Psychological confounds in medical research: the example of excessive cough in asthma

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Abstract

This experiment tested the hypothesis that the setting in which research is conducted may dominate symptom magnitude. Cough was induced with inhaled citric acid and its magnitude was influenced by changing the setting in 30 adolescents with asthma. Cough thresholds for citric acid were determined. The participants were assigned to a condition emphasising asthma, or a control condition, described as estimation of lemon flavors. All participants inhaled (in different order) thresholds for citric acid, 50% of these thresholds, or placebo.

Results showed that both cough frequency and subjective ‘cough tendency’ were significantly higher in the asthma condition. State anxiety was higher in the asthma condition, but correlated only moderately with cough. Lung function, severity of asthma, trait anxiety, age or sex did not correlate with cough.

It was concluded that patients with asthma cough more often in a situation which they have learned to associate with asthma.

Introduction

The experience of noxious symptoms in medical settings is usually mechanistically conceptualized as a reflection of injury or pathophysiology. However, psychological and situational factors may confound results when symptoms as reported by patients themselves are used as dependent variables. Subtle differences between settings or interventions may systematically affect patients’ responses. Pennebaker and Skelton (1981) showed that the same ambiguous physical stimulus evoked painful or pleasurable symptoms, dependent on pre-experimental information to their subjects. Obviously, evoked activity in the sensory organs gives rise to perceptual processing, and activates stored memories to form the basis for the conscious experience of a symptom (Hendry, Hsiao & Brown, 1999). The perceptual process is influenced by meaning, relationships, context, judgment, and past experience (Schiffman, 1996). Pennebaker (1982) emphasized that a symptom is a subjective feeling state or experience, which often only loosely relates to objective, physical signs. A symptom can be a conviction or even a phantasy about the body, based on acquired knowledge. The magnitude of symptoms may also fluctuate with levels of perceived control over symptoms or distress (Pennebaker, 1982). For example, the presence of a friendly nurse may be decisive in symptom magnitude (Rietveld, Van Beest & Everaerd, 1999b). Although the influence of emotions in symptom magnitude is well established, few medical researchers measure them.

This experiment attempts to demonstrate the impact of situational factors (and patients’ reactions to them) on the cough response by patients with asthma.

Asthma is a chronic respiratory disease, characterized by episodic exacerbations of airway obstruction.

Cough is a prominent but ambiguous symptom in asthma. Whereas persistent cough may dominate asthmatic exacerbations, cough frequency does generally not linearly relate to parameters of asthma severity or lung function capacity (Boulet et al., 1994, Hsu et al., 1994, Rietveld and Rijssenbeek-Nouwens, 1998). Some patients do not cough during exacerbations of asthma, but others manifest cough as the only symptom of airway obstruction (Corrao et al., 1979, Hannaway and Hooper, 1982).

Reflex cough has a well-established somatic cause. Specific cough receptors and free C-fiber endings are sensitive to natural irritants (e.g. excessive mucus) or noxious gases and chemical substances (e.g. car fumes, hypertonic saline, carbagol or citric acid) (Fuller & Jackson, 1990). However, voluntary or conditioned cough may dominate a patient’s overall cough response (Eisenberg et al., 1997, Starkman and Appelblatt, 1984). Freestone and Eccles (1997) showed that the antitussive drug codeine was not more effective than placebo in reducing cough in patients with acute upper tract infection. They suggested the involvement of two central pathways for cough: (a) a reflex pathway via the brain stem which is sensitive to codeine, and (b) a voluntary pathway via the cortex which is sensitive to codeine as well as placebo. In another study, a remarkably high proportion of adolescents with asthma (54%) coughed immediately before a physical exercise task, whereas normal controls did not cough at all (Rietveld, Rijssenbeek-Nouwens & Prins, 1999a). The researchers speculated that the asthmatic adolescents coughed as a learned response to anticipated exercise-induced symptoms of asthma. Baseline cough in this study then would have been the result of anticipatory or conditioned responses to a situation associated with asthma (Rietveld & Prins, 1998b).

In summary, cough may be the symptom of choice for the current experiment because it has a well established somatic cause, and an important subjective component as well.

The hypothesis was that patients with asthma cough more often and report more subjective cough tendency when they are in an asthma-specific setting as compared to a non-asthmatic setting.

Section snippets

Participants

There were 30 adolescents with mild to severe stable asthma, aged 14 to 18 years (M=16.5, SD=1.6). They enrolled via family doctors in Amsterdam. Participants and parents were informed that there would be repeated inhalation of gases that could induce noxious sensations or cough. All signed informed consent. The participants were financially rewarded. The experiment was approved by the ethics committee of the Faculty of Psychology, following the norms of the American Psychological Association.

Results

One participant in the asthma condition and four participants in the control condition did not reach a cough threshold for citric acid and they were replaced. None of the participants developed airway obstruction during the experiment, as indicated by lung-function tests (Table 2).

The mean threshold for citric acid in the asthma condition was M=15.5% (SD=9.7) and in the control condition M=21.3% (SD=9.4). The difference in threshold between conditions was not significant, t(28)=−1.69, p=0.103

Discussion

This experiment showed that asthmatics coughed more frequently and reported more subjective cough tendency in the asthma condition as compared to the control condition. The experimental circumstances obviously were important for cough responses. Cough seemed clearly enhanced by a situation associated with asthma. Importantly, participants in the asthma condition seemed to discriminate less well in their cough responses to citric acid as compared to placebo. This lack of stimulus differentiation

Acknowledgements

The authors are grateful to Cedric Sands for proof-reading of the manuscript.

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