The Effect of Aerosol Saline on Laboratory-Induced Dyspnea

Abstract

Purpose: In the 'placebo arm' of a recent study, we found that aerosol saline (sham treatment) produced substantial relief of laboratory-induced dyspnea (Breathing discomfort-BD) in nearly half the subjects. The sham intervention included a physiological change, and instructions to subjects could have produced expectation of dyspnea relief. In the present study, we attempted to discover whether the response to sham aerosol was driven by behavioral or physiological aspects of the intervention.

Methods: Dyspnea (air hunger) was evoked by constraining tidal volume during graded hypercapnia. We measured [Formula: see text] versus BD relationship before and after aerosol saline. To minimize subjects' expectations of dyspnea relief, participants were clearly instructed that we would only deliver saline aerosol. In Protocol 1, we delivered aerosol saline with a ventilator (mimicking our prior study); in Protocol 2, we delivered aerosol without a ventilator.

Results: Administration of aerosol saline had little effect on BD in this group of subjects with one exception: one subject experienced appreciable reduction in BD in Protocol 1. This treatment effect was less in Protocol 2. The two most likely explanations are (a) that procedures surrounding ventilator administration of aerosol produced a psychological placebo treatment effect even though the subject knew a drug was not given; (b) there were behavioral changes in breathing undetected by our measurements of respiratory flow and volume that altered the subjects comfort.

Conclusion: When the expectation of treatment effect is minimized, a significant reduction in dyspnea in response to saline placebo is uncommon but not impossible.

Keywords: Aerosol treatment; Dyspnea; Placebo; Symptom management.

Fig. 1

Individual results for Protocol 1. Plots depict all up-step data points, regression lines, and coefficients of determination (r²). Blue indicates pre-treatment values, red indicates post-treatment values. In Protocol 1, saline aerosol was delivered with a ventilator to control inspiratory flow and volume.

Fig. 2

Treatment effect of aerosol saline delivered by ventilator to 5 subjects (Protocol 1). Negative values represent relief of dyspnea by treatment. Maximum possible treatment effects range from +40 to −60. Subject AF 32 was excluded because of tachypnea during stimulus presentation.

Fig. 3

Treatment effect of aerosol saline inhaled by 4 subjects (Protocol 2). Negative values represent relief of dyspnea by treatment. Maximum possible treatment effects range from +40 to −60. Subject AF 32 was excluded because of tachypnea; Subject AF31 dropped out before this protocol.

Fig. 4

Individual results for Protocol 2. Plots depict all up-step data points, regression lines, and coefficients of determination (r²). Blue indicates pre-treatment values, red indicates post-treatment values. In Protocol 2, subjects inspired the saline aerosol having been instructed to take slow, deep breaths.