C R O'Donnell1,2, R W Lansing1, R M Schwartzstein1,2, Robert Banzett3,4. 1. Division of Pulmonary, Critical Care & Sleep Medicine, Beth Israel Deaconess Medical Center, Rm KB26, Boston, MA, 02215, USA. 2. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. 3. Division of Pulmonary, Critical Care & Sleep Medicine, Beth Israel Deaconess Medical Center, Rm KB26, Boston, MA, 02215, USA. rbanzett@bidmc.harvard.edu. 4. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA. rbanzett@bidmc.harvard.edu.
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.
RCT Entities:
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.
Authors: Robert B Banzett; Lewis Adams; Carl R O'Donnell; Sean A Gilman; Robert W Lansing; Richard M Schwartzstein Journal: Am J Respir Crit Care Med Date: 2011-07-21 Impact factor: 21.405
Authors: Robert B Banzett; Carl R O'Donnell; Tegan E Guilfoyle; Mark B Parshall; Richard M Schwartzstein; Paula M Meek; Richard H Gracely; Robert W Lansing Journal: Eur Respir J Date: 2015-03-18 Impact factor: 16.671
Authors: Robert B Banzett; Richard M Schwartzstein; Robert W Lansing; Carl R O'Donnell Journal: Respir Physiol Neurobiol Date: 2017-08-24 Impact factor: 1.931
Authors: Robert W Hallowell; Richard Schwartzstein; Carl R O'Donnell; Andrew Sheridan; Robert B Banzett Journal: Lung Date: 2019-11-15 Impact factor: 2.584
Authors: Marcus Waskiw-Ford; Anne Wu; Amar Mainra; Noah Marchand; Abdullatif Alhuzaim; Jean Bourbeau; Benjamin M Smith; Dennis Jensen Journal: Front Physiol Date: 2018-02-12 Impact factor: 4.566