Use and development of statistical mediation techniques to understand the survival gap between males and females with cystic fibrosis

Cystic Fibrosis (CF) is a life limiting genetic disorder affecting over 70,000 people worldwide. It is caused by a mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene which supplies the instructions for the cystic fibrosis transmembrane conductance regulator protein which acts as a channel to transport chloride and bicarbonate ions across cell membranes. This impaired transport results in thickened and dehydrated mucus covering the cells that both interferes with normal functioning and is prone to colonisation by pathogens causing progressive damage in many organ systems of the body including the pancreas, lungs, kidneys and digestive system, and ultimately leads to a reduced life-span.

Current treatments concentrate on mitigating the damage caused by CF since currently there are no treatments that can cure CF. For babies born in 2019 in the UK, median survival is predicted to be 51.6 years for males and 45.7 years for females. This survival gap between males and females has been present in recorded data over recent decades even as survival times have increased and it has also been observed in other countries. There is as yet no clear explanation for this survival gap and it provides the motivation for this project. It seems likely that sex impacts on several aspects of disease progression through the life course, which in turn affects survival. Previous research has shown that: females with CF first acquire many pathogens at an earlier age than males, females infected with particular pathogens have increased mortality compared to men, after the age of 40 females have greater decline in FEV% predicted (the proportion of Forced Expiratory Volume compared to a person without CF of the same age, sex, height and ethnicity) than males and also that, of those with severe CFTR genotypes, females have higher prevalence of cystic fibrosis related diabetes. The hypothesis is that these and other aspects of disease progression affected by sex are, in...