ASSESSMENT OF BRONCHOALVEOLAR CELL AND MEDIATOR RESPONSE TO ISOCAPNIC HYPERPNEA IN ASTHMA

The purpose of this study was to test the hypothesis that mediators and cells associated with bronchoconstriction or inflammation are locally synthesized and/or released in the airways of asthmatic subjects in response to isocapnic hyperpnea (ISH). Seven atopic, mildly asthmatic subjects were studied. Baseline measurements were reported previously and included forced expiratory volumes, flow rates, bronchoalveolar lavage (BAL), and methacholine reactivity. Approximately 1 yr later, spirometry and BAL were repeated, but BAL was performed immediately after ISH challenge. As indices of inflammation, BAL measurments were made of eosinophils, neutrophils, epithelial cells, leukotrienes B4, C4, D4, and E4, prostaglandin D2, E2 and F(2α), thromboxane B2, histamine, and total protein. Compared with baseline, ISH was associated with higher BAL concentrations of the following: leukotriene B4 (10 versus 121 pg/ml, p = 0.02), leukotrienes C4/D4/E4 (46 versus 251 pg/ml, p = 0.02), eosinophils (0.8 versus 2.2%, p = 0.04), and epithelial cells (2.1 versus 6.1%, p = 0.05). Trends toward significant increases were seen in BAL concentrations of neutrophils and prostaglandin D2. No statistically significant increases were found in BAL measurements of total protein, histamine, prostaglandins E2 or F(2α) thromboxane B2 lymphocytes, or macrophages. The magnitude of the response to ISH, as measured by change in FEV1, did not correlate with BAL levels of cells or mediators. This study indicates that ISH, even in mildly asthmatic subjects, is associated with airway increases in a spectrum of bronchoactive mediators and inflammatory cells, supporting the observations of others that antagonists of a single mediator are unlikely to have major clinical effectiveness in ISH or exercise-induced asthma.