Furosemide is known to influence the activity of vagally mediated mechanoreceptors in the airways. Because vagal afferent fibers may play an important role in modulation of the sensation of dyspnea, it is possible that inhaled furosemide may modify the sensation of dyspnea. In a double-blind, randomized, crossover study, we compared the effect of inhaled furosemide on dyspneic sensation with that of placebo. Severe dyspneic sensation was induced in 12 healthy subjects in two ways: (1) breathholding and (2) loaded breathing with a combination of inspiratory resistive load (240 cm H(2)O/L/s) and hypercapnia induced by extra mechanical dead space (0.26 L). Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale (dyspneic VAS). Breathholding times and changes in dyspneic VAS score during a 5-min period of loaded breathing were measured after inhalation of placebo and furosemide (40 mg). Total breathholding time after inhalation of furosemide (median, 93 [interquartile range, 78 to 112]s) was prolonged compared with the total breathholding time after placebo inhalation (67 [47-74]s). We also found that respiratory discomfort during loaded breathing after inhalation of furosemide develops more slowly and is less than that observed after inhalation of placebo. Our findings indicate that inhaled furosemide greatly alleviates the sensation of dyspnea induced experimentally by breathholding and by a combination of resistive loading and hypercapnia.