Introduction

Sex differences in childhood asthma, allergy, and atopic dermatitis have previously been described, but the development, clinical phenotype, and nature of these sex differences is not well understood. Therefore, we investigated sex differences in these diseases and explored possible underlying mechanisms.  

Methods

This study was conducted in the COPSAC2000 (n=411) and COPSAC2010 (n=700) prospective mother-child cohorts. We examined sex differences in the prevalence of asthma, allergy, and atopic dermatitis outcomes using longitudinal generalized estimating equation models. In COPSAC2010 we examined if the airway immune profile, systemic inflammation, functional stimulated immune responses or sex hormone metabolites (androgens, pregnenolones, and progestins) mediated the observed sex differences.

Results

In both cohorts, boys had a higher prevalence of asthma: OR=1.41 (95% CI, 1.00-1.97) and 1.7 (1.01-2.86), especially T2-high asthma, higher prevalence of allergic sensitisation: 1.69 (1.20-2.39) and 1.58 (0.98-2.55), and more exacerbations: IRR=1.79 (1.18-2.27) and 1.92 (1.24-2.97) until 6 years. Furthermore, boys had higher blood eosinophils and airway resistance (sRaw). Sex hormone metabolite levels in blood measured at 18 months and 6 years mediated parts of the sex differences in allergic sensitisation and blood eosinophils.

Conclusion

Boys had higher prevalence of asthma and allergy outcomes, more asthma exacerbations, and poorer lung function compared to girls through childhood. This sex divergence was mostly driven by a T2 inflammatory phenotype and was partly mediated through differences in levels of sex hormone metabolites in early childhood.