Approach to Predict Steroid Sensitivity in Patients With Asthma

Inhaled corticosteroids are widely used as the primary therapy for asthma, which affects approximately 20 million people in the United States. While many patients respond to corticosteroid therapy, as many as 25-30% of patients with severe asthma have asthma that is difficult to treat or steroid insensitive. Predictive biomarkers for the rapid identification of patients with asthma who will achieve adequate control of their symptoms with inhaled corticosteroids has the potential to significantly improve asthma management. This proposal is based on the hypothesis that alterations in gene expression in epithelial cells of the buccal mucosa can be used as a reliable biomarker to predict corticosteroid response in patients with asthma. The goals of this proposal will determine if gene expression in epithelial cells of the buccal mucosa from patients with asthma is in concordance with gene expression profiles that have been identified through more invasive sampling techniques of the airway epithelium of asthma patients. The Specific Aims of this proposal are to 1) investigate the level of variability in gene expression of a subset of inflammatory markers in buccal epithelium from adult patients with asthma. Aim 1 will be carried out by collecting buccal samples from three cohorts of subjects (18-55 years of age) from the Pulmonology and Allergy Clinics at Truman Medical Center during regularly scheduled outpatient visits as follows: 1) healthy control adult subjects (n=10), 2) patients with asthma treated only with a short-acting beta2-agonist (SABA, n=10), and 3) patients with asthma treated with low-dose ICS (n=10). Relative gene expression of inflammatory markers will be determined using quantitative RT (reverse transcription)-PCR and variability in gene expression will be determined within and between the three cohorts. Data from the pilot studies described in this proposal will aid in the determination of appropriate study population sizes for future investigations with the long-term objective to use changes in gene expression (in buccal epithelial cells) as a dynamic biomarker for determining corticosteroid response in patients with asthma.