The Clinical Core will be responsible for all human subject-related activity for the AADRC program. This Core has four main functions: (a) recruitment and characterization of human subjects; (b) performance of bronchoscopy, along with allergen or kinin challenge, bronchial biopsy, bronchial brushing, or bronchoalveolar lavage as required; (c) collection of blood or blood cells; and (d) microdissection of bronchial biopsies and lung samples. The study of animal models of asthma or in vitro model systems has resulted in significant progress towards elucidating the immunology and cellular and molecular biology of asthma. Despite these successes, any effort to understand clinical asthma (or how asthma is initiated and propagated) must ultimately be undertaken or validated by studying human subjects with asthma. These human studies, however, are subject to considerable difficulty, including problems recruiting appropriate subjects, the clinical heterogeneity of asthma and the difficulty in obtaining suitable clinical material for study. A highly specialized and independent Clinical Core has been designed for this AADRC program to remove the burden from investigators of the consuming tasks of human subject recruitment/characterization and bronchoscope/sample acquisition while simultaneously supplying all investigators with sufficient clinical samples to efficiently pursue the mechanistic studies that define each project. By utilizing a common core to recruit, screen and study volunteer subjects, all investigators participating in this AADRC program will have full access to the subject-derived samples, independent of whether the investigators have an appropriate clinical background. In addition, expertise of the Clinical Core and standardization in sample preparation will contribute to insuring the most consistent and highest quality samples possible. Performing bronchoscopy with lavage and biopsy in asthmatic subjects has revolutionized our understanding of the pathophysiology of asthma, leading to the recognition that airway inflammation is present in even mild asthma and pointing toward the role of airway remodeling in chronic asthma. Bronchoscopy procedures have not, however, yielded information that can be used to predict asthmatic phenotype. This program will link genetic, cellular, and biochemical findings obtained from patients? samples using state-of-the-art laboratory techniques to carefully documented asthma phenotypes, potentially allowing novel insights into the determinants of asthmatic phenotype to be gleaned.
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