Comparison of Responses to Methacholine and Cold Air in Patients Suspected of Having Asthma: Episode of hyperventilation
For practical reasons, we usually did both cold and methacholine challenges on the same day, the cold air being first. Only when cold-air hyperventilation produced substantial symptomatic bronchoconstriction was the subsequent methacholine challenge done on another day. This raises the question of whether the cold-air challenge influenced the results of the methacholine test. There are contradictory data in the literature regarding the presence of a refractory period after cold-air hyperventilation. Some authors found that successive same-day cold-air challenges are reproducible in asthmatic patients, while others found that this is not the case, the second response being smaller than the first, and they postulated that this is due to relative failure of mediator release with the second challenge.
There is much evidence, however, that bronchoconstriction after cold-air hyperventilation is not due to release of mediators. Further, methacholine-induced bronchoconstriction is not thought to be due to endogenous mediators. Finally, studies showing refractoriness after cold air challenge have all used repeated cold-air exposure as the second stimulus. The one study we are aware of that studied responses to methacholine before and after cold-air testing found that they were unaffected. Thus, we believe that it is unlikely that the methacholine responses we observed were altered by the previous cold air exposure. Link
Our cold-air challenge consisted of a single episode of hyperventilation conducted at the highest level of ventilation that the patient could attain. Although one previous study compared this kind of test with methacholine challenge and found close correspondence between the two, most comparative experiments have constructed cold-air dose-response curves by having subjects maintain successively higher levels of ventilation and measuring changes in FEV! after each. This approach yields data directly comparable to those resulting from the usual methacholine challenge, and is in some ways preferable to the method we used. However, acquisition of data for cold-air dose-response curves is cumbersome, time consuming, and not well suited to clinical routine, and we were interested in comparing results of the tests as they are utilized in clinical practice.