Sex Differences in Chronic Obstructive Pulmonary Disease: Implications for Pathogenesis, Diagnosis, and Treatment

Chronic obstructive pulmonary disease (COPD) is a leading chronic disease worldwide, with significant healthcare utilization, morbidity, and mortality. Irreversible airflow obstruction identified on spirometry establishes the diagnosis of COPD, but the disease entity encompasses a heterogeneous collection of lung diseases, including chronic bronchitis and emphysema. Despite the enormous burden of COPD, there are no pharmacological therapies that slow its progression or reduce mortality, indicating the need for a deeper understanding. There are sex differences concerning COPD prevalence, pathology, and symptoms. Historically thought to primarily affect males, its effect on females has increased significantly over time due to a rising prevalence of smoking and exposure to harmful pollutants among females. Over the past decade, the age-adjusted prevalence of COPD has been consistently higher in females than in males. Despite this, the impacts of biological sex continue to be confusing and poorly defined. The primary goal of this review is to organize and collate sex-dependent factors that may contribute to disease differences in males and females, thereby identifying future research questions in this area.