Asthma diagnosis and treatment
Placebo response in asthma: A robust and objective phenomenon

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Background

Placebos are hypothesized to exert positive effects on medical conditions by enhancing patient expectancies. Recent reviews suggest that placebo benefits are restricted to subjective responses, like pain, but might be ineffective for objective physiologic outcomes. Nevertheless, mind-body links and placebo responsivity in asthma are widely believed to exist.

Objective

We carried out a randomized, double-blind investigation to (1) determine whether placebo can suppress airway hyperreactivity in asthmatic subjects, (2) quantify the placebo effect, (3) identify predictors of the placebo response, and (4) determine whether physician interventions modify the placebo response.

Methods

In a double-blind, crossover design investigation, 55 subjects with mild intermittent and persistent asthma with stable airway hyperreactivity were randomized to placebo or salmeterol before serial methacholine challenges. Subjects were additionally randomized to physician interactions that communicated either positive or neutral expectancies regarding drug effect.

Results

Placebo bronchodilator administration significantly reduced bronchial hyperreactivity compared with baseline (the calculated concentration of methacholine required to induce a 20% decrease in FEV1 nearly doubled); 18% of subjects were placebo responders by using conservative definitions. Experimental manipulation of physician behavior altered perceptions of the physician but not the magnitude or frequency of the placebo response.

Conclusions

Objective placebo effects exist in asthma. These responses are of significant magnitude and likely to be meaningful clinically. The placebo response was not modulated by alterations in physician behavior in this study.

Clinical implications

The placebo response in patients with asthma is important in understanding the limitations of clinical research studies and in maximizing safe and effective therapies. This article confirms the existence of a strong placebo response in an objective and clinically relevant measure of disease activity.

Section snippets

Participants

Subjects were recruited at the National Jewish Medical and Research Center and the University of Iowa. Eligible subjects were men and women, aged 18 to 55 years, with mild intermittent or persistent asthma17 and a baseline FEV1 of 80% of predicted value or greater. Major exclusion criteria included pregnancy or breast-feeding, serious systemic illness, recent respiratory tract infection, use of inhaled corticosteroids or other controller medications within 4 weeks, and smoking (>5 pack-year

Participants

Fifty-five subjects completed the study at 2 sites. Five subjects dropped out after the second screening visit; none were disqualified because of unstable airway hyperresponsiveness. The mean age of participants was 29.7 years (SD, 11.3); women comprised 56.4% of the population, and 91% of the sample was white. Mean BMI was 30.2 (SD, 6.5). There were no significant differences between those assigned to the enhanced and the efficient physician conditions in any demographic, psychologic, or

Discussion

The last decade has seen an increased interest in the placebo response in physical disease, and placebo effects have been documented in numerous conditions.2 Recently, the neural circuitry underlying these effects has begun to be mapped.20 However, the vast majority of studies examine effects in subjectively experienced outcomes, such as pain and depression, suggesting higher-order brain modulation of central processes relevant to these conditions. Relatively little is known about the ability

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    Supported by the Mind, Body, Brain, and Health Initiative and the National Institutes of Health (RR020645, RR00059, and ES05605).

    Disclosure of potential conflict of interest: J. N. Kline has consulting arrangements with Critical Therapeutics and Genentech; has received grant support from the National Institutes of Health, Centocor, Genentech, GlaxoSmithKline, and Novartis; and is on the speakers' bureau for Merck, GlaxoSmithKline, Critical Therapeutics, and Genentech. R. A. Panettieri has consulting arrangements with AstraZeneca, AtheroGenics, BioMarck, BioWa, Centocor, Enhanced Pharmaceuticals, Epigenesis, GlaxoSmithKline, Johnson & Johnson, Merck, Sepracor, and Tanox; has received grant support from Centocor, Epigenesis, GlaxoSmithKline, Merck, Prolexys, Novartis, and Sepracor; and is on the speakers' bureau for AstraZeneca, GlaxoSmithKline, Merck, and Novartis. The rest of the authors have declared that they have no conflict of interest.

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