Sex differences in childhood atopic disease and the role of sex-steroid metabolites

BACKGROUND: Studies have described sex differences in childhood asthma, allergy, and atopic dermatitis, but the development and clinical phenotype of these differences remain poorly understood.

OBJECTIVE: To characterize sex differences in atopic disease throughout childhood and study the potential role of sex-steroid metabolites.

METHODS: We examined sex differences in asthma, allergy, and atopic dermatitis using longitudinal generalized estimating equation models in the COPSAC2000 (n=411) and COPSAC2010 (n=700) birth cohorts. We further examined possible mechanisms through early-life sex-steroid metabolites.

RESULTS: In combined analyses of COPSAC2000 and COPSAC2010 until age 6 years, males had a higher prevalence of asthma compared to females (25% vs 20%): OR=1.48 (95% CI, 1.09-2.02) and experienced more asthma exacerbations: IRR=1.87 (1.37-2.55). Males had a higher prevalence of allergic sensitization (37% vs 31%): OR=1.54 (1.20-1.98), and higher blood eosinophil count: GMR=1.16 (1.07-1.27), which may indicate Type 2-inflammation. These sex differences persisted until age 18 years in COPSAC2000, except for asthma prevalence, whereas males had a higher prevalence of allergic rhinitis and a higher fraction of exhaled nitric oxide. During preschool-age, five of the measured sex-steroid metabolites significantly mediated parts of the sex differences in allergic sensitization (range of proportion mediated: 0.16-0.18) and/or blood eosinophils (range of proportion mediated: 0.22-0.25).

CONCLUSION: Males had a higher prevalence of asthma, more frequent asthma exacerbations, higher prevalence of allergic sensitization, and higher blood eosinophil count than females during early childhood across two birth cohorts. These sex differences, which may indicate Type 2-inflammation, persisted into adolescence and were partly explained by sex-steroid metabolites.