The overall goal of this Asthma and Allergic Diseases Cooperative Research Center (AADCRC) proposal is to elucidate the mechanisms by which the innate immune system affords protection against viral-induced exacerbations in asthma. In the renewal of our AADCRC program, we will continue to focus on the critical and often understudied innate immune factors the anion lipids of surfactant, (palmitoyl-oleoyl- phosphatidylglycerol (POPG) and phosphatidylinositol (PI)) and Toll interacting protein (Tollip) and surfactant protein-A (SP-A). Three inter-related projects are proposed in this application; the program will employ use of biologic airway and peripheral systemic specimen samples obtained from well-phenotyped participants with and without type 2 asthma and atopy through Core B, the Clinical Core. We hypothesize that POPG/PI, Tollip and SP-A function as unique immune modulators which attenuate the effects of viral infections in type 2 asthma, specifically RV-C, influenza A and SARS-CoV-2. Supplementation of functional POPG/PI, SP-A and the IL-33 decoy receptor sST2 offer novel alternatives to reduce exacerbations due to viral infections in asthma. Use of human samples is critical as animal models of SARS- CoV-2, influenza and RVC are limited, and translational of findings to human disease can be variable. Therefore, the goal of the Clinical Core is to provide services for our AADCRC investigators to perform safe, consistent procedures in research participants for phenotyping and standardized, high quality collection of biologic airway and peripheral systemic specimens, cost effective sample processing and data collection, with robust data management and statistical analysis to test the hypotheses presented in each project. This Clinical Core will extensively phenotype 100 participants comprised of 60 asthma (30 mild, and 30 severe) patients and 40 controls (25 atopic, 15 non-atopic) for lung function testing, type 2 phenotyping, genotyping, nasal sampling, and to participate in the bronchoscopy studies to understand the effectiveness of these innate immune modulators in asthma and atopy, and in mild and severe asthma. The Clinical Core will coordinate and perform bronchoscopy with bronchoalveolar lavage, nasal and epithelial cell brushings, and endobronchial biopsy on all participants. The Clinical Core will be responsible for processing, storing, and distributing all samples collected from participants, to each of the three projects. In this capacity, the Core will allow each clinical sample to be utilized to its full potential and serve all projects equally. For all of the studies within the AADCRC utilizing human subject samples, the Clinical Core will also be responsible for assuring patient safety, data confidentiality and full regulatory compliance. A Biostatistics Unit is embedded in this core to integrate the clinical data with the molecular/biomarker data to effectively model relationships between cellular features and clinical phenotypes ...