This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Asthma is a heterogeneous disease in adults, with some expressing mild disease, whereas others have severe symptoms. Some adults with asthma progress to severe irreversible airway obstruction, whereas other maintain airway function. The investigators have identified a large cohort of patients with atopy and persistent airway obstruction in their urban clinic of adult patients with asthma. The question arises, therefore, whether in the atopic subject with asthma, there are disease modifying genes that predispose to the development of irreversible airway obstruction. The global aim of this proposal will be to test the hypothesis that in a susceptible host, there are disease-modifying genes that modulate the response to the repetitive allergic inflammatory injury. The focus will be to define precise physiologic phenotypes of severe asthma and to test the association between allelic variants in airway/matrix remodeling genes and the defined severe phenotypes. More specifically, the study's aims are as follows: 1) To identify specific physiologic phenotypes of 'severe asthma' defined by spirometry, plethysmography and measurement of elastic recoil properties of the lung. 2.)To test the hypothesis that asthma susceptibility as determined by IgE (total and allergen-specific) discriminates the physiologic phenotypes of severe asthma. 3) To test the hypothesis that polymorphisms of matrix remodeling genes are associated with physiologic phenotypes of severe asthma (disease-modifying genes).
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