Optimizing exercise for cystic fibrosis: Understanding immune modulation and identifying blood biomarkers

/ ABSTRACT Regular exercise promotes health and prevents disease, and for chronic suppurative lung diseases, like cystic fibrosis (CF), exercise serves an additional therapeutic role as an independent airway clearance technique. People with CF (pwCF) generally exhibit lower levels of physical fitness as compared to their healthy peers, such that regular exercise is recommended as part of the standard treatment regimen for CF. Beyond its physiological, functional, and psychological benefits, regular exercise is thought to exert anti-inflammatory effects and reduce infection susceptibility. Understanding how the immune modulatory effects of regular exercise influence CF disease progression, along with the underlying mechanisms, will help to determine the optimal type and dose of exercise needed to improve the overall fitness and modify the clinical course of pwCF. The proposed research project aims to 1) generate hypotheses regarding the impact of regular exercise on CF disease progression and 2) identify blood biomarkers, reflecting lung-specific responses to exercise, that can be applied to the study of human health and disease. Leveraging the Molecular Transducers of Physical Activity Consortium (MoTrPAC) young adult rat endurance exercise training dataset, in conjunction with publicly available CF and healthy control datasets, we will conduct a cross-species comparison of differentially expressed gene modules in the lungs and blood of young adult rats undergoing endurance exercise training with those in pwCF. This comparison will help to generate hypotheses about the impact of regular exercise on CF disease progression, focusing on the lungs but considering the broader impact on the entire body. We will additionally use the MoTrPAC young adult rat endurance exercise training dataset to identify a panel of sexually conserved blood biomarkers associated with lung-specific responses to endurance exercise training. The successful completion of the proposed research project will generate a set of testable hypotheses regarding the impact of regular exercise on CF disease progression and a panel of blood biomarkers to facilitate the translation of the MoTrPAC young adult rat endurance exercise training data into human studies. Project Number: 1R03AG102043-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Megan Januska | Institution: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, NEW YORK, NY | Award Amount: $84,166 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 MSOS-T (50)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11251854