Am. J. Respir. Crit. Care Med., Volume 157, Number 5, May 1998, 1381-1389

Effect of Zafirlukast (Accolate) on Cellular Mediators of Inflammation
Bronchoalveolar Lavage Fluid Findings after Segmental Antigen Challenge

WILLIAM J. CALHOUN, BERNARD J. LAVINS, MARGARET C. MINKWITZ, RHOBERT EVANS, GERALD J. GLEICH, and JUDITH COHN

Division of Pulmonary, Allergy, and Critical Care Medicine, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Zeneca Pharmaceuticals, Wilmington, Delaware; and Mayo Clinic, Rochester, Minnesota

The effect of zafirlukast (Z) to alter the inflammatory response to segmental antigen challenge (SAC) was assessed by bronchoalveolar lavage (BAL) in this double-blind, placebo-controlled, two-period, crossover trial in 11 allergic asthmatic patients. Patients with asthma and positive skin tests to antigen received 7 d of treatment with Z (20 mg twice daily) or placebo (P) during two trial periods 14 to 21 d apart. At steady state (Day 5), patients underwent SAC followed by BAL immediately after challenge and 48 h later. Purified alveolar macrophages were analyzed ex vivo for phorbol myristate acetate (PMA)-driven superoxide release. Results were analyzed by analysis of variance (ANOVA). Forty-eight hours after SAC, Z therapy was associated with significantly reduced BAL lymphocytes and alcian blue-positive cells (presumably basophils) compared with P (p < 0.01), with a trend toward reduced numbers of alveolar macrophages (p = 0.06). PMA-driven superoxide release by purified alveolar macrophages was significantly reduced 48 h after SAC in the Z versus P arms (p < 0.05). Reduction of basophil influx, mediator release, and cellular activation may be important in attenuating the late phase of asthma. Collectively, the data suggest that zafirlukast therapy alters cellular infiltration and activation associated with antigen challenge.

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