Purpose: Psychological stress shifts the immune system toward the production of T-helper (Th)-2-mediated cytokines and eosinophilia, increases the risks for both asthma and depression, and can precipitate asthma exacerbations. Th2-mediated inflammation is a characteristic of allergic asthma. We have shown that the levels of CD4+ Th2 cells in the peripheral blood of patients with asthma are associated with severity and/or control of the disease. To improve our understanding of the interactions between stress and asthma symptoms, we evaluated the effects of psychological comorbidity on Th2-mediated inflammation in patients with asthma. Methods: Sixty-six asthmatic patients were recruited from the University of Alberta Asthma Clinic after they gave informed consent. Stress-related effects on asthma and psychological morbidity were assessed using the Asthma Control Questionnaire, completed by the patients at recruitment. Venous blood was collected at recruitment and Th2-mediated immunity evaluated by flow cytometry, quantitative real-time reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Findings: Patients with stress-triggered asthma (n = 12) had higher percentage of CD4+ T cells (P = 0.006) and Th2 cells (CD4+CRTh2+ T cells; P = 0.002) in peripheral blood compared to patients with asthma who did not experience stress-related worsening of disease (n = 54). The same was true when we analyzed patients with any form of psychological comorbidity (n = 19) compared to those without psychological comorbidities (n = 47). These differences were evident among women, but not among men. Women with psychological comorbidity also required higher doses of inhaled and oral corticosteroids compared to those without psychological comorbidity. Implications: Asthma involving psychological morbidity associates with an elevated level of circulating Th2 cells and increased corticosteroid usage, and may be more prevalent in women. Larger-scale prospective studies are required for assessing whether these women constitute a new endotype of Th2-high asthma responsive to treatments aimed to improve psychological comorbidities.Keywords: CRTh2; Th2 cells; asthma; psychological morbidity; stress; women.

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