Pathophysiology of dyspnea evaluated by breath-holding test: studies of furosemide treatment.

Breath-holding is one of the most powerful methods to induce the dyspneic sensation, and the breath-holding test gives us much information on the onset and endurance of dyspnea. In conscious subjects, immediately after the start of breath-holding at functional residual capacity (FRC), there is a certain period of no particular respiratory sensation lasting for 20-30s, which is designated "no respiratory sensation period". This period is terminated by the onset of dyspnea and followed by a progressive increase in the intensity of dyspnea until the breaking point of breath-holding. The measurement of the period of no respiratory sensation provides us with information about the threshold of dyspneic sensation whereas the measurement of the total breath-holding time is a behavioral measure of the tolerable limit of dyspneic sensation. The behavioral measure of tolerable limit of dyspnea can permit the study of dyspnea even in anesthetized animals while observing escape behavior in response to airway occlusion. Inhaled furosemide causes prolongation of both the period of no respiratory sensation and total breath-holding time in conscious subjects, indicating that inhaled furosemide alleviates experimentally induced dyspnea. Alleviation of dyspnea with inhaled furosemide in conscious subjects is also consistent with the result of animal studies in which inhaled furosemide suppresses the escape behavior in the lightly anesthetized condition. The purpose of this article is to emphasize the usefulness of breath-holding test as a tool for evaluation of dyspnea. Furthermore, the possible mechanisms of alleviation of dyspnea with inhaled furosemide are highlighted.