Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction.

We measured bronchoalveolar lavage (BAL) fluid histamine levels in allergic asthmatics and nonallergic normal subjects after local airway antigen and cold 22 degrees C normal saline challenges. Immediately after instillation of antigen through a bronchoscope wedged into a subsegmental airway, all 17 allergic asthmatics but none of the nine normal subjects had visible airway constriction. The asthmatics had a concomitant mean increase in BAL histamine of 23% (P = 0.005), whereas the normals had no change in BAL histamine. Among the allergic asthmatics, the change in BAL histamine content in response to antigen directly correlated with the control (baseline) BAL histamine content (r = 0.66, P = 0.003). Moreover, asthmatics with large antigen-induced changes in BAL histamine had greater airway methacholine sensitivity than did asthmatics without measurable increases in BAL histamine (8 +/- 2 vs. 41 +/- 31 breath units). Neither asthmatics nor normal subjects had airway constriction or changes in BAL histamine levels in response to nonspecific challenge with cold saline. Our data suggest that when allergic asthmatics are exposed to relevant antigens they have in vivo lung mast cell degranulation which results in airway constriction and contributes to nonspecific airway hyperresponsiveness.