Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 910-916

Deep Inspiration-induced Bronchoprotection Is Stronger than Bronchodilation

NICOLA SCICHILONE, TRISEVGENI KAPSALI, SOLBERT PERMUTT, and ALKIS TOGIAS

Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland

We have previously shown that in healthy subjects, deep inspiration (DI) has not only a bronchodilatory but also a bronchoprotective effect that is absent in asthmatic subjects. We conducted the study reported here to test the hypothesis that the bronchoprotective effect is stronger than the bronchodilatory effect, and to determine the extent to which these two effects are related. Ten healthy subjects underwent provocations in which single doses of methacholine, previously shown to reduce FEV₁ by 10% to 20% (Dose 1) and by 20% to 40% (Dose 2) were administered after a 20-min period devoid of DI. To measure the bronchodilator effect, DIs were performed immediately after the first spirometry after methacholine, and were followed by another lung function test. To measure their bronchoprotective effect, DIs were performed before administration of a single dose of methacholine, and the FEV₁ after methacholine was compared with that of another single-dose challenge in which DIs were not included. From these outcomes, bronchodilation and bronchoprotection indices were constructed and compared with each other. At Dose 1 (mild obstruction), the ability of DIs to reverse methacholine-induced obstruction was equal to their ability to prevent it (bronchodilation index [BDI] versus bronchoprotection index [BPI]: 1.62 ± 0.21 versus 2.02 ± 0.40 [mean ± SEM], p = 0.26). At Dose 2, the relative potency of both the bronchodilating and bronchoprotective effects of DIs increased, but bronchoprotection was significantly stronger (BDI versus BPI: 3.40 ± 0.43 versus 6.98 ± 1.42, p = 0.02). Correlation analysis of the two indices indicated that as the BPI increased, the BDI reached a plateau. We conclude that in healthy humans, the bronchoprotective effect of lung inflation is stronger than the bronchodilatory effect.

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