product. COPD should qualify for the first criterion if the various conditions that comprise COPD are regarded separately. The subphenotyping of COPD into separate groups based on mechanism sets the stage for the rational development of therapeutics. In addition, many candidate treatments may alter the natural history of COPD. Testing them, however, will require large studies for a duration that will compromise the commercial life of any resulting product. Orphan status, therefore, could facilitate the development of treatments for both phenotypic subsets of COPD patients as well as aid the development of agents to alter the natural history of the disease. Post-drug approval regulations could require that agents approved under the orphan provisions are prospectively monitored, assuring that rigorous longitudinal data are generated. This approach could encourage the pharmaceutical industry to stratify studies based on a more detailed characterization of study subjects at baseline, thus approaching "many small COPDs" instead of a single large and heterogeneous COPD. This strategy may help to address the increasing burden that COPD presents and for which no novel clinical class of treatment has been introduced for 30 years.

BACKGROUND: Smoking is associated with an accelerated loss of lung function and inhalation accelerates the decline further. Exhaled CO reflects the exposure of smoke to the lungs. AIM: To investigate whether self-reported inhalation and type of cigarette influenced the level of exhaled CO and whether CO could provide additional information to usual measures of smoking regarding prediction of present lung function and decline in lung function over an extended period of time. METHOD: Cigarette smokers from the Copenhagen City Heart Study with valid measures of lung function and exhaled CO; in total 3738 subjects, 2096 women and 1642 men. RESULTS: Subjects not inhaling had slightly lower exhaled CO values than those inhaling, but substantially higher values than non-smokers (P

Background. In a population-based sample of smokers in early motivational stages, we found a high acceptance of smoking cessation groups. Methods. Inter99 is a randomized population-based intervention study, in Copenhagen, Denmark. Smokers in all motivational stages were included. All participants underwent a lifestyle consultation and 2,168 smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups. Results. Thirty-five percent were validated to be continuously abstinent at the end of the smoking cessation groups. Eighty-four percent of the smokers achieving sustained abstinence in our study had no serious plans to quit soon before the lifestyle consultation. Motivation to quit before the lifestyle consultation could not predict abstinence. Being a man, and having a job and at least 1 year of vocational training were predictors of abstinence in a multivariate model, whereas high nicotine dependence and living with a smoking spouse were predictors of failure. Conclusion. High cessation rates were obtained in a population of heavy smokers with moderate nicotine dependence. It was possible to obtain sustained abstinence in smokers in early motivational stages. These smokers would probably not have been reached by traditional smoking campaigns.

Whether women receive the same medical care for COPD as men and if they are at risk of different outcomes as a result, is not known. The Confronting COPD International Survey was performed in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK in 2000 with 3265 COPD participants. Forty-one per cent were women; mean age in women and men was 61.2 (SD 10.5) and 64.4 (11.0) years, mean pack-years of smoking 36 (29) and 46 (35) years, respectively. After adjusting for age, pack-years, country and severe dyspnea (MRC scores 5 and 4), women were less Likely to have had spirometry (OR 0.84, 95% C.I. 0.72-0.98) but more likely to get smoking cessation advice (OR 1.57, 1.33-1.86). Despite significantly lower pack-years of smoking, women were more likely to report severe dyspnea than men (OR 1.30, 1.10-1.54), with similar cough (OR 1.08, 0.92-1.27) and less sputum (OR 0.84, 0.72 0.98). There were no differences in the risk of hospitalisation or emergency room visit. This study indicates that gender differences in COPD care and outcomes exist. (C) 2004 Elsevier Ltd. All rights reserved.

Background: Depression increases disability and health care utilization in older patients with chronic obstructive pulmonary disease (COPD).Objectives: To determine contribution of depressive symptoms to the incidence of moderate-severe and severe acute exacerbations of COPD (AECOPD) over 3 years.Design: We analyzed data collected from a prospective cohort of patients with COPD (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; ECLIPSE).Setting: Multicentered outpatient.Participants: A total of 2059 patients with COPD with complete data (63.7% men, mean age 63.4 + 7.1 years).Measurements: Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Moderate-severe AECOPDs were collected; a subset of very severe AECOPD was defined as requiring hospital admission.Results: A total of 540 (26%) patients with COPD reported high depressive symptoms (CES-D >= 16). High depressive symptoms at baseline related to an increased risk of moderate-severe and severe AECOPD during the follow-up (odds ratio [OR] 1.18; 95% confidence interval [CI] 1.07-1.30; for moderate-severe and OR 1.36; 95% CI 1.09-1.69 for severe events risk of hospitalizations) independent of key covariates of an AECOPD history before recruitment in the study, history of gastroesophageal reflux, baseline severity of airflow limitation, and white blood cell count that were also associated with an increased risk of moderate to severe exacerbations (all P Conclusion: Presence of high depressive symptoms at baseline were associated with subsequent moderate-severe exacerbations and hospital admissions in patients with COPD over 3 years, independent of a history of exacerbations and other demographic and clinical factors. Targeted personalized medicinethat focuses both on AECOPD risk and depression may be a step forward to improving prognosis of patients with COPD. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Introduction Les patients atteints de BPCO sont a risque accru de pneumonie. Des etudes precedentes ont montre que le risque de pneumonie dans la BPCO est en partie lie au degre de severite de l’obstruction des voies aeriennes. De maniere importante, pour les patients recevant des traitements avec CSI, le risque est augmente chez ceux ayant une obstruction des voies aeriennes severe (30 % ≤ VEMS

Introduction Dans l’etude TORCH, l’association d’un β2 agoniste de longue duree d’action (LABA) (salmeterol) et d’un corticosteroide inhale (CSI) (propionate de fluticasone) n’a pas reduit significativement la mortalite, mais a ete associee dans une analyse post-hoc a une reduction du taux de declin du VEMS et a moins d’evenements cardiovasculaires (CV) chez des patients BPCO. L’analyse factorielle post-hoc a suggere que ces benefices etaient dus au salmeterol. Ici, nous reexaminons l’effet de ces composants dans une analyse factorielle predefinie de l’etude Summit (study to understand mortality and morbidity) dans laquelle le LABA etait le vilanterol (VI) et le CSI etaient le furoate de fluticasone (FF) ( Fig. 1 ). Methodes Summit etait une etude multicentrique randomisee controlee menee chez 16 485 patients (40–80 ans) atteints d’une BPCO moderee et d’un risque CV eleve qui ont recu un des quatre traitements inhales en une prise par jour : placebo (n = 4 111), CSI (FF ; n = 4 135), LABA (VI ; n = 4 118) et la therapie associee (FF/VI ; n = 4121). Le critere principal etait la mortalite toute cause confondue, le changement du taux de declin du VEMS et le critere CV compose etaient des criteres secondaires cles. Une analyse factorielle a ete realisee avec les facteurs FF et VI et leur interaction a egalement ete testee. Resultats Les participants etaient principalement des hommes (75 %) d’âge moyen (65 ± 8 ans) avec 47 % de fumeurs actifs et une moyenne de VEMS de 60 % de la valeur predite (54–65 %). Il n’y avait pas d’interaction statistiquement significative entre FF et VI sur les criteres principal ou secondaires (p ≥ = 0,693). La mortalite toute cause confondue n’a pas ete affectee par FF ou VI. Le taux de declin du VEMS a ete reduit de 9 mL/an avec FF, soit seul, soit en association avec VI. En revanche, VI n’a pas d’effet sur le taux de declin du VEMS. La probabilite d’un evenement CV compose etait inchangee selon le traitement. Conclusion Chez les patients BPCO avec une obstruction moderee des voies aeriennes et une maladie CV le traitement avec VI seul ou en association n’a pas d’effet sur le risque de deces ou sur le taux de declin de la fonction pulmonaire. L’utilisation de FF n’a pas d’impact sur le risque de deces, mais etait associee a une reduction du declin du VEMS. L’analyse factorielle a montre que les effets de FF ou VI etaient coherents, independamment du fait qu’ils aient ete utilises seuls ou en association. Financements Finance par GSK 113782 ( NCT01313676 ).

Background. The aim of this study was to examine the extent and gender distribution of unassisted tobacco reduction and cessation in a cohort of moderate and heavy smokers and to identify possible predictor variables associated with these changes in smoking behavior. Methods. This was a prospective population study of 3,791 moderate and heavy smokers, 15 g tobacco/day or more, who were enrolled in the Copenhagen City Heart Study in 1976–1978 and attended a reexamination 5 years later. Data on smoking behavior were collected at baseline and follow-up. Smoking reduction was defined as a decrease in mean daily tobacco consumption of 10 g or more. Using multivariate logistic regression, subjects who reported reduced smoking or who reported smoking cessation were compared with subjects who continued the habit unchanged. Results. After 5 years 13% of the men and 9% of the women had reduced their tobacco consumption, and 9 and 7%, respectively, had quit altogether. Smoking reduction was strongly associated with high tobacco consumption (25+ g/day) at baseline and also with severely impaired lung function (FEV 1 25). Predictors of smoking cessation included impaired lung function and a tobacco consumption of 15–24 g/day. Additional determinants of smoking reduction and cessation such as inhalation habits and sociodemographic variables differed by gender. Conclusions. Several predictors of smoking reduction and cessation were identified, indicating that these subgroups of smokers differ substantially from continuing smokers. This should be taken into account when assessing potential health benefits from these changes in smoking behavior.

Pneumocystis carinii pneumonia is the most common and serious of the pulmonary complications of AIDS. Despite this, many basic aspects in the pathogenesis of HIV-associated P carinii pneumonia are unknown. We therefore undertook a light and electron microscopic study of transbronchial biopsy specimens to compare pathologic features of P carinii pneumonia and other HIV-related lung diseases.Thirty-seven consecutive HIV-infected patients undergoing a diagnostic bronchoscopy.P carinii pneumonia was characterized by an increase in inflammation, edema, exudate, fibrosts, type II pneumocyte proliferation, and cellular infiltration of the alveolar wall when compared with other lung diseases (all p0.05). Electron microscopy showed apposition of the trophozoite to the type I pneumocyte. Erosion of type I pneumocytes was observed in 13 of 15 patients with P carinii pneumonia, whereas none without P carinii pneumonia had this finding (p0.05). Erosion of the type II pneumocyte was not observed.Inflammation, interstitial fibrosis, and alveolar epithelial erosion are characteristic features of P carinii pneumonia. The changes may form the pathologic basis for the respiratory failure seen in patients with P carinii pneumonia. Electron microscopy did not show any diagnostie advantage over conventional light microscopy using routine stains.

Objective To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). Design Analysis of clinical data during a 5-year period. Setting Department of infectious diseases where clinical and paraclinical data on patients suspected of having PCP have been sampled prospectively. Patients 148 consecutive patients with a first episode of PCP in a 5-year period. Main outcome measure Vital status 3 months after diagnosis of PCP. Results Patients with PCP treated with adjunctive CS who had CMV cultured from BAL fluid had a two times higher mortality within 3 months from bronchoscopy than others (p=0.08). This difference could not be explained by differences in CD4 count, Po 2 or PCO 2 at time of bronchoscopy. Conclusion With the accepted usage of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS. (CHEST 1995; 108:411-14)