Dysregulation of the stress response in asthmatic children

Abstract

The stress system co‐ordinates the adaptive responses of the organism to stressors of any kind. Inappropriate responsiveness may account for increased susceptibility to a variety of disorders, including asthma. Accumulated evidence from animal models suggests that exogenously applied stress enhances airway reactivity and increases allergen‐induced airway inflammation. This is in agreement with the clinical observation that stressful life events increase the risk of a new asthma attack. Activation of the hypothalamic–pituitary–adrenal (HPA) axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Data from animal models suggest that inability to increase glucocorticoid production in response to stress is associated with increased airway inflammation with mechanical dysfunction of the lungs. Recently, a growing body of evidence shows that asthmatic subjects who are not treated with inhaled corticosteroids (ICS) are likely to have an attenuated activity and/or responsiveness of their HPA axis. In line with this concept, most asthmatic children demonstrate improved HPA axis responsiveness on conventional doses of ICS, as their airway inflammation subsides. Few patients may experience further deterioration of adrenal function, a phenomenon which may be genetically determined.

Community violence and childhood asthma prevalence in peripheral neighborhoods in Salvador, Bahia State, Brazil

“…In addition, communities with heavier exposure to violence have limited access to health services, thus contributing to the severity of the asthma symptoms 12 . The literature further suggests that stress acts as a mediator between community violence and asthma symptoms 17,18,19 , but the fact that this variable was not the object of the current study highlights the importance of conducting longitudinal studies on the more precise relationship between these phenomena.…”

“…Findings suggest that families living in more violent communities keep their children longer at home, thus favoring contact with indoor allergens and triggering asthma attacks 10,12 . Evidence also shows that stress can directly trigger asthma symptoms 17,18,19 , becoming a mediator between community violence and asthma. It follows logically that violence in communities can aggravate asthma symptoms by reducing access to health services 12 .…”

Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study

“…54 Indeed, maternal exposure to cytokines during pregnancy was associated with adverse offspring outcome in rats, 55 and the association between maternal infection during pregnancy and offspring deficits appears to be mediated by cytokines, 56 even though the permeability of the placenta to cytokines remains unclear. 57,58 Third, the hypothalamicpituitary-adrenal (HPA) axis is another candidate mechanism linking maternal asthma during pregnancy with offspring diseases, as dysregulation of the HPA axis is a frequently observed feature of asthma 59 and changes in intrauterine glucocorticoid exposure have been shown to take effect in the fetus. 60 Fourth, one may speculate that asthma medication adversely affects the fetus.…”

Neuroimmunomodulation in Asthma: Focus on the Hypothalamic-Pituitary-Adrenal Axis

“…The resultant inadequate restraint of the immune and inflammatory response and airway reactivity increases the risk of asthma in subjects with the appropriate genetic predisposition [2] .…”

“…This decrease, combined with a reciprocal increase of the immune and inflammatory reaction -via known stress-immune system interactions -is supported by both experimental and clinical data. In addition to the effects of a restrained HPA axis on the allergic inflammatory reaction, the associated inappropriately decreased responsiveness of the stress system to stressors would be expected to also facilitate airway reactivity, therefore contributing to asthma manifestations [2] .…”