Effect of ipratropium bromide on EIB in children depends on vagal activity

Ipratropium bromide (IB) has been used to prevent exercise-induced bronchoconstriction (EIB), but its effect varies among individuals. We hypothesized that such variability may reflect individual differences in vagal activity (VA), and therefore determined whether a correlation exists between VA and the effect of IB on EIB in 13.0 (+/-0.8)-yr-old children with asthma and documented EIB. Subjects served as their own control and were tested on three occasions in an ambient temperature of 5 degrees C. Visit I included no treatment. In visits II and III (counterbalanced sequence) subjects inhaled either 500 microg IB or 0.9% NaCl as a placebo, 45 min before exercise provocation. Investigators and the subjects were blinded to the inhaled substance. VA was assessed by a 4-s exercise test (3). The ratio of resting ECG R-R-interval at full inspiration to the lowest R-R interval during 4-s cycling was taken as an index of VA. Eight-minute cycling at constant work rate (HR=173+/-4 bpm) at 5 degrees C was used to provoke EIB. A two-factor (treatment x time) repeated-measures ANOVA was used. The exercise-induced drop in FEV1 was similar in the three sessions. However, because the IB caused a 15.7+/-4.1 increase in FEV1 preexercise, the postexercise values after a placebo or no treatment were consistently lower than after IB. The beneficial response to IB, compared with no treatment and with placebo, was positively correlated to VA (for FEV1: r=0.91, P=0.002; and r=0.90, P=0.002, respectively). We suggest that the therapeutic effect of IB on exercise-induced asthma may be related to vagal activity.