Sex Differences in Pulmonary Anatomy and Physiology: Implications for Health and Disease

The physiological and pathophysiological impact of inherent sex differences in pulmonary anatomy and the modulating role of sex steroids (estrogen, progesterone, and testosterone) are being increasingly recognized. Although the importance of estrogen and progesterone in cardiovascular, musculoskeletal, and neuronal function is better established, epidemiological, clinical, and bench research data highlight sex differences in the frequency, morbidity and mortality of pulmonary diseases including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, and even pulmonary hypertension. However, the mechanisms of sex steroid signaling and their contribution to pulmonary diseases are still under investigation, with a fundamental question being whether sex steroids are detrimental or beneficial in the context of lung disease. In this chapter, we focus on inherent sex differences in airway structure and function across the age spectrum, and their potential role in airway disease, with discussion of the potential modulatory role of sex steroids on specific airway cell types that lead to altered lung structure and function in the context of disease.