Fig. 1

Sex differences in airway disease. A In cystic fibrosis, women have worse lung function exacerbations and higher mortality than men. Estrogen has aggravating effects on airway surface liquid dynamics in CF to reduce mucociliary clearance, increase mucus secretion and promote bacterial invasion and virulence. B In asthma, boys have worse lung exacerbations than girls pre-puberty, whereas women have more frequent and aggravated asthma episodes than men post-puberty. During pre-puberty, boys have dysanaptic lung development (larger and more hyperactive airways). During post-puberty, estrogen dehydrates the airway surface liquid and promotes mucus plugging of the airways and is hyper-allergenic whereas testosterone is hypo-allergenic. C In COVID-19, women have less severe morbidity and mortality than men. Sex steroids may account for this female advantage through several mechanism; X-linked genes offer enhanced immuno-protection and estrogen causes the suppression of ACE2-R expression. Together these responses reduce SARS-Cov-2 cellular invasion, inhibit inflammatory cytokines, activate the protective vasodilatory arm of RAS, and inhibit airway secretions to lower ASL height (ASLh) and reduce airway flooding. Testosterone, on the other hand, increases ACE2-R expression and is immuno-suppressant