Sex discordance in asthma and wheeze prevalence in two longitudinal cohorts

Abstract

Sex discordance in asthma prevalence has been previously reported, with higher prevalence in males before puberty, and in females after puberty; the adolescent "switch". However, cross-sectional studies have suggested a narrowing of this discordance in recent decades. We used a combination of cross-sectional and longitudinal modelling to examine sex differences in asthma, wheeze and longitudinal wheezing phenotypes in two UK birth cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC; born 1991-92 with data from age 0-18 years) and the Millennium Cohort Study (MCS; born 2000-02 with data from age 3-10 years). We derived measures of asthma and wheeze from questionnaires completed by mothers and cohort children. Previously-derived ALSPAC wheezing phenotype models were applied to MCS. Males had a higher prevalence of asthma at 10.7 years in ALSPAC (OR 1.45 95%CI: 1.26, 1.66 n = 7778 for current asthma) and MCS (OR 1.42 95%CI: 1.29, 1.56 n = 6726 for asthma ever) compared to females, decreasing in ALSPAC after puberty (OR 0.94 95%CI: 0.79, 1.11 n = 5023 for current asthma at 16.5 years). In longitudinal models using restricted cubic splines, males had a clear excess for asthma in the last 12 months and wheeze in the last 12 months up until 16.5 years of age in ALSPAC. Males had an increased risk of all derived longitudinal wheezing phenotypes in MCS when compared to never wheeze and no evidence of being at lower risk of late wheeze when compared to early wheeze. By comparing data in two large, contemporary cohorts we have shown the persistence of sex discordance in childhood asthma, with no evidence that the sex discordance is narrowing in recent cohorts.

Fig 1. Concepts of (A) confounding and (B) mediation in epidemiological studies illustrated using a Directed acyclic graph (DAG).

In the case of sex and asthma, where sex is the exposure and asthma status the outcome, any extraneous factors must go by the mediation pathway, as nothing can influence a child’s sex at conception.

Fig 2. Male odds ratios for wheeze in the last 12 months and asthma in the last 12 months, in ALSPAC.

Fig 3. Male odds ratios for ever wheeze, ever asthma and wheeze in the last 12 months in the MCS at 4 time-points.

Fig 4. Estimated prevalence of wheezing at each time-point from 3.1 to 10.7 years for each of the four wheezing phenotypes identified by latent class analysis in 7349 participants with complete observations of wheeze in the last 12 months in the MCS.

Fig 5. Longitudinal logistic models using cubic splines of repeated wheeze and asthma measures by sex.

Males are in blue and females in red. Shaded areas represent 95% confidence intervals. Measures of (A) asthma in the last 12 months in ALSPAC (B) wheeze in the last 12 months in ALSPAC (C) asthma ever in the MCS (D) wheeze in the last 12 months in the MCS and (E) wheeze ever in the MCS.