Cystic fibrosis: why are women more at risk than men?

Today in France, approximately 6,000 people are affected by cystic fibrosis. Each year, nearly 200 children are born with this hereditary genetic disease. Cystic fibrosis mainly affects the lungs, but it also affects other organs, including those of the digestive system and the reproductive system.

Cystic fibrosis: lower life expectancy for women

Routine screening for cystic fibrosis at birth has revealed that the numbers of male and female newborns with cystic fibrosis are similar. However, one thing raises questions about this condition: young patients develop an earlier and more severe lung disease than boys and the mortality of women with cystic fibrosis is higher than that of men. Their life expectancy is thus 49 years on average, compared to 56 for men, contrary to what is observed in the general population. Why don’t the two sexes have the same chances of survival?

This is the question that Valérie Urbach, an INSERM researcher at the Mondor Institute for Biomedical Research (Créteil), tried to answer. She talks about it in an article from The Conversation : the latter recently made a discovery with her team which could explain, at least in part, the greater vulnerability of sick women compared to men.

Persistent inflammation due to repeated infections

“Our work has revealed that certain molecules involved in interrupting inflammation are produced in insufficient quantities by the respiratory cells of women with cystic fibrosis”, she explains. The cause ? “an anomaly of the CFTR gene, which normally makes it possible to produce a ‘channel’ protein located in the cell membrane of the mucous membranes (respiratory, digestive, etc.). This channel is responsible for the secretion of chloride ions to the outside of the cells”, adds the researcher. However, it is this channel that malfunctions in patients affected by cystic fibrosis. Consequences : “The cells secrete less chloride and especially less water, especially on the surface of the respiratory tract.”

And this lack of water has great repercussions. Indeed, normally, the airways are covered with a thin layer of liquid and mucus that kills germs that have entered the body through the nose or mouth. “When this layer is dehydrated, the mucus becomes slimy and sticky. It no longer fulfills its function correctly, which is why in patients with cystic fibrosis, bacteria and fungi therefore remain trapped in the bronchi”, explains Valérie Urbach. The repeated infections caused by this situation lead to the development of lasting inflammation in the lungs, which gradually degrades them. This can cause difficulty in breathing and ultimately the death of sufferers.

Acting on PMS, a promising therapeutic avenue

Rather than preventing the onset of the usually protective inflammatory response, “a promising therapeutic avenue is to stimulate the resolution of inflammation”, underlines the researcher. The latter is orchestrated by various molecules called lipoxins, resolvins, maresins and protectins, from the family of “specialized pro-resolving mediators” (or SPM). “Fire soldiers”, very important for extinguishing the fire of inflammation within our organism. They are also involved in the repair of tissues damaged during the acute phase of inflammation. “The increased inflammation is not the only explanation for the disease. Indeed, in patients, the inflammatory reaction is, moreover, inefficient and disproportionate; it is even sometimes observed in the absence of microbial infection”says the scientist.

The observations made by his research team could provide the beginning of an explanation for this situation: “We have shown that several members of the family of inflammation-resolving molecules, the SPMs, are produced in lower quantities by the respiratory cells of women with cystic fibrosis compared to those of men. We are now seeking to identify the molecular mechanisms involved in this anomaly, with the hope of uncovering new therapeutic leads.”

This work could also make it possible to better understand the situation of other patients, because the study of molecules involved in the resolution of inflammation is of interest that extends well beyond cystic fibrosis alone, as Valérie Urbach reminds us. Indeed, similar abnormalities have also been observed for other diseases (chronic inflammatory diseases such as periodontitis, inflammation of the gums, multiple sclerosis, cardiovascular diseases, severe asthma, or even Covid-19). 19).