Sex differences in susceptibility, severity, and progression are prevalent for various diseases in multiple organ systems. This phenomenon is particularly apparent in respiratory diseases. Asthma demonstrates an age-dependent pattern of sexual dimorphism. However, marked differences between males and females exist in other pervasive conditions such as chronic obstructive pulmonary disease (COPD) and lung cancer. The sex hormones estrogen and testosterone are commonly considered the primary factors causing sexual dimorphism in disease. However, how they contribute to differences in disease onset between males and females remains undefined. The sex chromosomes are an under-investigated fundamental form of sexual dimorphism. Recent studies highlight key X and Y-chromosome-linked genes that regulate vital cell processes and can contribute to disease-relevant mechanisms. This review summarises patterns of sex differences in asthma, COPD and lung cancer, highlighting physiological mechanisms causing the observed dimorphism. We also describe the role of the sex hormones and present candidate genes on the sex chromosomes as potential factors contributing to sexual dimorphism in disease.
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