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The themes of sex differences and the role of sex steroids raise the question of whether and how our understanding of sex steroids can be used to clinically and physiologically develop biomarkers to diagnose, monitor, and perhaps treat lung diseases. Interestingly, these animal studies would suggest a lack of direct effect of estrogens on ASM, which appears to be in sharp contrast to the in vitro work especially in human cells. In addition to rapid activation of eNOS in pulmonary endothelium, estrogen stimulates transcriptional up-regulation of NOS , along with down-regulation of the potent vasoconstrictor and smooth muscle mitogen endothelin-1 Here, it would be of interest to explore sex differences in the progression toward COPD in offspring of mothers who smoked or were exposed to secondhand smoke during pregnancy or during the postnatal period. Increased secretion of collagen, fibronectin, laminin, and other profibrotic proteins is not the sole mechanism responsible for development of PF. PF is a progressive disease characterized by inflammation and scarring of the lungs, it affects approximately 5 million persons worldwide, and it is more common in men than women This sex difference may be due in part to differences in environmental exposure between girls and boys, reflecting outdoor and recreational activity patterns

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