Sex and gender in asthma

Abstract

Asthma is a heterogenous disease, and its prevalence and severity are different in males versus females through various ages. As children, boys have an increased prevalence of asthma. As adults, women have an increased prevalence and severity of asthma. Sex hormones, genetic and epigenetic variations, social and environmental factors, and responses to asthma therapeutics are important factors in the sex differences observed in asthma incidence, prevalence and severity. For women, fluctuations in sex hormone levels during puberty, the menstrual cycle and pregnancy are associated with asthma pathogenesis. Further, sex differences in gene expression and epigenetic modifications and responses to environmental factors, including SARS-CoV-2 infections, are associated with differences in asthma incidence, prevalence and symptoms. We review the role of sex hormones, genetics and epigenetics, and their interactions with the environment in the clinical manifestations and therapeutic response of asthma.

Gene‐environment interactions in childhood asthma revisited; expanding the interaction concept

“…Childhood‐onset asthma is more prevalent in prepubertal men although with a less severe phenotype, even though the lifetime risk of asthma is higher in women 83 . A complex network of different factors has been proposed to play an important role, 83 including genotype‐by‐sex interactions. For instance, two SNPs at the IFNG gene were associated with a decreased risk for the development of childhood asthma in women compared with men of the same age with a history of wheezing early in life 84 .…”

Blood inflammatory phenotypes were associated with distinct clinical expressions of asthma in adults from a large population-based cohort

“…As the prevalence of asthma differs between men and women, 24 and asthma and chronic obstructive pulmonary disease (COPD) have several symptoms in common, stratified analyses by sex or by age (<40 years and ≥ 40 years) were performed. For these analyses, tests of homogeneity were performed by fitting the interaction-term in the logistic model; to take into account multiple comparisons, the Bonferroni corrected significance p-value threshold was calculated (14 comparisons, threshold p value=0·05/14=0·004).…”

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

“…1 Currently available biologics are mostly targeted towards type 2 high inflammation, such as omalizumab (anti-IgE), dupilumab (anti-IL-4 receptor α ), mepolizumab (anti-IL-5) and benralizumab (anti-IL-5 receptor α ), which is generally less common in women than in men. 1 , 127 , 163 However, gender differences in the efficacy of the biologics in severe asthma have not been extensively investigated. 163 , 164 Some randomized trials explored gender differences in responsiveness to these biologics and did not find differential responses between women and men.…”

“…1 , 127 , 163 However, gender differences in the efficacy of the biologics in severe asthma have not been extensively investigated. 163 , 164 Some randomized trials explored gender differences in responsiveness to these biologics and did not find differential responses between women and men. 165–171 To our knowledge, no human studies have looked at the effects of these biologics on hormonal activity.…”