Time course of increased airway narrowing caused by inhibition of deep inspiration during methacholine challenge

Inhibition of deep inspiration (DI) enhances methacholine-induced airway narrowing in normal subjects. However, the time course over which excessive airway narrowing develops during inhibition of DI is not known. We hypothesized that the development of enhanced airway narrowing when DI is inhibited is time dependent. Ten normal volunteers (five males and five females) inhaled five doses of methacholine (16 mg/ml for 2 min) at 5-min intervals during an initial methacholine challenge. FEV1 was measured at baseline and after each dose. On four subsequent days, the subjects again inhaled two, three, four, or five doses, in random order, without DIs during the challenge. FEV1 was measured only at baseline and after the last dose. Baseline FEV1 was normal in all subjects. The maximal mean percent decrease in FEV1 after the initial challenge was 10 +/- 1.5%, but was 28 +/- 6.0% when DIs were inhibited throughout the five inhalations (p < 0.01). The difference in decrease in FEV1 between days with and without DI became significant after 10 min (three doses), and remained stable thereafter when the response plateaued. The reversal of airway narrowing after three DIs was incomplete after 15 min (four doses). In conclusion, the increased airway narrowing associated with inhibition of DI during airway smooth-muscle contraction occurs after 10 min in normal subjects, at which time the response plateaus. However, the ability of DI to reverse airway narrowing appears to diminish progressively.