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, Judith Cohn

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

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 immedidately 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 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.

Original languageEnglish (US)
Pages (from-to)1381-1389
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume157
Issue number5 PART I
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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