• Theoharis C Theoharides, Souad Enakuaa, Nikolaos Sismanopoulos, Shahrzad Asadi, Evangelos C Papadimas, Asimenia Angelidou, and Konstantinos-Dionysios Alysandratos.
• Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Tufts Medical Center, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
• Ann. Allergy Asthma Immunol. 2012 Jul 1; 109 (1): 14-9.

ObjectiveTo review the available evidence linking stress to asthma and to investigate whether mast cells contribute to the effect of stress through activation by corticotropin-releasing hormone (CRH).Data SourceThe PubMed database was searched for articles (1998-2011) using the keywords anxiety, asthma, exacerbation, inflammation, mast cells, socioeconomic status, stress, violence, and worsening.Study SelectionArticles were selected based on their relevance to the topic, with emphasis on clinical or epidemiologic data linking stress to asthma and studies that offered possible explanations for how stress may affect asthma.ResultsMany articles point to an association between stress (socioeconomic status, interpersonal conflicts, emotional distress, terrorism) and asthma exacerbations but without any distinct pathogenetic mechanism. A few articles have reported reduced circulating cortisol and/or sensitivity to corticosteroids. We propose that mast cells, known to be involved in the pathophysiology of asthma, can be activated by CRH, which is secreted under stress in the lungs, leading to selective release of proinflammatory mediators. This effect may be augmented by neuropeptides or cytokines. CRH also reduces T-regulatory cell production of interleukin 10, which in known to inhibit allergic mast cell activation.ConclusionMore studies are required to investigate lung levels of CRH and selective mast cell mediators. Reducing stress and using CRH receptor antagonists and/or mast cell blockers may serve as possible new therapeutic approaches for asthma.Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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