Baseline FeNO Independently Predicts the Dupilumab Response in Patients With Moderate-to-Severe Asthma.

Background: FeNO may have a role as both a prognostic and predictive biomarker in combination with eosinophils for assessing responsiveness to some biological therapies.

Objective: We evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled moderate-to-severe asthma.

Methods: We performed a post hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged 12 years and older with uncontrolled moderate-to-severe asthma, who received dupilumab 200 or 300 mg, or placebo every 2 weeks up to 52 weeks.

Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.

Background: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).

Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.

Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg).

Assessing factors influencing smoking and smoking cessation within Chinese communities in the Greater Vancouver Area: A qualitative exploratory study.

Introduction: The prevalence of smoking is high within Chinese-Canadian communities and there is a lack of culturally and linguistically appropriate smoking cessation resources and services. We aimed to ascertain factors affecting smoking and smoking cessation from the perspectives of current smokers and key informants.

Methods: As part of a multistage mixed-methods study taking place from January 2013 to June 2014, a qualitative exploratory study design was conducted applying a community-based participatory research approach.

Asthma exacerbations and worsenings in patients aged 1-75 years with add-on tiotropium treatment.

This review explores the effect of tiotropium Respimat® add-on therapy on asthma exacerbations and worsenings, adverse events (AEs) related to exacerbations and symptoms and any effects on seasonality across the 10 UniTinA-asthma® clinical trials comprising over 6000 patients. When added on to inhaled corticosteroids ± additional therapies, tiotropium significantly reduced the risk of exacerbations and worsenings in adults with symptomatic severe asthma and provided a non-significant improvement in worsenings in adults with symptomatic moderate and mild asthma, which was significant for patients with moderate asthma receiving tiotropium 2.5 µg once daily vs.

Non-steroidal Anti-inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review.

There have been concerns regarding the safety of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with respiratory infections. However, to date, the quality of the evidence has not been systematically assessed. The purpose of this systematic review was to evaluate the role of NSAIDs on pneumonia complications.

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis.

Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT).

Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis.

Study Design And Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada.

The evolving algorithm of biological selection in severe asthma.

New therapeutic options for severe asthma have recently emerged, mostly in the form of monoclonal antibodies ("biologicals") targeting relevant inflammatory pathways. Currently available agents target different aspects of "Type 2" immunity, and their indications often include overlapping patient groups. We present a round-table discussion that took place during the Annual Meeting of the Respiratory Effectiveness Group (REG), on the reasoning behind the use of different add-on medications for severe asthma, and crucially, on selection strategies.

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5.

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4-5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2-5, a post hoc analysis of five double-blind trials (12-48-weeks; patients aged 18-75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.

Two-year integrated steroid-sparing analysis and safety of benralizumab for severe asthma.

Objective: Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year and decreases oral corticosteroid (OCS) use after 28 weeks for patients with severe, uncontrolled eosinophilic asthma. We assessed whether these effects on OCS reduction are sustained for up to an additional year of treatment while maintaining an acceptable safety profile.

Methods: Data on OCS maintenance dosage were collected for adult patients with baseline blood eosinophil counts ≥150 cells/μL treated with add-on benralizumab 30 mg (every 4 [Q4W] or 8 weeks [Q8W; first three doses Q4W]) from the 28-week ZONDA study and were integrated with results from the predefined 56-week adult completion phase of the BORA extension study.

Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma.

Background: Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody. Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year for patients with severe, uncontrolled eosinophilic asthma.

Objective: We explored whether benralizumab efficacy was sustained after an additional year of treatment while maintaining an acceptable safety profile.

Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV.

Background: The primary lung function endpoint in clinical trials in adolescent and adult patients with asthma is usually forced expiratory volume in one second (FEV). The objective of our analysis was to assess whether peak expiratory flow (PEF) is a suitable alternative primary lung function endpoint.

Methods: For this assessment, we calculated post hoc the correlation between pre-dose FEV and pre-dose PEF measured under supervision in the clinic and, for both lung function parameters, the correlations between supervised clinic and unsupervised home measurements, using the results from the 8 Phase III parallel-group trials of the global clinical development programme with tiotropium Respimat® in patients with asthma aged 12 to 75 years.

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial.

Background: Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma.

Methods: We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries.

Tiotropium add-on to inhaled corticosteroids versus addition of long-acting β-agonists for adults with asthma.

Additional management options, and better use of current options, are needed to help support a large proportion of patients with asthma whose symptoms remain uncontrolled on inhaled corticosteroids (ICS). Here, we aim to review the safety and efficacy of adding tiotropium to ICS compared with adding a long-acting β-agonist (LABA) for adults whose asthma is not well controlled on ICS alone. Adding tiotropium to a background of ICS provides beneficial effects that are comparable with addition of a LABA in terms of lung function measures, exacerbations, asthma control and other endpoints.

Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma.

Benralizumab is an anti-eosinophilic monoclonal antibody that reduces exacerbations and improves lung function for patients with severe, uncontrolled asthma with eosinophilic inflammation. We evaluated the impact of baseline factors on benralizumab efficacy for patients with severe asthma.This analysis used pooled data from the SIROCCO (ClinicalTrials.

Inhaled Steroids and Active Smoking Drive Chronic Obstructive Pulmonary Disease Symptoms and Biomarkers to a Greater Degree Than Airflow Limitation.

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and development of novel therapeutics requires an understanding of pathophysiologic phenotypes.

Objectives: The purpose of the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study was to correlate clinical features and biomarkers with molecular characteristics in a well-profiled COPD cohort.

Methods: A total of 67 COPD subjects (forced expiratory volume in the first second of expiration [FEV]: 45%-80% predicted) and 63 healthy smoking and nonsmoking controls underwent multiple assessments including patient questionnaires, lung function, and clinical biomarkers including fractional exhaled nitric oxide (FENO), induced sputum, and blood.

Testing the External Validity of a Discrete Choice Experiment Method: An Application to Latent Tuberculosis Infection Treatment.

Objectives: To explore the external validity and predictive power of stated preferences obtained from a discrete choice experiment (DCE) by comparing the predicted behavior of respondents to their actual choices at an individual level.

Methods: A DCE was performed in patients before being offered treatment for latent tuberculosis infection. A mixed logit model was estimated using hierarchical Bayes.

Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial.

Background: Eosinophilia is associated with worsening asthma severity and decreased lung function, with increased exacerbation frequency. We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia.

Methods: We did a randomised, double-blind, parallel-group, placebo-controlled phase 3 study at 374 sites in 17 countries.