Sex differences in COPD slow to be recognized, treated


When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.


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