Airways are More Reactive to Histamine than to Methacholine in Patients with Mild Airway Hyperresponsiveness, Regardless of Atopy

BACKGROUND: The airway muscles from allergen-sensitized animals in vitro show a heightened response to histamine, but not to carbachol. This study investigated whether the airway responsiveness to histamine in vivo is comparable to that of methacholine in human subjects with varying degrees of atopy. METHODS: One-hundred-and-sixty-eight consecutive adult asthma patients or volunteers underwent bronchoprovocation tests to both histamine and methacholine after determining their blood eosinophil counts, serum total IgE levels and skin test reactivity to 10 common aeroallergens. RESULTS: The responsiveness to histamine was significantly related to that to methacholine (r=0.609, p<0.001), but many individuals with a negative methacholine test response showed a positive response to histamine. The histamine-bronchial reactivity index (BRindex) was significantly higher than the methacholine-BRindex in subjects with a positive response to none (n=69, p<0.01) or only one (n=42, p<0.001) of histamine and methacholine, while there was no significant difference in the subjects with positive responses to both of them (n=57). The histamine-BRindex was significantly higher than the methacholine-BRindex in the subjects with mild histamine hyperresponsiveness (n=58, 1.28+/-0.01 vs. 1.20+/-0.02, respectively, p<0.001). Both histamine and methacholine responsiveness was significantly related to the atopy markers. However, the histamine-BRindex/methacholine-BRindex ratio of the atopics was not significantly different from that of the non-atopics. CONCLUSIONS: The airway responsiveness to histamine is comparable to that of methacholine in the subjects with positive responses to both histamine and methacholine, but the airway responsiveness to histamine is greater than that to methacholine in those subjects with mild airway hyperresponsiveness, regardless of atopy.