© 2005 American Thoracic Society doi: 10.1164/rccm.2503005
Asthma and PanicScope for Intervention?Department of General Practice and Primary Care, University of Aberdeen, Institute of Community Health Sciences, Queen Mary's School of Medicine and Dentistry, Aberdeen, United Kingdom In the 19th and early 20th centuries, asthma was viewed as a neurogenic disease in which imbalances in the nervous system and emotional factors played a fundamental role. Osler (1) referred to asthma as "a neurotic affection," and within living memory, relaxation techniques were widely advocated. Greater understanding of the inflammatory basis of asthma has rightly led to an emphasis on pharmacotherapy, yet despite undoubted progress, outcomes remain suboptimal (2), and many continue to suffer symptoms and impaired quality of life. Although few would now agree entirely with Osler, data continue to emerge supporting a link between asthma, emotion, and psychosocial factors. For instance, chronic stress and adverse life events appear to trigger exacerbations in children with asthma (3), and asthma-related health status is independently correlated with anxiety and depression scores (4). There is growing interest in the interface between stress, anxiety, and asthma (5). Cross-sectional studies show comorbidity between anxiety and asthma to be common; the prevalence of anxiety disorders is above expected in individuals with asthma, and conversely, asthma is more common in people with psychiatric illness. The relationship appears strongest in those with severe asthma and in those with severe anxiety. Speculation as to causality, mechanisms, and direction of relationship are hampered by the cross-sectional observational nature of previous data. This issue of the Journal (pp. 1224–1230) contains an important article from Hasler and colleagues (6), investigating the longitudinal relationship between asthma and panic in a prospective Swiss community-based cohort study. The authors investigated whether active asthma predicted subsequent panic disorders and explored whether panic predicted active asthma. Over 20 years, almost 600 subjects aged 19 years at enrollment underwent diagnostic interviews. The sample was enriched to include those at high risk of psychiatric disorder. Over 90% of subjects completed at least two interviews and almost half completed all six, allowing longitudinal relationships to be investigated. Although validated psychologic instruments were used, a weakness of the study is that asthma was assessed by the subjects reporting that they carried a diagnosis of asthma that had been made by a physician, and also had "asthmalike breathing problems" during the preceding 12 months, with active asthma defined as a diagnosis plus symptoms. The investigators found that, after adjusting for potential confounders, active asthma predicted subsequent panic disorder and panic disorder subsequent active asthma, this effect being stronger in women and in subjects younger than 30 years. The findings that asthma is associated with subsequent panic and panic disorder in people at risk of psychiatric morbidity and that panic disorder may be associated with subsequent worsening of asthma are highly plausible, but how sound are these observations? A possible confounder is the lack of objective confirmation of asthma. The lack of a simple gold-standard diagnostic test for asthma creates problems for community surveys, and "active asthma" here relies on subject self-reports of a physician diagnosis and memories of asthmalike symptoms in the previous year. Although diagnostic criteria are now clearly defined, we do not know how secure were the asthma diagnoses made by Swiss physicians over the study period (1978–1999). Similarly, "asthmalike symptoms" are nonspecific, and may overlap with the symptoms of panic and hyperventilation (7), raising the possibility of misattribution of respiratory symptoms arising from panic to asthma. The strength of the observed associations makes it unlikely, though not impossible, that this explains the relationships. If secure, the data imply that panic disorder may be implicated in exacerbations among those with asthma, and that symptomatic asthma may result in panic in susceptible individuals. Because of the lack of objective measurements, we do not know whether panic is affecting the severity of asthma, either directly or indirectly through effects on patients' behavior, or is subjectively affecting the way in which symptoms are perceived. What mechanisms might be involved? Emotion and stress may affect immune function in ill-understood ways (8). Panic may alter the behavior of individuals with asthma, leading to, for example, overuse of potentially anxiogenic asthma medication (9) and lack of compliance with preventative and self-management strategies. Hyperventilation is a common feature of panic, and may result in bronchospasm from cooling and drying of the airways by similar mechanisms to those occurring in exercise-induced bronchoconstriction. Furthermore, repeated hyperventilation has been shown in animal models to lead to inflamed and hyperreactive airways (10). Anxiety and panic may also potentially alter perception of respiratory symptoms in the absence of changes in objective asthma parameters. Patients vary in their perception of bronchoconstriction. In cross-sectional surveys, asthma symptoms correlate poorly with lung function (11), although independent correlations do exist between asthma-related health status and anxiety and depression scores (4). Functional brain imaging has indicated that the intensity of sensations of respiratory discomfort produced by loaded breathing may be modulated by parts of the brain associated with emotional processing (12). Could treatment of comorbid anxiety prevent asthma morbidity? A Cochrane review of psychotherapeutic interventions for adults with asthma found conflicting evidence (13), with some positive studies, but insufficient data to draw firm conclusions. There is some evidence of a role for breathing exercises in the treatment of asthma complicated by abnormal breathing patterns (14, 15). Panic is associated with respiratory symptoms and with abnormal breathing (hyperventilation, abnormal respiratory rate and effort), and respiratory control has been used as a treatment for panic attacks. Symptom patterns characteristic of dysfunctional breathing affect a significant minority of patients treated for asthma in the community (16), and breathing retraining programs improve asthma-related health status (15), symptoms, and bronchodilator use (14). The relationship of breathing modification to objective parameters of anxiety and asthma awaits clarification. The study by Hasler and colleagues (6) provides evidence of temporal relationships between panic and respiratory symptoms, and has important implications for practice and research. First, it emphasizes the need for diagnostic accuracy—in particular, the differentiation of asthma from symptomatic dysfunctional breathing associated with anxiety. Second, studies should test whether treatment of comorbid panic disorder reduces asthma morbidity. Third, the relationship between physiologic and psychologic factors in asthma needs urgent attention. This area presents methodologic challenges, but the increasing availability of validated tools and biomarkers assessing control, airways hyperreactivity, and inflammation should allow future observational and intervention studies to improve our understanding and effectiveness in this important area. FOOTNOTES Conflict of Interest Statement: M.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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