Increases in airway responsiveness to histamine precede allergen-induced late asthmatic responses

Changes in airway responsiveness to histamine after allergen inhalation challenge were studied in 14 nonsmoking atopic adult subjects with asthma. Inhalation challenges with allergen and with phosphate-buffered saline (control challenge) were performed single blind in random order, with an interval of 14 days. The development of a late asthmatic response was accompanied by an increase in airway histamine responsiveness that was significant when it was compared with the airway histamine responsiveness after the control challenge at 3 hours ( p < 0.01), 24 hours ( p < 0.01), and 48 hours ( p < 0.02), with recovery at 2 weeks after allergen inhalation. The 3-hour changes in airway responsiveness occurred independently of changes in airway caliber and correlated with the magnitude of the subsequent late response ( r = 0.86; p < 0.001). These results suggest that the tissue events (possibly airway inflammation) that underlie the late asthmatic response may occur before this response becomes clinically apparent.