Before puberty, girls have a lower risk for incident asthma, rhinitis, and respiratory multimorbidity compared with boys, but these incidences become more balanced after puberty, according to study results published in BMJ Open Respiratory Research.

Researchers conducted this independent meta-analysis of longitudinal birth cohorts to investigate whether there is a sex-specific and puberty-related pattern in asthma and rhinitis incidence, both as single entities and as respiratory multimorbidities. Data analyzed were taken from harmonized questionnaire responses from 18,451 participants in 5 prospective observational European birth cohorts within the MeDALL (Mechanisms of the Development of Allergy) project.

The primary outcomes were incident asthma, rhinitis, and respiratory multimorbidity. Definitions of immunoglobulin E (IgE)-associated and non-IgE associated conditions were based on both questionnaire responses and participants having recorded positive or negative allergic sensitization status to birch pollen, cat, dog, or house dust mites measured as specific IgE in serum (positive status ≥0.7 kU/L IgE to ≥1 of the 4 measurements, and negative status <0.7 kU/L). For each outcome, proportional hazard models with sex-puberty interaction terms were used, and a one-stage individual participant data meta-analysis was conducted.

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Asthma incidence was lower among girls compared with boys at preschool and early school age, with percentages decreasing for both girls and boys over time. Before the onset of puberty, girls were at a considerably lower risk for incident asthma (hazard ratio [HR], 0.67; 95% CI, 0.61-0.74) compared with boys, but this difference was less distinct after the onset of puberty (girls vs boys; HR, 0.84; 95% CI, 0.64-1.10; P =.122). Although the findings were similar for IgE-associated asthma, a more pronounced shift towards female predominance after the onset of puberty was found for non–IgE-associated asthma (before puberty: HR, 0.74; 95% CI, 0.63-0.87 vs after puberty: HR, 1.23; 95% CI, 0.75-2.00).

Before the onset of puberty, girls were at a considerably lower risk for incident rhinitis (HR, 0.73; 95% CI, 0.69-0.78), but this difference was less distinct and almost sex balanced after the onset of puberty (HR, 0.90; 95% CI, 0.79-1.02; P =.005). Male predominance remained nearly identical before and after puberty for IgE-associated rhinitis, but non–IgE-associated rhinitis switched to female predominance after the onset of puberty (before puberty: HR, 0.88; 95% CI, 0.79-0.98 vs after puberty: HR, 1.20; 95% CI, 0.98-1.47).

The risk for incident respiratory multimorbidity among girls was considerably lower compared with boys (HR, 0.58; 95% CI, 0.51-0.66) before puberty onset, but this risk became sex balanced after the onset of puberty (HR, 0.84; 95% CI, 0.63-1.13; P =.02). These findings were similar for IgE-associated multimorbidity incidence, and more sex balanced for non–IgE-associated respiratory multimorbidity incidence (before puberty: HR, 0.66; 95% CI, 0.49-0.88 vs after puberty: HR, 0.96; 95% CI, 0.54-1.71).

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The study limitations included the fact that the European cohort studies may not be generalizable, a lack of follow-up information, high dropout rates, and an inability to restrain the definition of incidence to 1 year.

Nonetheless, the investigators concluded, “Our [individual participant data] meta-analyses showed an incidence ‘sex shift’ in chronic respiratory diseases from males to females after puberty onset, which may partly explain the previously and more commonly reported prevalence ‘sex shift.’ The observed sex shift, especially for non–IgE-related incidences of the diseases, suggests sex-specific and puberty-specific underlying mechanisms. Our results stress the importance of raising alertness among clinicians for incident cases of respiratory diseases in adolescent girls for effective detection and timely treatment.”


Hohmann C, Keller T, Gehring U, et al. Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL [published online September 13, 2019]. BMJ Open Respir Res. doi:10.1136/bmjresp-2019-000460