Les essais contrôlés randomisés (ECR) comparant les trithérapies corticostéroïde inhalé/agoniste β2 de longue durée d’action/antagoniste muscarinique de longue durée d’action (CSI/LABA/LAMA) sont limités. Cette méta-analyse en réseau (NMA, Network Meta-Analysis) étudie l’efficacité relative du furoate de fluticasone/uméclidinium/vilantérol (FF/UMEC/VI) (100/62,5/25 μg) par rapport aux autres trithérapies chez les patients atteints de bronchopneumopathie chronique obstructive (BPCO). Une NMA (méthode fréquentiste, modèles à effets fixes et aléatoires) a été réalisée après revue systématique de la littérature (RSL). La RSL a identifié les ECR chez les patients BPCO ≥ 40 ans, qui comparent l’association CSI/LABA/LAMA à tout autre schéma thérapeutique. Les différences entre les taux d’incidence annualisés des exacerbations modérées et sévères ont été déterminées. Toutes les études (n = 17) rapportant les exacerbations comme critère d’évaluation ont été incluses dans la NMA. Une analyse en sous-groupe incluant des études avec au moins 24 semaines de suivi (n = 10 identifiées, mais 5 sont déconnectées du réseau) a été réalisée pour tenir compte de l’hétérogénéité induite par les différences de durée de suivi. Des analyses de sensibilité ont évalué la robustesse des résultats. L’association FF/UMEC/VI a montré des améliorations statistiquement significatives des taux annualisés des exacerbations modérées/sévères vs l’association budésonide/bromure de glycopyrronium/fumarate de formotérol (BUD/GLY/FOR) 160/18/9,6 et BUD/GLY/FOR 320/18/9,6, ainsi que des estimations ponctuelles moyennes favorables des taux d’incidence (classement des traitements selon la valeur du p-score (approche statistique)) par rapport à toutes les autres trithérapies, à l’exception de l’association TIO18 + BUD/FOR 320/9 (non statistiquement significative) (Fig. 1). Une hétérogénéité substantielle a été observée concernant la définition des exacerbations modérées et sévères et la durée du suivi. Cette NMA suggère une efficacité favorable à long terme de la trithérapie FF/UMEC/VI à inhalateur unique ELLIPTA, montrant une amélioration des taux annuels combinés d’exacerbations modérées et sévères par rapport à la plupart d’autres thérapies couramment utilisées. D’autres analyses seront nécessaires à l’avenir, au fur et à mesure que des preuves supplémentaires seront disponibles.

Einleitung Die Anzahl randomisierter, kontrollierter Studien, die Triple-Therapien aus inhalativem Kortikosteroid, langwirksamem β2-Agonisten und langwirksamem Muskarinantagonisten (ICS/LABA/LAMA) vergleichen, sind limitiert. Diese NMA untersuchte die Wirksamkeit von FF/UMEC/VI (100/62,5/25 μg) gegenüber alternativen Therapien bei Patienten mit COPD.

Real world data comprise information on health care that is derived from multiple sources outside typical clinical research settings. This review focuses on what real world evidence tells us about problems with the diagnosis of chronic obstructive pulmonary disease (COPD), problems with the initial and follow-up pharmacological and non-pharmacological management, problems with the management of exacerbations and problems with palliative care. Data from real world studies show errors in the management of COPD with delays to diagnosis, lack of confirmation of the diagnosis with spirometry, lack of holistic assessment, lack of attention to smoking cessation, variable adherence to management guidelines, delayed implementation of appropriate interventions, under-recognition of patients at higher risk of adverse outcomes, high hospitalisation rates for exacerbations and poor implementation of palliative care. Understanding that these problems exist and considering how and why they occur is fundamental to developing solutions to improve the diagnosis and management of patients with COPD.

Patients with COPD present in different ways at different stages of the disease. The commonest symptoms are breathlessness and cough but there are often also systemic symptoms such as leg ache and fatigue. COPD symptoms lead to significant limitations in activities and affect patient's ability to work. Quantification of the severity and impact of COPD symptoms allows a better understanding of the patients' status and is fundamental to the choice of initial and maintenance therapy. Many patients with COPD also have comorbidities which contribute to the burden of living with COPD. Making a diagnosis of COPD depends on demonstrating the presence of fixed airflow obstruction in a person who has symptoms suggestive of COPD and exposure to a risk factor in the absence of alternative causes.

Background The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk. Methods and Results This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time‐dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time‐to‐first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations. CVAESI risk was compared between the period before and during/after exacerbation. CVAESI risk increased significantly during a moderate (hazard ratio [HR], 2.63 [95% CI, 2.08–3.32]) or severe (HR, 21.84 [95% CI, 17.71–26.93]) exacerbation and remained elevated for 30 days following an exacerbation (moderate: HR, 1.63 [95% CI, 1.28–2.08]; severe: HR, 1.75 [95% CI, 0.99–3.11; nonsignificant]) and decreased over time, returning to baseline by 90 days. Risk of CVAESI resulting in hospitalization or death also increased during an exacerbation (moderate: HR, 2.46 [95% CI, 1.53–3.97]; severe: HR, 41.29 [95% CI, 30.43–56.03]) and decreased in a similar time‐dependent pattern. Results were consistent regardless of exacerbation history, cardiovascular risk at screening, or study treatment. Conclusions Overall risk of cardiovascular events was higher during and in the 30 days following chronic obstructive pulmonary disease exacerbations, even among those with low cardiovascular risk, highlighting the need for exacerbation prevention and vigilance for cardiovascular events following exacerbations. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02164513; Unique identifier: NCT02164513

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" patients with COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

PURPOSE: 5-10% of patients (pts) with asthma experience severe disease.Of these, an estimated 30-45% require oral corticosteroids (OCS) to manage their asthma.Dupilumab, a fully human mAb, blocks the shared receptor component for IL-4/ IL-13, key and central drivers of type 2 inflammation in multiple diseases.In phase 3 VENTURE (NCT02528214), add-on dupilumab 300 mg every 2 weeks (q2w) vs placebo reduced OCS (prednisone/prednisolone) maintenance dose and severe asthma exacerbation rate and improved pre-bronchodilator (BD) FEV 1 independent of baseline eosinophils in pts aged $12 years with OCS-dependent severe asthma; dupilumab was well tolerated.This post hoc analysis evaluated the efficacy of dupilumab in reducing OCS use and improving clinical outcomes in pts grouped by baseline (BL) optimized OCS dose.

Background: IMPACT is a randomized, multicenter study (52 weeks) comparing the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs. FF/VI and UMEC/VI in patients ≥ 40 years of age with symptomatic COPD and a history of exacerbations (N = 10,355). For the primary endpoint, FF/UMEC/VI demonstrated a significant reduction in moderate (mod)/severe (sev) exacerbations vs. FF/VI and UMEC/VI (NEJM 2018; 378: 18).

Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future.

Background: To determine overall benefit-risk, we examined the effect of single inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI and FF/VI on the composite outcome of acute exacerbation of COPD or pneumonia in the IMPACT study, a 52-week, randomized, multicentre study in patients with symptomatic COPD and prior exacerbation. Methods: We defined two composite outcomes: time to first moderate (required antibiotics and/or systemic corticosteroids)/severe (required hospitalisation) exacerbation or pneumonia; and time to first severe exacerbation/hospitalised pneumonia. Analyses were based on a proportional hazards model. Results: Moderate/severe exacerbations occurred in 47% of patients randomized to FF/UMEC/VI, 49% in those randomized to FF/VI and 50% in those randomized to UMEC/VI. Pneumonias occurred in 8%, 7%, and 5% of patients in these groups. FF/UMEC/VI reduced the risk of first moderate/severe exacerbation or pneumonia vs. FF/VI by 13.2% (95%CI 7.8%-18.3%; p<0.001) and vs. UMEC/VI by 13.1% (95%CI 6.3%-19.3%; p<0.001) by time to first analysis. There was no difference in the risk of a moderate/severe exacerbation or pneumonia between FF/VI and UMEC/VI. FF/UMEC/VI reduced the risk of a severe exacerbation or hospitalized pneumonia vs. UMEC/VI by 16.9% (95%CI 4.2%-27.8%; p=0.011) by time to first analysis. There was no difference in the risk of a severe exacerbation or hospitalized pneumonia between FF/UMEC/VI and FF/VI or between FF/VI and UMEC/VI. Conclusion: These composite exacerbation/pneumonia outcomes support a favourable benefit-risk profile of FF/UMEC/VI compared with FF/VI and UMEC/VI in patients with moderate to severe COPD and prior exacerbation.

Lung function, health status, and exacerbations are important measures of chronic obstructive pulmonary disease (COPD) progression. So far, treatments in COPD have failed to demonstrate a reduction in rate of decline of trough forced expiratory volume in 1 second (FEV1) or mortality, which may be related to the multicomponent nature of COPD. This post hoc analysis assessed the suitability to predict long-term outcomes using a composite endpoint in patients with moderate to very severe COPD in the UPLIFT trial that may better reflect the multifactorial disease progression in COPD.

The BMJ reports on Gaza’s post-conflict health infrastructure.1 Since 30 March 2018, Palestinians civilians who have been living as refugees in Gaza since 1948 have been gathering in mass, unarmed demonstrations about their political predicament and the ongoing effects of the 12 year long Israeli siege. Since 2014 Israel has further tightened the passage of essential medicines and equipment into Gaza, where hospitals are depleted of …