Sex and Gender in Asthma, COPD, OSA, ILD, and Lung Cancer

A literature review recently published in Chest discusses the specific effects of sex and gender on the epidemiology, presentation, risk factors and management of lung diseases. “Understanding these differences is the first step in moving towards precision medicine for women,” said review authors, who described their work as a “state-of-the-art review.”

According to review authors, sex and gender differences as they relate to respiratory diseases and sleep disorders have only been explored in detail during the last decade and a dearth in research still exists on this topic. To investigate this phenomenon, review authors searched PubMed from 1980 to present, using the search terms “lung and (sex or gender),” documenting the number of studies found and showing the increase in the number of studies meeting these search parameters over time. The reviewers compared the results of their “lung and (sex or gender)” search to those of a similar search based on the terms “heart and (sex or gender),” finding over twice as many studies relating to the “heart” vs “lung” search.

Reviewers also compiled statistics on the prevalence of airway diseases (ie, COPD and asthma), lung cancer, and interstitial lung disease (ILD) by sex. These statistics showed that COPD rates in females are almost as high as those in males (7.3 % vs 8.07%, respectively), that rates of adult asthma are much higher in females than males (9.8% vs 6.3%, respectively), that although lung cancer rates in the US are higher in males (55.3%) than in females (44.2%), the rate of lung cancer among never-smokers is higher in females (15.2%) than in males (11.2%); and that among those with ILD, rates of fibrosing  and progressive fibrosing ILD are nearly similar in males and females.

A key point of the review related to the differences between “sex” and “gender” and the importance of acknowledging this difference in future research. The authors provided definitions for “sex” and “gender”: “sex,” a biological construct, indicates biological status defined by a combination of anatomical features, genetics, sex organs, and hormones; whereas “gender,” a psychological and social construct, “reflects behaviors, attitudes, and feelings of a person in the context of their historical and cultural milieu,” and includes factors such as work roles, environmental exposures, societal roles, and social support, according to review authors.

In their discussion of review findings, the authors noted that: (1) Ample evidence shows that sex and gender affect the incidence, susceptibility, presentation, diagnosis, and severity of many lung diseases, and it is also notable that certain respiratory diseases and occurrences are unique to women/females. (2) Sex and reproductive transitions affect various aspects of lung/sleep biology and pathobiology, and differential gene expression or organ development can also be impacted by these biologic differences. (3)  Mortality rates for COPD in women are not trending down as rapidly as in men, and COPD may be underdiagnosed in women due to lack of formal evaluation with spirometry, physician bias, women seeking care later in the disease progression, or associated fatigue or depression misdirecting diagnostic strategies. (4) With respect to asthma, adult females (vs males) have a higher prevalence, a more severe phenotype, tend to be overrepresented in severe asthma cohorts, and have higher health care utilization. Asthma is also the most common chronic respiratory disease during pregnancy. (5) There is “an epidemic” of lung cancer in women globally, with the dominant risk factor being cigarette smoking. Among never-smokers, lung cancer is more common in females, suggesting sex- and gender-related differences in carcinogenesis influenced environmental, genetic, and hormonal factors. (6) Development of several types of interstitial lung disease may be affected by sex, sex hormones, and age. (6) Women with the same symptoms are less often diagnosed and treated for OSA than men.

The review authors noted that women continue to be underdiagnosed for respiratory diseases and may not receive appropriate timely therapies, as some therapies tested only in males have been extrapolated for use in females. “These clinical differences between men and women further emphasize the importance of prompt recognition of possible cases, suitable diagnostic procedures, accurate assessment of the severity of the disease and appropriate treatment,” said the reviewers, adding that, for individuals whose gender does not match their biological sex, there is still a paucity of literature.

Reference

Sodhi A, Pisani M, Glassberg MK, Bourjeily G, D’Ambrosio C. Sex and gender in lung disease and sleep disorders: a state of the art review. Chest. Published online March 14, 2022. doi:10.1016/j.chest.2022.03.006