Explore the vast range of titles available.

Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear. In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV ) at weeks 12 and 52 and in the St. George's Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52. A total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P = 0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab. In patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.).

In this trial, long-term supplemental oxygen treatment did not result in longer survival than no use of supplemental oxygen among patients with stable COPD and moderate resting desaturation (Spo2, 89 to 93%) or moderate exercise-induced desaturation. Two trials that were conducted in the 1970s showed that long-term treatment with supplemental oxygen reduced mortality among patients with chronic obstructive pulmonary disease (COPD) and severe resting hypoxemia. 1 , 2 These results led to the recommendation that supplemental oxygen be administered to patients with an oxyhemoglobin saturation, as measured by pulse oximetry (Spo 2 ), of less than 89%. 3 , 4 In the 1990s, two trials evaluated long-term treatment with supplemental oxygen in patients with COPD who had mild-to-moderate daytime hypoxemia; neither trial showed a mortality benefit, but both were underpowered to assess mortality. 5 , 6 The effects of oxygen treatment on . . .

RationalePulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).ObjectiveTo investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.MethodsIn this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline. The primary analysis was based on the intention-to-treat principle.Measurements and main resultsThe primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).ConclusionPTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.Trial registration numberClinicalTrials.gov (NCT02667171), 28 January 2016.

PurposeTo compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU).MethodsWe conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%.ResultsA total of 302 patients were randomized into the PCT (n = 151) and control (n = 151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI − 0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n = 119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p = 0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2 ± 6.5 days in the PCT group vs. 5.4 ± 4.4 days in the control group, p = 0.85 and 7.9 ± 8 days in the PCT group vs. 7.7 ± 5.7 days in the control group, p = 0.75, respectively).ConclusionThe PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.

Aotearoa New Zealand (NZ) homes are cold by international standards, with many failing to achieve temperatures recommended by WHO housing and health guidelines. Despite strong evidence of seasonal exacerbations in Chronic Obstructive Pulmonary Disease (COPD), there has been little examination of the effect of household warmth, or housing quality on COPD outcomes. The Warm Homes for Elder New Zealanders (WHEZ) study aimed to see if subsidising electricity costs would improve the health outcomes of older people with COPD. Previous analysis showed a modest, typically 2-10% dependent on prior usage, increase in electricity use among the subsidised households. Participants aged over 55 with doctor-diagnosed COPD were recruited from three regional centres, and where possible their dwelling was insulated after enrolment. A single-blinded randomised controlled trial of the effect of an electricity voucher (NZ$500) on health care usage during winter was carried out in three locations across New Zealand. The primary outcome was exacerbations treated with antibiotics, and/or corticosteroids. The Clinical Trial Registration is NCT01627418. Of the 520 participants assigned to a wave, partial or better data was achieved for 424; 215 of those were randomised to the early intervention group, and 209 to receive the intervention later. Despite the modest increase in energy use by study households, reported previously, there was no significant difference between study arms in the frequency of exacerbation of COPD (0.089, p=0.5875, 95% CI -1.406-1.584) nor hospitalisations. An exploratory analysis suggested a lower mortality among participants assigned to receive the intervention first (OR 0.310, p=0.0175, 95% CI 0.118-0.815). This study showed little effect of winter electricity vouchers on exacerbations of COPD. However, such vouchers increased energy use and may have reduced overall mortality. A larger study, particularly with susceptible subpopulations, is recommended to examine this mortality impact further.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk. Determine whether AECOPD events are associated with increased risk of subsequent CVD. We performed a secondary cohort analysis of the SUMMIT (Study to Understand Mortality and Morbidity) trial, a convenience sample of current/former smokers with moderate COPD from 1,368 centers in 43 countries. All had CVD or increased CVD risk. AECOPD was defined as an increase in respiratory symptoms requiring treatment with antibiotics, systemic corticosteroids, and/or hospitalization. CVD events were a composite outcome of cardiovascular death, myocardial infarction, stroke, unstable angina, and transient ischemic attack. All CVD events were adjudicated. Cox proportional hazards models compared the hazard for a CVD event before AECOPD versus after AECOPD. Among 16,485 participants in SUMMIT, 4,704 participants had at least one AECOPD and 688 had at least one CVD event. The hazard ratio (HR) for CVD events after AECOPD was increased, particularly in the first 30 days after AECOPD (HR, 3.8; 95% confidence interval, 2.7-5.5) and was elevated up to 1 year after AECOPD. The 30-day HR after hospitalized AECOPD was more than twofold greater (HR, 9.9; 95% confidence interval, 6.6-14.9). In patients with COPD with CVD or risk factors for CVD, exacerbations confer an increased risk of subsequent CVD events, especially in hospitalized patients and within the first 30 days after exacerbation. Patients and clinicians should have heightened vigilance for early CVD events after AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT 01313676).

Background The “can do, do do” concept aims at identifying subgroups among persons with chronic obstructive pulmonary disease (COPD). Following a two-dimensional categorization, individuals are binarily classified with respect to their levels of physical capacity (“can’t do” or “can do”) and physical activity (“don’t do” or “do do”), resulting in four disjunct quadrants. The approach has been debated recently and the latest articles have concluded that the quadrants should be specifically examined in terms of psychological aspects of physical activity. Therefore, the goal of the present study was to explore the role of psychological variables in physical activity in the context of the “can do, do do” quadrant concept. Methods Within the scope of secondary data analyses of the “Stay Active After Rehabilitation” (STAR) randomized controlled trial, a total of 298 COPD rehabilitants of an inpatient pulmonary rehabilitation program were grouped into the suggested quadrants. We set fixed cut-offs at 70% of relative 6-min walking test performances for healthy individuals (physical capacity dimension) and 5.000 steps per day (physical activity dimension). Univariate and multivariate logistic regression analyses served to analyze whether depression scores, fear avoidance behaviors, disease-specific anxiety, self-concordance for physical activity, and five indicators of physical activity-related health competence (PAHCO) effectively discriminated between the “don’t do” and “do do” groups. Results Among persons with lower relative physical capacity, depression scores, fear avoidance behaviors, and disease-specific anxiety (univariate case) significantly differentiated between the more and the less active. Among persons with higher relative physical capacity, fear avoidance behaviors, disease-specific anxiety, as well as three PAHCO indicators (physical activity-specific self-efficacy, self-control, and affect regulation) significantly separated the more and the less active. In multivariate analyses, only fear avoidance behaviors and affect regulation discriminated among individuals with better relative physical capacity. Conclusion The findings identified important psychological and competence-oriented variables that explain discrepancies in the quadrant concept. Based on this, we discuss implications for physical activity promotion in individuals with COPD. Respiratory research can benefit from future studies complementing the quadrant concept through further behavioral analyses. Trial registration Clinicaltrials.gov, ID: NCT02966561. Registered 17 November, 2016, https://clinicaltrials.gov/ct2/show/NCT02966561 .

Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD). In a phase 3, double-blind, randomized, placebo-controlled trial, patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy were assigned, in a 1:1 ratio, to receive mepolizumab (at a dose of 100 mg) or placebo subcutaneously every 4 weeks for 52 to 104 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Secondary end points, tested hierarchically to control for multiplicity, were moderate or severe exacerbation as assessed in a time-to-first-event analysis, measures of health-related quality of life and symptoms, and the annualized rate of exacerbations leading to an emergency department visit, hospitalization, or both. Of the 804 patients who underwent randomization, 403 were assigned to receive mepolizumab and 401 to receive placebo. The annualized rate of moderate or severe exacerbations was significantly lower with mepolizumab than with placebo (0.80 vs. 1.01 events per year; rate ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.01). The time to the first moderate or severe exacerbation was longer with mepolizumab than with placebo (Kaplan-Meier median time to the first moderate or severe exacerbation, 419 vs. 321 days; hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = 0.009). Between-group differences in measures of health-related quality of life and symptoms were not significant; thus, no statistical inferences regarding subsequent secondary end points in the statistical testing hierarchy were made. The incidence of adverse events was similar in the mepolizumab and placebo groups. Treatment with mepolizumab led to a lower annualized rate of moderate or severe exacerbations when added to background triple inhaled therapy among patients with COPD and an eosinophilic phenotype. (Funded by GSK; MATINEE ClinicalTrials.gov number, NCT04133909.).

Background Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE). Methods We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography. Results COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage. The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study. The distribution of these variables within each GOLD stage was wide. Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation. The amount of emphysema increased with GOLD severity. The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage. Some gender differences were also identified. Conclusions The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

BackgroundPulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor. We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.MethodsA randomised controlled equivalence trial with 12 months follow-up. Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist. The primary outcome was change in 6 min walk distance (6MWD).ResultsWe enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80). Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7). At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9). Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1). The per-protocol analysis showed the same pattern of findings. Neither group maintained postrehabilitation gains at 12 months.ConclusionsThis home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation. Neither model was effective in maintaining gains at 12 months. Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.Trial registration numberNCT01423227, clinicaltrials.gov.