PROJECT SUMMARY/ABSTRACT Wheezing is a highly prevalent symptom among preschool children that is notoriously difficult to treat. While the factors associated with wheezing are complex, it is also recognized that preschool children are a heterogeneous group, with differing symptom profiles that may contribute to differing clinical outcomes and disease trajectories. However, symptom science is quite limited in preschool children and has focused primarily on respiratory symptoms in isolation, ignoring other physical symptoms and symptoms of mental and social health in caregivers that are important to overall functional status and quality of life. To date, there has been no attempt to identify or study symptom clusters (defined as two or more concurrent symptoms independent of other clusters) in preschool children with recurrent wheezing. This K24 application entitled “Mentored Patient-Oriented Research in Preschool Wheezing Disorders” seeks five years of support for protected time to expand the Principal Investigator’s mentoring activities, promote her career development and provide momentum to advance her research on symptom clustering in preschool children with recurrent wheezing. The Principal Investigator has built an extensive research program on preschool wheezing in an environment with unparalleled infrastructure, resources and collaborators. Career Development goals are to ensure that the Principal Investigator will be provided sufficient time for mentoring and patient-oriented clinical research activities. The award will also allow the Principal Investigator to further her education in statistical methods and study design, molecular biology, and precision medicine to help her expand her patient-oriented research program. This training will also facilitate the design of interventions to reduce the severity and incidence of wheezing in young children. The overarching research hypothesis is that symptom clusters and their associated inflammatory pathways predict clinical outcomes in preschool children age 12-59 months with recurrent wheezing. Specific aims are to determine whether symptom cluster predicts exacerbation (primary outcome) and quality of life (secondary outcome) and to utilize next-generation sequencing to identify pathways underlying symptom clusters and their trajectories. This project addresses innovative questions in symptom science and may result in identification of novel biomarkers for personalized intervention. Greater understanding of symptoms underlying morbidity will also help tackle a critical public health problem (wheezing) that affects a growing proportion of children in the United States.