Study of Airflow Limitation in Non-Smoking Adults and Teens with Moderate to Severe Asthma Evaluating Treatment Effects of Inhaled Corticosteroids and Bronchodilators

What this Trial Is About

This research aims to understand the causes and sites of expiratory airflow limitation in people with moderate to severe persistent asthma who are stable, treated, and non-smokers. The study focuses on whether airflow limitation mainly occurs in large or small airways and how much is due to airway obstruction or loss of lung elastic recoil. Researchers will use markers like exhaled nitric oxide to assess airway inflammation and will also study lung changes during asthma flare-ups and stable periods, including detailed imaging and tissue analysis when available. Participants will receive treatment with one of three inhaled corticosteroid and long-acting beta2-agonist combinations fluticasonesalmeterol, budesonideformoterol, or mometasoneformoterol, combined with tiotropium daily. For acute flare-ups, albuterol and ipratropium will be used as needed. The study includes measurements of lung function and quality of life questionnaires. Imaging such as high-resolution CT scans and optical coherence tomography will be performed to evaluate lung structure and detect emphysema. During the study, participants will undergo tests including spirometry with special gas mixtures to locate airflow limitation and exhaled nitric oxide measurements to monitor inflammation over 20 to 60 days. Researchers will also analyze lung tissue from autopsies or transplants when available. The main outcomes include assessing airway inflammation, airflow limitation sites, lung elastic recoil loss, and the presence and extent of emphysema. The study runs until June 2027, with detailed evaluations during stable periods and exacerbations.

Mechanism(s)of Airflow Limitation in Moderate-severe Persistent Asthma