Air pollution sensitivity in pediatric asthma - Ambient air pollution (AAP) exposure is a trigger for pediatric asthma exacerbations, significantly contributing to asthma related morbidity. While reducing AAP exposure is a long-term public health imperative, there is an urgent need for strategies to predict and prevent asthma exacerbations in children exposed to AAP. To address this critical gap, this project will leverage emerging opportunities in data science, aligning with the National Heart, Lung, and Blood Institute’s (NHLBI) Objective 7 to open new frontiers in heart, lung, blood, and sleep research. By integrating clinical, genetic, social, and environmental data, this project will assess individual susceptibility to AAP and develop predictive models for asthma outcomes. Preliminary data from Dr. Jelte Kelchtermans, Instructor at the University of Pennsylvania and attending physician in Pulmonary and Sleep Medicine at the Children’s Hospital of Philadelphia, identified a subgroup of pediatric patients with heightened sensitivity to AAP who experience increased asthma morbidity. This subgroup demonstrates specific genetic variants associated with exacerbation risk and reduced lung function under high AAP exposure, highlighting the influence of genetic predisposition in shaping AAP sensitivity. Building on these findings, this project will address two primary aims. In Aim 1, Dr. Kelchtermans will investigate how clinical, genetic, and social variables interact with short-term AAP variations to influence exacerbation incidence, with a focus on refining a polygenic risk score for AAP sensitivity, exploring gene-gene interactions, and developing predictive models validated with the All of Us cohort. In Aim 2, he will examine how these variables shape long-term lung function attainment in children genetically predisposed to AAP sensitivity, using longitudinal data to model lung function trajectories and interactions with clinical and social factors. The Center for Applied Genomics and the Center of Excellence in Environmental Toxicology provide an exceptional environment for this research, with mentorship from experts, including primary mentors Dr. Hakon Hakonarson and Dr. Sharon McGrath-Morrow and advisory members Dr. Joseph Glessner, Dr. Kim Dokyoon, Dr. Blanca Himes, and Dr. David Hill. This project aligns with NHLBI’s objectives and represents a critical step toward actionable interventions in pediatric asthma care. In conclusion, the proposed research offers Dr. Kelchtermans a unique opportunity to advance toward scientific independence while transforming population-level associations into individualized clinical tools for proactive and preventive asthma management.
