Sex and gender in interstitial lung diseases

Abstract

Sex and gender differences influence key domains of research, lung health, healthcare access and healthcare delivery. In interstitial lung diseases (ILDs), mouse models of pulmonary fibrosis are clearly influenced by sex hormones. Additionally, short telomeres, a biomarker of telomere regulation gene mutations, are impacted by sex, while heritability unexplained by genetic variation may be attributable to gendered environmental factors that drive epigenetic control. Diseases like idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, occupational ILDs, connective tissue-associated ILDs and lymphangioleiomyomatosis have different prevalence and prognosis between men and women. These differences arise from a complex interplay between biological sex and sociocultural gender influencing genetics, epigenomic modifiers, hormones, immune function, response to treatment and interaction with healthcare systems. Much work remains to be done to systematically integrate sex and gender analysis into relevant domains of science and clinical care in ILD, from strategic considerations for establishing research priorities to guidelines for establishing best clinical practices. Accounting for sex and gender in ILD is essential to the practice of individualised, patient-centred medicine.

FIGURE 1

Complex interplay of sex and gender influencing health outcomes. a) Animal models of pulmonary fibrosis are exclusively performed in male mice; b) genetic and epigenetic determinants of sex and/or gender differences in interstitial lung diseases (ILDs); c) environmental and occupational exposures are highly gendered; d) healthcare utilisation and access are gendered and impact outcomes; e) sex and gender needs to be incorporated in the ILD fellowship training towards a more patient-centred medicine; f) clinical research needs to be stratified on sex/gender in order to avoid missing possible gender/sex effect modification on outcomes.