The failure to observe a fall in ventilation after methacholine challenge is not likely to result from our use of the Respitrace, since this device tended to underestimate the tidal volume changes following induced bronchoconstriction. It thus seems likely that much of the hypoxemia resulted from changes in the distribution of alveolar ventilation to perfusion ratios within lung alveoli following bronchoconstriction.

There are conflicting results on the effect of bronchoconstriction on breathing patterns. Minute ventilation has been found to increase to be unchanged or decreased with respiratory frequency either increasing or unchanged. Some of these differences may be due to the use of mouthpieces in many studies which may alter breathing patterns. Differing severities of bronchoconstriction may also be important, as the effect of moderate and severe bronchoconstriction on breathing pattern may be different. Further, some of these studies were on normal subjects and some on patients with chronic bronchitis and emphysema, and these groups may respond differently to bronchoconstriction. The only directly comparable study is that of Tobin et al, who studied breathing pattern using an inductive technique following methacholine-induced bronchoconstriction in asthmatic patients and found no change in the breathing pattern, which agrees with our result with methacholine but not when a similar degree of bronchoconstriction was induced by histamine inhalation.

The extent of the fall of FEV! induced by histamine (37 ±11 percent) and by methacholine (34 ±11 percent) was similar, and there were also similar falls in oxygen saturation with both agents. The changes in timing were significant following histamine challenge but not following methacholine challenge. This is compatible with the agents’ having different types of actions, histamine perhaps stimulating airway affer-ents, which modulate breathing pattern.
Bronchial challenge can produce hypoxia in stable asthmatic patients. This may result from a combination of hypoventilation with alterations in alveolar ventilation/perfusion relationships following bronchocon-striction.