CanMuc: A Canadian consortium-led longitudinal observational study on the role of airway mucus in asthma, chronic obstructive pulmonary disease and chronic cough

BACKGROUND Asthma, chronic obstructive pulmonary disease (COPD) and chronic cough (CC) significantly burden the Canadian healthcare system. Despite therapeutic advances, many patients remain symptomatic, and symptom-based management strategies have modest effects. Airway mucus may contribute to disease severity and outcomes; however, its role remains underexplored.OBJECTIVE The primary objective of the Canadian Consortium (CanMuc) is to measure airway mucus, rheology and inflammation and uncover relationships of the imaging and physico-biological characteristics of airway occlusions in asthma, COPD and CC compared with healthy controls. Secondary objectives include assessing biomarkers leading to persistent mucus.METHODS In this 24-month, longitudinal, multi-center, observational study, 240 participants with pulmonary disease (100 moderate-to-severe asthma, 80 COPD, 60 CC) and 100 healthy volunteers (≥18 years) will be recruited across 6 Canadian tertiary-care sites. Participants will undergo chest CT, blood and sputum collection, rheology, spirometry, oscillometry, cough monitoring, validated respiratory questionnaires and cough severity assessments. At 3 sites hyperpolarized 129Xe MRI will be performed. Quarterly telemonitoring will document exacerbations, hospitalizations, and symptoms or treatment changes. CT mucus burden (score, count, volume, radiodensity), mucus rheology (viscosity, elasticity, viscoelasticity) and inflammatory pathways will be analyzed. Participants will be classified into 4 phenotypes at end-of-study: mucus-free, persistent, resolved and new-onset. Secondary outcomes include evaluating clinical, physiological and molecular markers predicting airway mucus occlusions.CONCLUSIONS The CanMuc study will evaluate the contribution of airway mucus occlusions to the severity and worsening of chronic airways diseases using imaging, immunologic, molecular and rheological characterization. Findings will provide multi-center evidence and validate airway occlusions as a potential treatable trait.