Novel mediators of eicosanoid and epithelial nitric oxide production in asthma - GSE13785

Exercise-induced bronchoconstriction (EIB) is a distinct syndrome that occurs in 30-50% of asthmatics and is characterized by high levels of pro-inflammatory eicosanoids. We identified genes differentially expressed in the airways of asthmatics with EIB relative to asthmatics without EIB.

Subjects 18-59 years of age were recruited who had a physician diagnosis of asthma for = 1 year, and used only an inhaled beta2-agonist for asthma treatment. In accordance with a priori definitions, asthmatics with a methacholine PC20 = 4 mg/ml were identified with = 20% fall in FEV1 following exercise challenge (EIB+ group) and asthmatic controls without EIB were identified with = 5% fall in FEV1 following exercise challenge (EIB- group). Potential participants were excluded if baseline FEV1 was = 65% predicted, history of smoking cigarettes within the prior year or = 7 pack-year smoking, treated for acute asthma within the prior month, hospitalized for asthma within the prior 3 months, or history of life threatening asthma. Participants were excluded if they had used an inhaled or oral corticosteroid, leukotriene modifier, long-acting antihistamine, cromone, or long-acting beta2-agonist in the 30 days prior to the study. Comparisons were also made to non-asthmatic subjects with negative methacholine (PC20 > 8 mg/ml) and dry air exercise challenge tests (< 20% fall in FEV1 following exercise).

EIB and exercise

EIB negative subjects

Epithelial brushings and endobronchial biopsies were obtained from subjects with asthma and EIB defined by a methacholine PC20 = 4 mg/mL and = 15% fall in FEV1 following exercise challenge. Some epithelial brushings from asthmatics were placed in primary culture and used at passage 1 or 2 for in vitro experiments as detailed in the supplemental material.