[Effect of ipratropium bromide on histamine-induced bronchoconstriction in subjects with chronic airway obstruction]

Ipratropium bromide (IB), a quaternary derivative of atropine has been extensively recommended as the first bronchodilator to be tried in chronic obstructive pulmonary disease (COPD). Despite the large information concerning IB use, a controversy still persists about the lack of non bronchodilator effects (preventive) of inhaled IB. Therefore, the purpose was: to study the effects of IB (80 micrograms) on histamine-induced bronchoconstriction in moderate airway obstruction due to COPD. From outpatient clinic 9 men aged (mean +/- SEM) 57.9 +/- 2.4 yr with smoking history of 54.6 +/- 5.1 pack-yrs and a mean FEV1 = 1.36 +/- 0.08 liters (47.2 +/- 3.8% predicted) were enrolled to participate in this randomized placebo-controlled double blind cross-over study. Each subject attended on 3 occasions (first visit was control day; logPC20 = -0.54 +/- 0.24 mg/ml; geometric mean [MG] = 0.27 mg/ml) for histamine challenge tests using the tidal breathing method after either 4 puffs of IB or placebo aerosol. IB significantly increased baseline FEV1. A correlation between baseline obstruction (FEV1; FEV1/FVC) and bronchodilation with airway hyperreactivity (logPC20) could not be demonstrated. The major finding was that IB attenuated the histamine-induced bronchoconstriction (logPC20 = -0.15 +/- 0.17 mg/ml; GM = 0.70 mg/ml) in comparison with placebo (logPC20 = -0.76 +/- 0.22 mg/ml; GM = 0.17 mg/ml; p = 0.018; doubling doses: IB = 2.02 +/- 0.68 vs placebo = -0.62 +/- 0.79; p = 0.024). The lack of correlation between bronchodilator response to IB and the shift in logPC20 might indicate an intrinsic protective role of IB against histamine. Both IB and fenoterol completely resolved the final fall in FEV1 after ending the histamine challenge test. In conclusion, IB diminished histamine-induced bronchoconstriction in these subjects with moderate COPD.