ABSTRACT The overarching goals of this application are to: 1) maintain retention of children in the Vanderbilt CANOE birth cohort with emphasis on diversity and implementation of the ECHO Cohort Protocol with high fidelity and conduct new enrollment, and 2) address key questions in the field about one of the most common and modifiable early life environmental exposures consistently associated with significantly increased asthma risk, respiratory syncytial virus (RSV) infection, delineating the severity-dependent and age-dependent effects of RSV infection on asthma risk. This innovative project has significant public health impact, as establishing the age- and severity-dependent relationship between RSV and asthma is the first and most important step in disease primary prevention. We propose to address key unanswered questions in the field: the severity- and age-dependent association of RSV and asthma, and the impact of infection on lung function. In addition, we will explore the broad impact of the SARS-CoV-2 pandemic on asthma incidence and control in an exploratory aim, which may provide support for multi-faceted environmental modifications in asthma prevention and control, and data to inform the potential impact of broad public health interventions. The birth cohort that this application supports is the Vanderbilt CANOE (Childhood Allergy and the NeOnatal Environment) study. CANOE is a birth cohort designed to identify and understand how environmental factors modify the development of the airway epithelium. The study includes the unique longitudinal sampling of the child airway throughout the first year of life, and annually. The Vanderbilt CANOE study has unique early life exposure and outcomes ascertainment, including surveillance for RSV and a novel biospecimen repository of nasal airway epithelial cells. The CANOE cohort also has important information for longitudinal development of the airway microbiome and the airway epithelium. The proposed research is innovative and timely given the anticipated licensure of multiple RSV prevention products in the coming year (maternal vaccines and long- acting monoclonal antibodies for infants). The proposed work represents a novel, multi-faceted approach to identifying and understanding the influence of severity of RSV infection and age of RSV infection on asthma risk and lung function. The answers to these questions will be critical to developing prevention strategies and informing public health expectations for RSV non-pharmaceutical preventive strategies and evaluating potential long-term value-added benefits of vaccines in preventing lifelong chronic respiratory disease. These data may not only bolster RSV vaccine acceptability and uptake in the US, but will almost certainly be useful in evaluating the cost-effectiveness of RSV prevention strategies in low and middle income countries.

NARRATIVE While it is well-established that severe RSV infection is associated with later childhood asthma, delineating the severity- and age-dependent relationship of RSV infection on asthma risk and lung function is not known and is the focus of this application. The answers to these questions will be critical to developing prevention strategies and informing public health expectations for RSV non-pharmaceutical preventive strategies and evaluating potential long-term value-added benefits of vaccines in preventing lifelong chronic respiratory disease. These data may not only bolster RSV vaccine acceptability and uptake in the US but will almost certainly be useful in evaluating the cost-effectiveness of RSV prevention strategies in low and middle income countries.