This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this investigation is to determine the influences of treatment with fluticasone and salmeterol on smooth muscle alterations in asthma at the biochemical level, and to relate these findings to genotype at selected gene loci. The overall hypothesis is that treatment with these agents quantitatively and/or qualitatively alters asthmatic smooth muscle, in the amounts and types of protein and/or RNA species present, and that such responses to treatment may relate to genetic variations at selected gene loci.
Our specific aims are to: (i) obtain endobronchial biopsies from subjects with mild, persistent asthma for laser capture microdissection prior to and immediately following 4 weeks of treatment with inhaled fluticasone and salmeterol or neither in a placebo-controlled, double-blind fashion; (ii) analyze the smooth muscle compartment, or other airway compartments, for protein and/or RNA species contents, using western analysis, gene profiling, real-time PCR, and other methods as they become available; (iii) compare these biochemical profiles between pre-treatment and post-treatment samples, and determine whether treatment type influences any pre- to post-treatment differences found; and (iv) relate biochemical findings to genotypes at selected gene loci, using a venous blood sample to provide DNA for genetic analysis
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