IMPORTANCE OF THE TIME INTERVAL BETWEEN FEV1 MEASUREMENTS IN A METHACHOLINE PROVOCATION TEST

We examined the hypothesis that a forced expiratory volume in one seco nd (FEV1) manoeuvre (and the preceding deep inhalation) before inhalat ion of methacholine might influence FEV1 measured after methacholine, if the time between measurements was short. Six to nine healthy subjec ts inhaled a single dose of methacholine, known to cause about 20% dec rease in FEV1, on different days in different test protocols. If an FE V1 manoeuvre was performed immediately before methacholine, the first FEV1 measured 3 min after provocation was higher (77% of basal FEV1) t han if a pre-methacholine FEV1 manoeuvre was not performed (64%). This effect of a pre-methacholine FEV1 manoeuvre was also demonstrated at 2, 4 and 6, but not at 10 min after the start of methacholine inhalati on. If an FEV1 manoeuvre was not performed before methacholine, the se cond and subsequent FEV1 measured in constricted airways was higher th an the first, and of similar magnitude to the first FEV1 in tests wher e a pre-challenge FEV1 manoeuvre was performed. In another trial, 10 h ealthy subjects performed two stepwise methacholine tests, with either 6 or 3 min between dose steps. The percentage decrease in FEV1 per mg of inhaled methacholine decreased from 2.6 (1.9-5.2) to 1.7 (0.8-2.3) (median, interquartile-range) when the time interval was shortened. T he results suggest that the deep inhalation associated with the FEV1 m anoeuvre decreases the bronchial tone in airways constricted by methac holine for up to 6 min, possibly due to yielding of cross-links in air way smooth muscles.