Mild CF

Question

I often read about mild forms of CF. But what is mild? Can you translate this in terms of life expectancy?

Answer

Thank you for this interesting question. Your question is relevant and there are several ways to answer it because the term mild CF is used in different ways.
First and foremost, since the discovery of the CFTR gene we know that some patients have a mutation in each of their CFTR genes but have a much milder clinical picture or a clinical picture or disease in just one organ system (for instance sterility in men). They thus really differ from the classical patient with CF who has early onset disease in the lung, malabsorption, a very abnormal sweat test result and infertility. In these cases of ‘mild CF’ doctors even discuss whether the term cystic fibrosisis is appropriate because in some of these people there is no proof that the disease will shorten their life. Other names that are used for these forms of disease are CFTR related disorder or atypical CF.

But even in patients with classical CF there is a large variation in disease severity. Part of it is explained by the type of mutation that the patient carries. We divide CFTR mutations in 5 categories: class 1 to 3 usually result in severe disease with pancreatic insufficiency; class 4 and 5 mutations are on average associated with a milder course. A milder course then means later age when symptoms start, less severe disease or lower number of organs involved and better life expectancy. Read more about this in the questions on genetics.

But there is even a difference in disease severity and prognosis between patients who carry exactly the same mutation. Even in the group of patients who are homozygous for the F508del mutation (= have that mutation on both CFTR genes). How is that possible? Other genetic factors than the CFTR mutations (we call them modified genes) and environmental factors (such as age of diagnosis, intensity of treatment, how well the treatment is taken, exposure to smoke,.. )also influence disease severity. A way to define mild CF can thus be describing a patient who apparently does better than what is the average result for his mutation class. A mild disease course can be expressed as a better result than 3 quarters of the CF patients in the same age category or better survival than the average patient with CF carrying the same mutations. For F508del homozygous patients the latter would mean patients older than 35 to 40 years.
But please be aware that we can only state many things for groups of patients. In the individual patient it remains very difficult to give any useful prediction. If a patient with classic CF has a mild disease course at a young age this holds no guarantee that his disease course will remain mild throughout his life.

Prof. Dr. K. De Boeck

11.02.2010