Active albuterol or placebo, sham acupuncture, or no intervention in asthma

Abstract

Background: In prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention. We compared the effects of a bronchodilator, two placebo interventions, and no intervention on outcomes in patients with asthma.

Methods: In a double-blind, crossover pilot study, we randomly assigned 46 patients with asthma to active treatment with an albuterol inhaler, a placebo inhaler, sham acupuncture, or no intervention. Using a block design, we administered one each of these four interventions in random order during four sequential visits (3 to 7 days apart); this procedure was repeated in two more blocks of visits (for a total of 12 visits by each patient). At each visit, spirometry was performed repeatedly over a period of 2 hours. Maximum forced expiratory volume in 1 second (FEV(1)) was measured, and patients' self-reported improvement ratings were recorded.

Results: Among the 39 patients who completed the study, albuterol resulted in a 20% increase in FEV(1), as compared with approximately 7% with each of the other three interventions (P<0.001). However, patients' reports of improvement after the intervention did not differ significantly for the albuterol inhaler (50% improvement), placebo inhaler (45%), or sham acupuncture (46%), but the subjective improvement with all three of these interventions was significantly greater than that with the no-intervention control (21%) (P<0.001).

Conclusions: Although albuterol, but not the two placebo interventions, improved FEV(1) in these patients with asthma, albuterol provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated responses in asthma may be essential in evaluating patient-reported outcomes. (Funded by the National Center for Complementary and Alternative Medicine.).

Figure 1. Schema for Study Interventions

The time between blocks varied, but was generally 3 to 7 days.

Figure 2. Screening and Randomization

Figure 3. Percent Change in Maximum Forced Expiratory Volume in 1 Second (FEV₁) with Each of the Four Interventions

The relative improvement in FEV₁ achieved with albuterol was significantly greater than that achieved with each of the other three interventions (P<0.001). No other differences among the four experimental conditions were significant. T bars indicate standard errors.

Figure 4. Percent Change in Subjective Improvement with Each of the Four Interventions

The relative improvement in subjective outcomes, assessed with the use of a visual-analogue scale (with 0 indicating no improvement and 10 indicating complete improvement), was significantly greater with the albuterol inhaler, placebo inhaler, and sham acupuncture interventions than with the no-intervention control (P<0.001). No other differences among the four experimental conditions were significant. T bars indicate standard errors.