Elevated Circulating Th2 Cells in Women With Asthma and Psychological Morbidity: A New Asthma Endotype?

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.

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.

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.

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.