Imbalance of endogenous prostanoids in moderate-to-severe asthma

Background: Inhalation studies suggested "protective" roles of exogenous prostaglandin E-2, but the clinical relevance of endogenous prostanoids in asthma is poorly known. The objective of this study is to measure sputum levels of prostanoids in asthmatic patients to correlate with clinical indices. Methods: Mild (n = 41) or moderate-to-severe (19) asthmatics and 27 normal controls were examined for pulmonary function (FEV1 and mid-forced expiratory flow), sputum cell differentials, and sputum levels of prostaglandins D-2, E-2, F-2 alpha, and thromboxane B-2 measured by sandwich enzyme immunoassay. Results: Each prostanoid level did not differ among the three groups. Sputum number of bronchial epithelial cells was greater in moderate-to-severe asthmatics than in the other two groups, suggesting epithelial desquamation. Levels of prostaglandin F-2 alpha, D-2, and thromboxane B-2 positively correlated with the severity of airflow obstruction in the 60 asthmatic patients, whereas prostaglandin E-2 levels were unrelated to pulmonary function. The ratio of combined "contractile" prostanoids (prostaglandin D-2/prostaglandin F-2 alpha/thromboxane B-2) to prostaglandin E-2 was 2.5-fold greater in moderate-to-severe asthmatics than in controls (p = 0.001) or in mild asthmatics (p = 0.0002) but did not differ between the latter two groups. In the two asthmatic groups combined, this ratio positively correlated with the sputum number of epithelial cells. The combined "contractile" prostanoids levels positively correlated with prostaglandin E-2 levels in controls and in mild asthmatics but not in moderate-to-severe asthmatics. Conclusions: An imbalance in production, breakdown, or both between prostaglandin E-2 and other prostanoids possibly due to epithelial damage may be involved in the pathogenesis of moderate-to severe asthma. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.