CAL Sub-phenotypes: A Systems Medicine Framework for Investigating Molecularly & Mechanistically Distinct Groups with Chronic Airflow Limitations (CAL) in Never-smokers

Chronic airflow limitations (CAL), which includes Chronic obstructive pulmonary disease (COPD), is a global health problem affecting 10% of the population, 20% of which have never smoked. CAL is an umbrella diagnosis, and current diagnosis based on clinical characteristics alone is not sufficient.

No cure or long-term efficacious treatment exists, and molecular descriptors of disease sub-phenotypes are desperately needed to stratify patient populations for optimal diagnosis and treatment.Alterations in epigenomes, microbiomes, mRNA, microRNA, proteomes, metabolomes, and lipid mediators from multiple anatomical locations will be quantified in 3 clinical cohorts specifically designed for systems medicine investigations of subtypes of CAL.

Data will be integrated using custom bioinformatics and biostatistics methods to identify disease sub-phenotypes. In parallel, home-monitoring using our in-house developed smartphone app as well as home-spirometry will be employed.

Biomarkers from non-invasive sampling using PExA, blood and urine will be evaluated in parallel to samples from the lung.

Mechanistic leads will be validated using organoid systems.This project aims to increase the precision of diagnosis of CAL by providing quantitative molecular profiles of disease.

Results may lead to development of new diagnostic tools and pharmaceutical targets for this debilitating spectrum of diseases, thereby reducing healthcare costs, improving quality of life, and saving lives.