Sex, gender and the pulmonary physiology of exercise

In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.

Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease

Two highly prevalent pulmonary diseases, lung cancer and chronic obstructive lung disease (COPD), show both sex and gender differences in their presentations and outcomes. Sex differences are defined as biological differences associated with the male versus female genotype, and gender differences are defined as behavioral or social differences that primarily arise because of gender identity. The incidence of both lung cancer and COPD has increased dramatically in women over the past 50 years, and both are associated with chronic pulmonary inflammation. Development of COPD is also a risk factor for lung cancer. In this review, the main differences in lung cancer and COPD biology observed between men and women will be summarized. Potential causative factors will be discussed, including the role of estrogen in promoting pro-growth and inflammatory phenotypes which may contribute to development of both lung cancer and COPD. Response of the innate and adaptive immune system to estrogen is a likely factor in the biology of both lung cancer and COPD. Estrogen available from synthesis by reproductive organs as well as local pulmonary estrogen synthesis may be involved in activating estrogen receptors expressed by multiple cell types in the lung. Estrogenic actions, although more pronounced in women, may also have importance in the biology of lung cancer and COPD in men. Effects of estrogen are also timing and context dependent; the multiple cell types that mediate estrogen action in the lungs may confer both positive and negative effects on disease processes.

Gender-Related Differences in Chest Pain Syndromes in the Frontiers in CV Medicine Special Issue: Sex & Gender in CV Medicine

Coronary artery disease (CAD) is the leading cause of morbidity and mortality among both women and men, yet women continue to have delays in diagnosis and treatment. The lack of recognition of sex-specific biological and socio-cultural gender-related differences in chest pain presentation of CAD may, in part, explain these disparities. Sex and gender differences in pain mechanisms including psychological susceptibility, the autonomic nervous system (ANS) reactivity, and visceral innervation likely contribute to chest pain differences. CAD risk scores and typical/atypical angina characterization no longer appear relevant and should not be used in women and men. Women more often have ischemia with no obstructive CAD (INOCA) and myocardial infarction, contributing to diagnostic and therapeutic equipoise. Existing knowledge demonstrates that chest pain often does not relate to obstructive CAD, suggesting a more thoughtful approach to percutaneous coronary intervention (PCI) and medical therapy for chest pain in stable obstructive CAD. Emerging knowledge regarding the central and ANS and visceral pain processing in patients with and without angina offers explanatory mechanisms for chest pain and should be investigated with interdisciplinary teams of cardiologists, neuroscientists, bio-behavioral experts, and pain specialists. Improved understanding of sex and gender differences in chest pain, including biological pathways as well as sociocultural contributions, is needed to improve clinical care in both women and men.

A Systematic Review of the Sex and Gender Reporting in COVID-19 Clinical Trials

Sex and gender have implications for COVID-19 vaccine efficacy and adverse effects from the vaccine. As vaccination is one of the key responses to the COVID-19 pandemic, it is vital that sex and gender differences be acknowledged, measured, and analysed in clinical research. Here, we systematically review published COVID-19 vaccine trials, both interventional and observational, to assess the quality of reporting of sex and gender. Of the 75 clinical trials on COVID-19 vaccines included in this review, only 24% presented their main outcome data disaggregated by sex, and only 13% included any discussion of the implications of their study for women and men. Considering the sex differences in adverse events after vaccination, and the gendered aspects of vaccine hesitancy, these oversights in clinical research on vaccines have implications for recovery from the COVID-19 pandemic and for wider public health.