Although important learnings come from traditionally designed large prospective asthma cohorts, highly restrictive inclusion and exclusion criteria limit generalisability to clinical practice. Moreover, small sample sizes for important disease subtypes, narrow scope of clinical data collection and limited biomarker assessments reduce the power of some studies to detect important and diverse longitudinal disease courses. The Real-world and Genomic data-based Asthma Insights through Network Analysis (REGAIN) study takes a novel approach to asthma cohort development by employing a pragmatic definition of asthma and simplified study procedures for biospecimen and data collection. REGAIN will produce a large scale, real-world, longitudinal clinical and molecular description of asthma powered to characterise and compare clinically relevant asthma subtypes. This design will provide insights on distinct longitudinal trajectories of disease, predictors of response to therapies and likelihood of clinical remission, all of which should help guide asthma management.

REGAIN is a clinical observational retrospective and prospective cohort study designed to determine large scale, real-world longitudinal clinical and molecular descriptions of asthma according to types of treatment, level of asthma control and inflammatory biology based on clinical biomarkers. Key questions include predictors of change in asthma control as well as timing and durability of clinical remission on biological therapy. To complement these clinical insights, REGAIN will produce one of the largest multiscale data sets in asthma that will include demographic and clinical features, inflammatory biomarkers, responses to therapy with inhaled steroids and other inhaled controllers with or without asthma biologics, and serial airway epithelium and peripheral blood transcriptomics and proteomics. REGAIN targets enrolment of 780 participants with asthma fitting one of five prespecified asthma subtypes with the aim of better characterising under-studied groups and allowing comparative analyses to elucidate important differential therapeutic responses and clinical trajectories. We target enrolment of 400 healthy controls to provide a healthy state molecular description of the tissues sampled in REGAIN participants with asthma. Participants with asthma are followed prospectively for 18 months with assessment of longitudinal clinical status including prospective clinical data collection, integration of electronic medical record data and serial biospecimen collection at 6 and 18 months. Participants with asthma starting treatment with asthma biologics undergo additional clinical assessment and biospecimen sampling at 3 months to track early clinical and molecular response to therapy. Healthy participants without asthma are evaluated cross-sectionally on enrolment without longitudinal follow-up in order to compare molecular profiles for airway epithelium and blood. An optional study component for participants with asthma employs a mobile phone application, digital inhaler monitors and home digital peak flow measurements and contributes data on real-time medication use, serial lung function and geolocated environmental data relevant to asthma.

The REGAIN protocol and all amendments were approved by The Icahn School of Medicine at Mount Sinai Program for Protection of Human Subjects (PPHS19-0358), and all participants provided written informed consent. Enrolment began in November 2019 and was completed in February 2024. Results will be presented at local, national and international meetings, and results will be submitted to peer-reviewed journals for consideration for publication.

NCT06623435.