AZD0449, an inhaled JAK1 inhibitor, in healthy participants and patients with mild asthma.

Aims: Inhaled corticosteroids (ICS) plus bronchodilator are recommended for the treatment of asthma. Targeting the JAK1-dependent pathway may be an alternative for asthma management in patients with incomplete response to ICS. The aim of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD0449, a novel JAK1 selective inhibitor, following inhaled (dry powder, nebulized) and intravenous administration to healthy participants and patients with mild asthma.

Low Lung Function in Middle-Aged Smokers Impacts Health Status, Morbidities, and Mortality: An Observational Analysis of the Lovelace Smokers Cohort.

Background: Pulmonary function tests may predict future outcomes; however, they are not often performed in middle aged individuals at risk for future airway obstruction. We examined whether smokers with low lung function have increased risk of developing health problems and mortality over time.

Methods: Current and ever smokers (n=830) from the Lovelace Cohort aged 40-60 years without baseline airway obstruction and with at least two spirometry measurements over 18 months were included.

A Randomized, Double-Blind Crossover Study of Change in Post-Dose Lung Function with Hydrofluoroolefin-1234ze, a Next-Generation Propellant for Metered Dose Inhalers, in Participants with Asthma.

Pressurized metered dose inhalers (pMDIs) currently contain propellants with relatively high global warming potential (GWP), such as hydrofluoroalkane-134a (HFA-134a). Hyrofluoroolefin-1234ze (HFO-1234ze) is a near-zero GWP propellant in development for use in future pMDIs. This Phase IIIb, multicenter, randomized, double-blind, single-dose crossover study aimed to assess post-dose lung function and clinical manifestations of bronchospasm following single doses of HFA-134a and HFO-1234ze via pMDI (four inhalations with no active drugs) in participants with well or partially controlled asthma.

Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab.

Background: CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma.

Methods: This analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo.

Impact of season and geography on CompEx Asthma: a composite end-point for exacerbations.

Background: CompEx Asthma, a novel composite end-point combining severe exacerbations (SevEx) with asthma-worsening events, was recently developed. Further characterisation of CompEx Asthma is needed to illustrate the applicability of this end-point. The objective was to evaluate CompEx Asthma as a rate end-point to determine how seasonal and geographical factors impact this novel outcome.

Serious Asthma Outcomes and Asthma Exacerbations with Maintenance on Inhaled Corticosteroid (Mometasone Furoate)/Long-Acting Beta Agonist (Formoterol) Combination Compared to Step Down to Mometasone Monotherapy.

Background: Because of historical safety concerns with the use of long-acting β-agonists (LABA) in asthma, step-down from inhaled corticosteroid (ICS)/LABA combination therapy to ICS monotherapy is recommended once asthma control is achieved.

Objective: To evaluate the benefit/risk question about whether patients with asthma who achieve disease control on fixed-dose ICS/LABA combination therapy, such as mometasone furoate/formoterol fumarate (MF/F), should continue with this therapy or be stepped down to ICS monotherapy, such as MF.

Methods: Using data from 8447 clinically stable patients with persistent asthma in the Safety Pharma Investigation of Respiratory Outcomes trial who had been receiving a stable dose of ICS/LABA for ≥4 weeks, this post hoc analysis evaluated the risk of serious asthma outcomes (SAOs) (adjudicated hospitalization, intubation, or death) and asthma exacerbation (AEX) (composite of hospitalizations ≥24 hours, emergency visits <24 hours requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days) in participants randomized to remain on ICS/LABA (MF/F) or step down to ICS (MF) for 26 weeks.

Serious asthma events with mometasone furoate plus formoterol compared with mometasone furoate.

Background: The safety of long-acting β-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial.

Objective: We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340.