The overall goal of this Ancillary RFA proposal is to better understand whether an imaging modality using multidetector-row CT (MDCT) chest can provide a noninvasive measure of airway remodeling in asthma. The Severe Asthma Research Program's (SARPII) central hypothesis is that severe asthma is a consequence, in part, of numerous interactive processes that lead not only to airway inflammation, injury, and altered repair mechanisms, but that there is dysregulation of selected anti-inflammatory processes that normally modulate the injury pattern leading to airway remodeling. In this proposal, we will utilize this unique resource of prospectively enrolled and carefully characterized subjects with severe asthma and appropriate comparison groups (mild- moderate asthma, normal subjects). We propose to add an Imaging protocol to SARPII that will include an Imaging Core (University of Iowa), Morphology Core (Washington University/University of Pittsburgh), and a Biostats Core (Washington University). As part of this proposal, subjects will undergo MDCT chest then bronchoscopy with guided imaging to direct where endobronchial biopsies can be obtained for the optimal sampling of a remodeled airway. We propose that validating this technology in a well- characterized cohort of adult subjects (n=200) with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. Accordingly, in order to better define whether MDCT chest can be used as a noninvasive, indirect measure of airway remodeling in severe asthma in comparison to mild asthma or normal and diseased controls, we propose the following aims: I. Standardize and assess the reliability of a common imaging protocol including both data acquisition and image analysis using MDCT in a well-characterized cohort of subjects with severe asthma in comparison to subjects with mild asthma and normal controls from the SARPII study. II. Investigate whether radiographic measures of airway thickness correlate with pathologic and physiologic markers in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. III. Investigate the use of imaging with MDCT to prospectively identify sites of airway remodeling and guide targeted bronchoscopic assessment with endobronchial tissue biopsy in subjects with mild and severe asthma and in comparison to normal controls from the SARPII study. Airway remodeling is felt to contribute to the long term decline in lung function that occurs in asthma. We propose that evaluating a new imaging technique, multidetector-row CT (MDCT) chest, in a well-characterized group of subjects with severe and mild asthma and normal subjects will provide a valuable, clinically useful, noninvasive measure of airway remodeling. This measure of airway remodeling may help identify individuals with asthma who are likely to develop severe disease and who may benefit from early targeted, aggressive therapy.
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