The overall goal of the Human Subjects and Statistics Core is to provide biologic samples and clinical information from well-defined human subjects to enable each of the scientific projects in the AADCRC to translate their findings to the bedside. The Asthma and Airways Translational Research Unit (AATRU) at Washington University School of Medicine has a long track record of successfully recruiting human subjects and carefully characterizing these subjects with physiologic, imaging and biologic methods. This Core will eliminate duplication of effort regarding subject recruitment, collection of clinical subject data, the performance of specialized procedures such as bronchoscopy with bronchoalveolar lavage, brushings and endobronchial biopsies and initial processing of blood, BAL, and biopsy specimens. Biopsies will then be submitted to the Morphology and Microscopy Core for preparation. The Core will conduct all clinical studies and provide for subject management throughout all procedures. Accordingly, the Human Subjects and Statistics core will: I) Recruit and characterize mild to severe stable asthmatic subjects with a control group of normal and chronic bronchitis subjects for participation in the AADCRC, II) Characterize prospectively a case-controlled study of children with metapneumovirus (hMPV) bronchiolitis, using biologic, immunologic, and physiologic measures, to evaluate the determinants of recurrent persistent wheezing and subsequently, an asthmatic phenotype, and III) Maintain the AATRU Database and provide statistical analysis of data from each of the component projects and assist each project to correlate these findings with clinical data. The first protocol (Aim I) will ensure that there are adequate biologic samples on well-characterized subjects with asthma and appropriate controls. The second protocol (Aim II) will evaluate the effects of hMPV infection on airway biology during a native respiratory tract infection leading to a wheezing respiratory illness. This cohort of children will be followed over a three-yr. period to determine which ones develop persistent wheezing, a phenotype associated with asthma, following a serious hMPV infection. The molecular events in the airway triggered by viruses have not been well elucidated in vivo. This protocol will allow the individual projects l-lll to investigate molecular mechanisms and/or markers triggered in the setting of a native hMPV respiratory tract infection associated with wheezing. Furthermore, these molecular markers will be followed in this cohort over the subsequent three yrs. to assess for their persistence in those children that develop persistent wheezing. Lastly, the Human Subjects and Statistics Core will allow for the most consistent project-wide database with comparison and correlation of data, including the correlation of pathologic markers with clinical parameters (Aim III). This will enable critical findings from the AADCRC into the innate and adaptive immune signals that are central to the pathogenesis of asthma to be translated to the patient.
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