Table 1 Summary of proposed biological mechanisms for the sex disparity in CF outcomes
From: Sex disparities in cystic fibrosis in the era of highly effective modulator treatment
Mechanism (references) | |
|---|---|
Anatomical | - Reduced airway diameter and lung volumes in females [23, 24] - Sharp airway branch points and airway bifurcations in females [25] |
Genetic | - Sex-biased expression of genes related to CFTR and inflammation [35] - Increased immunity genes on X chromosome [37] |
Microbiology | - Earlier acquisition of common CF pathogens in females [17, 32, 33] - Earlier acquisition of P.aeruginosa [17, 32, 33] - Female PWCF have more frequent PEx than males [17, 29,30,31] |
CFRD | - CFRD more common among females [12,13,14] - Associated with greater decline in lung function and mortality in female PWCF [12,13,14] - Insulin insufficiency induces catabolic state leading to low BMI [11] |
Sex hormone related | - Estrogen alters ion transport across the epithelium via inhibition of CaCC mediated Cl- secretion [43], reduced CFTR expression [44] and increased ENaC expression at apical cell membranes [46] - Estrogen increases mucin production (MUC5B) [48] - Progesterone reduces ciliary beat frequency [47] - Estrogen induces mucoid conversion of P.aeruginosa [32, 34] - Estrogen inhibits lactoferrin, supporting biofilm development. [52, 53] - Estrogen promotes P.aeruginosa motility, adherence and secretion of pyocyanin [49, 54] - Estrogen reduces neutrophil chemotaxis via downregulation of IL-8 [61] |