Aerosol furosemide for dyspnea: Controlled delivery does not improve effectiveness

•We tested hypotheses that might explain failure of aerosol furosemide to alleviate experimental dyspnea.•Control of aerosol delivery did not increase the proportion of subjects who responded.•Response variation was partially explained by variation of response to large breaths.•Response variation was inversely correlated with efficiency of furosemide uptake into the blood. Aerosolized furosemide has been shown to relieve dyspnea; nevertheless, all published studies have shown great variability in response. This dyspnea relief is thought to result from the stimulation of slowly adapting pulmonary stretch receptors simulating larger tidal volume. We hypothesized that better control over aerosol administration would produce more consistent dyspnea relief; we used a clinical ventilator to control inspiratory flow and tidal volume. Twelve healthy volunteers inhaled furosemide (40mg) or placebo in a double blind, randomized, crossover study. Breathing Discomfort was induced by hypercapnia during constrained ventilation before and after treatment. Both treatments reduced breathing discomfort by 20% full scale. Effectiveness of aerosol furosemide treatment was weakly correlated with larger tidal volume. Response to inhaled furosemide was inversely correlated to furosemide blood level, suggesting that variation among subjects in the fate of deposited drug may determine effectiveness. We conclude that control of aerosol delivery conditions does not improve consistency of treatment effect; we cannot, however, rule out placebo effect.