PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding the extent to which the school environment contributes to respiratory virus exposure, and less is known about potential environmental interventions to reduce exposure. Our long-term goal is to create healthy indoor school environments for children. The overall objective of this application is to identify modifiable factors of respiratory virus exposure in elementary schools in order to reduce asthma morbidity. We will combine novel approaches to quantify and characterize the respiratory virome in schools by leveraging the robust infrastructure of the School Inner-City Asthma Intervention Study (SICAS-2, ClinicalTrials.gov NCT02291302), a randomized controlled trial conducted by our group of a placebo-controlled classroom high efficiency particulate air (HEPA) cleaner intervention. We will test our central hypothesis that schools are a source of high respiratory virus exposure that affects asthma morbidity through the following specific aims: (1) To compare respiratory virus exposure in schools as compared to homes by using a hybrid capture panel to recover genomes of detected respiratory viruses; (2) To identify factors predicting respiratory virus exposure in schools including the efficacy of portable HEPA cleaners in reducing classroom respiratory virus exposure; (3) To determine the association between the classroom respiratory virome and asthma symptoms in elementary school children. The approach is innovative, because we are simultaneously interrogating all major human respiratory viruses in the school environment. The proposed research is significant, because it will identify the magnitude of exposure to respiratory viruses in schools and potential environmental factors that can serve as future targets of intervention. If the HEPA intervention can reduce respiratory virus exposure, it is an immediately actionable and practical intervention to create safer indoor environments for elementary school children. Results from this proposal may be generalizable to other public indoor settings.