Author
Hilal Ersöz, Thorax Clinic Heidelberg, as published in Alpha1 Journal 2/2024.
Gender medicine initially emerged from the women's rights movement and women's health research in the USA in the 1980s. It now occupies an important place in both science and clinical practice and is essential for improving men's and women's health. It investigates biological differences as well as gender-related sociocultural influences on diseases and the experience of illness.
Gender-specific differences in alpha 1-antitrypsin deficiency
Due to the small number of patients in individual countries and centers, it is particularly difficult to investigate the gender-specific aspects of rare diseases, which is why no meaningful data on this topic exist for AATM. Therefore, our aim was to investigate the gender issue using the prospective international registry of the European Alpha-1 Research Collaboration (EARCO) for patients with AATM.
Gender-specific differences in patient characteristics
The gender question was specifically investigated in patients with the PiZZ genotype. Men in this cohort had a higher BMI. Women were more likely to have the disease diagnosed through family screening, whereas they were less likely to present with liver disease.
Gender-specific differences in exposure
Compared to male study participants, women were more likely to be never-smokers or to report a lower total nicotine consumption, measured in pack-years. Exposure to other inhalable substances such as biomass, cocaine, e-cigarettes, or marijuana was rare and showed no significant differences between the sexes. However, occupational exposure did reveal differences between the sexes: men were more frequently exposed to gases, fumes, dust, asbestos, or other substances than women. Differences also existed in alcohol consumption: women reported less active alcohol consumption, and the number of units of alcohol consumed per week was lower.
Sex-specific differences in lung and liver diseases associated with alpha-1 antitrypsin deficiency
Looking at lung diseases associated with alpha-1 antitrypsin deficiency, men were more likely to have COPD, pulmonary emphysema, or chronic bronchitis, while female participants were more likely to have bronchiectasis. Regarding liver disease, male participants were more likely to have liver disease, cirrhosis, fibrosis, or fatty liver.
Figure 1: Gender-specific differences regarding lung and liver disease
Gender-specific differences in comorbidities
Regarding comorbidities, men had higher rates of ischemic heart disease and pulmonary embolism. Women, on the other hand, had higher rates of connective tissue disease, osteoporosis, and depression.
Figure 2: Gender-specific differences in comorbidities
Gender-specific differences in the COPD subgroup of the EARCO registry
When specifically examining patients with alpha-1 antitrypsin deficiency and COPD, differences in risk behavior are initially apparent: Men reported a higher total nicotine consumption, measured in pack-years. Regarding COPD severity, women with COPD were more frequently classified as GOLD grade 1 (mild COPD) and less frequently as GOLD grade 4 (very severe COPD) than men. Nevertheless, women with COPD exhibited a significantly higher symptom burden. Furthermore, women in this subgroup reported at least one exacerbation in the past year more frequently than men.
Independent risk factors for symptom burden and exacerbation
Additional analyses were conducted to investigate potential influencing factors such as smoking status, COPD, and sex on symptom burden or exacerbation. In these studies, female sex emerged as an independent risk factor for increased symptom burden and the occurrence of at least one exacerbation within the past 12 months.
Conclusion
Gender appears to play a role in alpha-1 antitrypsin deficiency in many ways. Due to differences in risk behavior, gender should be given greater consideration in alcohol and tobacco prevention programs. Differences in lung diseases, such as the prevalence of COPD and emphysema in men and bronchiectasis in women, highlight the need for tailored treatment approaches that take gender into account. It is hoped that further research in this area will lead to a better understanding of the relationships and causes of these differences and to the development of gender-adapted treatment strategies.
