Invited MinireviewStress and inflammation in exacerbations of asthma
Introduction
Physicians, scientists, and laypeople have long believed that stress contributes to exacerbations of asthma. However, it has only been in the past two decades that convincing scientific evidence has accumulated to substantiate this hypothesis. For example, in an 18-month prospective study of children with asthma, the experience of an acute negative life event (e.g., death of a close family member) increased the risk of a subsequent asthma attack by nearly 2-fold (Sandberg et al., 2000). The impact of an acute negative event was accentuated when it occurred in the context of chronic stress. Children exposed to high levels of acute and chronic stress showed a 3-fold increase in risk for an attack in the 2 weeks that followed the acute event. Despite the recent empirical evidence linking stress with the clinical profile of asthma, much remains to be learned about the biological mechanisms underlying this phenomenon. In this mini-review, we outline a model highlighting inflammation as a central mediating pathway. It focuses on immunologic mechanisms that allow stress to “get inside the body” and exacerbate symptoms of patients with asthma. Because the role of stress in asthma onset has been thoughtfully discussed elsewhere (Wright, 2005, Wright et al., 2005), and probably involves different behavioral and biological mediators, we do not attempt to cover it here.
Section snippets
What is stress?
Stress has been defined in many ways in the scientific literature. One of the most common psychological definitions has been that stress occurs when demands from the environment challenge an individual’s adaptive capacity, or ability to cope (Cohen et al., 1995). Frequently termed “stressors”, these demands include negative life events such as job loss, death of a loved one, and family conflict. Within this conceptualization of stress, researchers have typically distinguished between acute and
How does stress affect asthma?
Fig. 1 depicts our working model of stress and asthma. It highlights the importance of both social and physical exposures in the exacerbation of symptoms. The basic premise of the model is that psychological stress operates by altering the magnitude of the airway inflammatory response that irritants, allergens, and infections bring about in persons with asthma. It is important to note that the model suggests that stress on its own is NOT capable of modifying immune functions in a way that leads
What’s the evidence for the model?
With the basic outline of the model sketched, we next describe a number of human studies that illustrate empirical approaches to assessing one or more aspects of this model.
How does stress modify inflammation?
Having provided support for the basic premises of our working model, we now turn to details of how stress amplifies the immune response to asthma triggers. Fig. 1 provides an overview of the relevant pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) axis, and the two major divisions of the autonomic nervous system, sympathetic (SNS) and parasympathetic (PNS).
What’s next?
We have used this mini-review to outline the premises of a working model of stress and asthma. Although a number of the model’s important predictions have been confirmed, more work needs to be done before its overall utility can be evaluated. Next steps for future research should include addressing questions such as: do stressful experiences foster asthmatic symptoms by accentuating inflammatory responses to allergic, infectious, and chemical triggers? To what degree are diminished sensitivity
Acknowledgment
This article was supported by NIH Grant HL073975.
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