Resident Physician University of Colorado School of Medicine Denver, Colorado, United States
Background: Wheezing episodes are clinically heterogeneous in severity and response to treatment. Namely, some resolve with minimal intervention, while others require emergency care, with the most severe illnesses necessitating hospitalization. The factors that underlie this heterogeneity in outcomes are unclear, but likely relate to the viral pathogen triggering the illness and the host airway immune response (i.e., endotype). Objective: To elucidate the viral pathogens and host endotypes underlying severe wheezing episodes requiring hospitalization among young children, and to uncover the dynamics of patient endotype expression and viral infection during hospitalization for recurrent wheeze. Design/Methods: Toddlers aged 18-36 months old with recurrent wheeze (at least one prior wheezing episode) were enrolled during an emergency department (ED) visit for wheezing illness in the WINDOWS study (Critical Windows in the Development of Asthma Endotypes and Phenotypes in High-Risk Toddlers) with IRB approval (Fall 2022-Fall 2023). Children were either Medicaid-enrolled or living in urban-poor census track. In 29 participants, nasal epithelial cells were collected with flocked swabs in the ED, 24 hours after hospital admission, and at discharge if length of stay exceeded 24 hours. RNA extracted from nasal samples will be used for whole-transcriptome RNA sequencing and analyzed to characterize gene expression networks, which will include airway inflammatory and mucosal immune response networks. Viral infection, species, and load will be determined analyzing RNA-seq with the VirProf viral metagenomic pipeline. Changes in inflammatory endotype, immune responses, and viral infection between timepoints will be evaluated to identify important dynamics in these parameters underlying hospitalization and resolution. Regression models will be used to assess associations between airway endotype, viral infection, and severity of wheezing episode. All samples have been collected and analysis will be completed before April 1, 2024.
