Related Experiment Video

Updated: Jun 13, 2025

Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples

Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples

Published on: May 21, 2021

Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised,

James D Chalmers¹, Michal Shteinberg^2,3, Marcus A Mall^4,5,6

¹Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK j.chalmers@dundee.ac.uk.

The European Respiratory Journal

|September 10, 2024

Abstract

Background:

Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF^®; clinicaltrials.gov identifier NCT05238675) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.

Methods:

In total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1 mg/2.5 mg/5 mg) or placebo for 24-48 weeks. A multiple comparison procedure and modelling approach was used to demonstrate a nonflat dose-response curve based on the time to first pulmonary exacerbation up to week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and/or intravenous antibiotic administration), lung function and quality of life.

Results:

A significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: maximum effect curve 1; adjusted p=0.0448). Treatment with BI 1291583 5 mg and 2.5 mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratio (95% CI) 0.71 (0.48 to 1.05) and 0.66 (0.40 to 1.08), respectively; both p>0.05). BI 1291583 2.5 mg showed numerically better efficacy compared with 5 mg across several end-points; 1 mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.

Conclusion:

Treatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.

More Related Videos

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung

Published on: January 22, 2021

Real-Time, Semi-Automated Fluorescent Measurement of the Airway Surface Liquid pH of Primary Human Airway Epithelial Cells

Real-Time, Semi-Automated Fluorescent Measurement of the Airway Surface Liquid pH of Primary Human Airway Epithelial Cells

Published on: June 13, 2019

Related Concept Videos

Cystic Fibrosis: Management

Cystic Fibrosis: Management

Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...

COPD: Management Using Bronchodilators and Corticosteroids

COPD: Management Using Bronchodilators and Corticosteroids

Chronic obstructive pulmonary isease (COPD) involves a group of progressive lung disorders characterized by persistent airflow limitation and chronic respiratory symptoms. Asthma-COPD Overlap Syndrome (ACOS), encompassing features of both asthma and Chronic obstructive pulmonary disease (COPD), is a group of progressive lung disorders that includes chronic bronchitis, emphysema, and refractory (non-reversible) asthma. ACOS leads to complex clinical presentations that combine the inflammatory...

Cystic Fibrosis: Pathogenesis

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation

Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids

Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids

Inhaled corticosteroids (ICS) are anti-inflammatory drugs used primarily in treating persistent asthma and providing long-term maintenance. They target the bronchial mucosa, the lining of the airways, to control inflammation, a critical factor in asthma progression and exacerbation.
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...

Antiasthma Drugs: Leukotriene Modifiers

Antiasthma Drugs: Leukotriene Modifiers

Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:

Articles linked to this work by shared authors, journal, and citation graph.

Preventive intrapulmonary treatment with Ligilactobacillus murinus reduces airway inflammation and mucus plugging in mice with cystic fibrosis-like lung disease.

ERJ open research·2026

Efficient AI-supported quantification of network structures in SEM imaged human mucus: a detailed protocol.

American journal of physiology. Lung cellular and molecular physiology·2026

The association between chronic rhinosinusitis, bronchiectasis and type 2 inflammation: an EMBARC registry analysis.

ERJ open research·2026

Bridging the airway microbiome and targeted therapy in bronchiectasis: multi-omics insights, endotypes and emerging therapies.

The European respiratory journal·2026

Bronchiectasis in Italy: an analysis of the EMBARC registry.

ERJ open research·2026

Investigating sarcopenia and mucus plugging by chest computed tomography in patients with severe chronic obstructive pulmonary disease.

Scientific reports·2026

See all related articles