Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial.

Background: Despite inhaled corticosteroid plus long-acting β-agonist (ICS/LABA) therapy, 30-50% of patients with moderate or severe asthma remain inadequately controlled. We investigated the safety and efficacy of single-inhaler fluticasone furoate plus umeclidinium plus vilanterol (FF/UMEC/VI) compared with FF/VI.

Methods: In this double-blind, randomised, parallel-group, phase 3A study (Clinical Study in Asthma Patients Receiving Triple Therapy in a Single Inhaler [CAPTAIN]), participants were recruited from 416 hospitals and primary care centres across 15 countries.

Single-Inhaler Triple Therapy and Health-Related Quality of Life in COPD: The IMPACT Study.

Introduction: The phase 3 InforMing the PAthway of COPD (chronic obstructive pulmonary disease) Treatment (IMPACT) trial, single-inhaler therapy with fluticasone furoate (FF) 100 μg, umeclidinium (UMEC) 62.5 μg, and vilanterol (VI) 25 μg demonstrated a reduction in the rate of moderate or severe exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This article reports additional evidence of improvements in symptoms and health-related quality of life (HRQoL) with FF/UMEC/VI compared with either FF/VI or UMEC/VI from the IMPACT study.

A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids.

Background: Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.

Methods: This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information. Report ACM and impact of stepping down therapy, following collection of additional vital status data.

Anaemia and iron dysregulation: untapped therapeutic targets in chronic lung disease?

Hypoxia is common in many chronic lung diseases. Beyond pulmonary considerations, delivery of oxygen (O) to the tissues and subsequent O utilisation is also determined by other factors including red blood cell mass and iron status; consequently, disruption to these mechanisms provides further physiological strains on an already stressed system. O availability influences ventilation, regulates pulmonary blood flow and impacts gene expression throughout the body.

Circulating neutrophils levels are a predictor of pneumonia risk in chronic obstructive pulmonary disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; however, no definitive biomarkers of risk have been established. We hypothesized that blood neutrophils would help predict pneumonia risk in COPD.

Methods: A meta-analysis of randomized, double-blind clinical trials of COPD patients meeting the following criteria were selected from the GlaxoSmithKline trial registry: ≥1 inhaled corticosteroid-containing (ICS) arm (fluticasone propionate/salmeterol or fluticasone furoate/vilanterol), a control arm (non-ICS), pre-randomization blood neutrophil counts, ≥24-week duration.

Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.

Background: Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS.

Reliability, validity and responsiveness of E-RS:COPD in patients with spirometric asthma-COPD overlap.

Background: The Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS:COPD) is a patient-reported diary that assesses respiratory symptoms in stable COPD.

Methods: This post hoc analysis of a randomized, double-blind, parallel-arm trial (GSK ID: 200699; NCT02164539) assessed the structure, reliability, validity and responsiveness of the E-RS, and a separate wheeze item, for use in patients with a primary diagnosis of asthma or COPD, but with spirometric characteristics of both (fixed airflow obstruction and reversibility to salbutamol; a subset of patients referred to as spirometric asthma-COPD overlap [ACO]; N = 338).

Results: Factor analysis demonstrated that E-RS included Cough and Sputum, Chest Symptoms, and Breathlessness domains, with a Total score suitable for quantifying overall respiratory symptoms (comparative fit index: 0.

Seasonal variation in asthma exacerbations in the AUSTRI and VESTRI studies.

http://ow.ly/pcZF30o8hHk.

Blood eosinophils: a biomarker of COPD exacerbation reduction with inhaled corticosteroids.

Background: Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS). We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.

Methods: The studies assessed ICS/long-acting β agonist (LABA) combinations vs LABA alone.

Blood eosinophil levels as a biomarker in COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder and patients respond differently to treatment. Blood eosinophils are a potential biomarker to stratify patient subsets for COPD therapy. We reviewed the value of blood eosinophils in predicting exacerbation risk and response to corticosteroid treatment in the available literature (PubMed articles in English; keywords: "COPD" and "eosinophil"; published prior to May 2017).

Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD.

Background: The benefits of triple therapy for chronic obstructive pulmonary disease (COPD) with an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β-agonist (LABA), as compared with dual therapy (either inhaled glucocorticoid-LABA or LAMA-LABA), are uncertain.

Methods: In this randomized trial involving 10,355 patients with COPD, we compared 52 weeks of a once-daily combination of fluticasone furoate (an inhaled glucocorticoid) at a dose of 100 μg, umeclidinium (a LAMA) at a dose of 62.5 μg, and vilanterol (a LABA) at a dose of 25 μg (triple therapy) with fluticasone furoate-vilanterol (at doses of 100 μg and 25 μg, respectively) and umeclidinium-vilanterol (at doses of 62.

Use of clinical characteristics to predict spirometric classification of obstructive lung disease.

Background: There is no consensus on how to define patients with symptoms of asthma and chronic obstructive pulmonary disease (COPD). A diagnosis of asthma-COPD overlap (ACO) syndrome has been proposed, but its value is debated. This study (GSK Study 201703 [NCT02302417]) investigated the ability of statistical modeling approaches to define distinct disease groups in patients with obstructive lung disease (OLD) using medical history and spirometric data.

Biological effects of p38 MAPK inhibitor losmapimod does not translate to clinical benefits in COPD.

Rationale: p38 mitogen-activated protein kinase (MAPK) expression is increased in chronic inflammatory disease. Losmapimod, a p38 MAPK inhibitor, has been developed as a potential anti-inflammatory therapy in COPD.

Objectives: To evaluate the effect of losmapimod in reducing exacerbations in subjects with moderate-to-severe COPD.

The effect of umeclidinium on lung function and symptoms in patients with fixed airflow obstruction and reversibility to salbutamol: A randomised, 3-phase study.

Introduction: The long-acting muscarinic antagonist, umeclidinium (UMEC), combined with the inhaled corticosteroid, fluticasone furoate (FF), improves lung function in symptomatic patients with asthma. We assessed FF/UMEC in patients with a primary diagnosis of asthma or chronic obstructive pulmonary disease (COPD), but physiological characteristics of both (fixed airflow obstruction and reversibility to salbutamol).

Methods: This double-blind, parallel-arm, 3-phase study randomised 338 patients (1:1:1:1:2:2) to FF 100 mcg alone or combined with UMEC (15.

FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited.

Objectives: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.

Methods: The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.

Understanding and measuring symptoms and health status in asthma COPD overlap: content validity of the EXACT and SGRQ.

Background: Asthma-chronic obstructive pulmonary disease overlap (ACO) differs from asthma and chronic obstructive pulmonary disease (COPD) in demographics, phenotypic characteristics and outcomes, yet the patient experience of ACO is poorly characterized. We aimed to understand and compare the patient experience of symptoms and domains of impact in ACO relative to COPD, and assess the content validity of existing patient-reported outcome (PRO) instruments in ACO.

Methods: This US qualitative, interview study included patients who met American Thoracic Society/European Respiratory Society spirometric criteria for COPD.