Sex-based hormonal influences on asthma biomarkers.

Abstract

Asthma, a chronic inflammatory airway disease affecting 25 million people in the United States, exhibits distinct sex differences in prevalence, phenotype, and treatment response. While asthma is more common in boys during childhood, adult women experience greater disease severity, likely due to hormonal and immunologic influences. Asthma biomarkers, including blood eosinophil count, fractional exhaled nitric oxide, IgE, and emerging markers, provide insight into disease phenotypes and therapeutic response. This review synthesizes current evidence on sex-specific differences in asthma biomarkers and mechanisms underlying these variations. Sex hormones play a role in immune modulation, with estrogen and progesterone promoting type 2 inflammation, and testosterone exerting suppressive effects. Boys demonstrate higher levels of blood eosinophil counts, fractional exhaled nitric oxide, total and allergen-specific IgE, and periostin, whereas postpubertal women exhibit increased IL-5, leptin, serum amyloid A, and urinary leukotriene E₄, along with lower adiponectin levels. In contrast, postpubertal male subjects with asthma show higher ceramide concentrations. Additional biomarkers under investigation include microRNAs, neutrophils, tryptase, exhaled breath condensate analytes, and surfactant proteins. However, evidence supporting these research-based markers is often preclinical and/or lacks sex-stratified analyses, limiting clinical translation. Incorporating validated sex-specific biomarker patterns into asthma care may enhance phenotyping and support personalized management strategies.