DISSIMILARITY IN METHACHOLINE AND ADENOSINE 5'-MONOPHOSPHATE RESPONSIVENESS 3-H AND 24-H AFTER ALLERGEN CHALLENGE

Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5'-monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with hose dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was inhaled, and methacholine or AMP challenge was performed 3 h later. The next day HDM was inhaled, and 3 and 24 h later methacholine or AMP challenge was performed again. There were no significant differences in FEV1 baseline values between any of the study days. PD20 HDM, percentage decrease in FEV1, and AUC for both the EAR and LAR were not significantly different in the methacholine and AMP studies. After HDM challenge, PC20 methacholine decreased significantly from a geometric mean (+/- SEM) starting value of 1.39 +/- 0.63 mg/ml to 0.30 +/- 0.78 mg/ml (p <0.001) at 3 h and to 0.22 +/- 0.75 mg/ml (p <0.001) at 24 h. The magnitude of the decrease in PC20 methacholine at 3 h correlated with the severity of the late asthmatic reaction (LAR) as measured by the percentage fall in FEV1 and area under the curve (AUC) (r = -0.60 and r = 0.55; p <0.05). A significant decrease was observed in the PC20 AMP at 3 h, from a geometric mean value of 12.2 +/- 0.96 mg/ml after challenge with the control solution to 4.47 +/- 0.99 mg/ml (p <0.05) after HDM challenge. In contrast to methacholine, no significant decrease could be demonstrated with AMP for the PC20 at 24 h (10.85 +/- 1.07 mg/ml; p > 0.05). No correlation between the decrease of the PC20 AMP and the severity of the LAR could be demonstrated. The difference in decrease after HDM challenge between the PC20 methacholine and the PC20 AMP at 24 h was significant (p <0.05). We conclude that BHR, as measured with a direct (methacholine) and an indirect (AMP) stimulus, increases 3 h after HDM challenge. This increase is correlated with the severity of the LAR only if measured with methacholine. A significant increase in allergen-induced BHR at 24 h was measured with methacholine, whereas the PC20 AMP had almost returned to prechallenge values. Together these observations suggest that the increase in BHR precedes the late asthmatic response and that several mechanisms may be involved in the allergen-induced increase in BHR after allergen challenge.