REFRACTORY PERIOD DURING PROVOCATION WITH EUCAPNIC HYPERVENTILATION AND METHACHOLINE

Eucapnic voluntary hyperventilation (EVH) and methacholine inhalation challenge (MIC) both cause bronchoconstriction in asthmatics. A refrac tory period, or time when the response to bronchoprovocation in a seri es of challenges is diminished, has been found after hyperventilation or exercise but not after MIC. We investigated whether EVH or MIC blun ted the response to the other test. Sixteen asthmatics were studied on 2 d, taking both tests each day. They were randomized to either EVH o r MIV first on Day 1, then the opposite order on Day 2, 6 to 14 d apar t. After EVH as a first test, the mean decline in FEV(1) from base-lin e was 18.66 +/- 4.76% (mean +/- SEM), but when EVH followed MIC, the r esponse to EVH was reduced by 30%, to a decline in FEV(1) of only 13.0 2 +/- 3.75% (p = 0.0026). During MIC, the mean provocation dose to cau se 20% decrease in FEV(1) (PD20) given as the initial challenge was 54 .77 +/- 21.60 breath units, compared with 46.94 +/- 19.55 breath units when MIC followed EVH (p = 0.54). However, the subset of patients mos t sensitive to methacholine (PD20 < 0.1 breath unit) had changes sugge stive of a refractory period after EVH, with a mean increase in the PD 20 from 0.06 +/- 0.01 to 3.35 +/- 1.43 (p = 0.069). Our data show that MIC attenuates the response to subsequent challenge with EVH. Convers ely, EVH may only affect subsequent MIC in those most sensitive to met hacholine.