Sex Differences in Asthma Pathogenesis

There is a sex difference in asthma prevalence and asthma-related morbidity that changes from childhood into different reproductive stages of life. The impact of sex hormone signaling on asthma pathogenesis has been partially elucidated using large cohort human studies, human cells, and animal models. Androgens decreased airway inflammation by reducing type 2 inflammation and eosinophil infiltration as well as reducing neutrophil-induced airway inflammation in animal models. Estrogen signaling through ER-α increased IL-33 production, an alarmin produced by airway epithelial cells that increases type 2 inflammation and increased Th17 cell-mediated neutrophilic inflammation. Additional studies are needed to determine what happens to asthma control and asthma-induced inflammation in women during pregnancy and menopause as well as how sex differences in immune cell development and airway inflammation affect asthma incidence and onset during childhood. Collectively, understanding that sex differences in asthma risk and control exist throughout life is important to personalize therapies for males and females with asthma.