Introduction
This millennium saw a transformation in the way cystic fibrosis (CF), a lethal, autosomal recessive disease affecting over 80,000 people worldwide1, is treated. This monogenic disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene2,3. The altered function of the CFTR protein that is present in multiple epithelia such as the lung, pancreas, gastrointestinal tract, liver, and reproductive tract4,5 causes abnormal viscous secretions and in the airways in particular, chronic infection and exuberant inflammatory response leading to progressive respiratory failure and death if patient cannot get access to a lung transplant6. Historically, treatment of CF has involved symptomatic treatment aiming at increasing mucociliary clearing, preventing infection and inflammation as well as nutritional therapies7-9. Change of treatment paradigm started in 2012, with the availability of the first therapy targeting the CFTR protein basic defect on a small minority of the population carrying at least one gating mutation10,11. This new class of drugs called CFTR modulators (CFTRm) rapidly increased with the addition of new combinations targeting additional CF patient groups, ivacaftor/lumacaftor, ivacaftor/tezacaftor and more recently ivacaftor/tezacaftor/elexacaftor, each of them approved for use in patients with specific genotypes12. Although genotype does not fully correlate with phenotype, patients homozygous forF508del , the most frequently represented mutation worldwide, generally have a rapidly progressive disease while patients with mutations associated with residual function of the CFTR protein tend to have a slower course of disease13. With the increasing availability of compounds addressing the cause of the disease, the possibility to change the course of CF is now within reach and there are high hopes in the community to transform this rapidly lethal disease into a chronic disease. While longer follow up is needed to fully understand the potential of this new class of drugs, treatment decisions can be influenced by the length of personal experience with CFTR modulators, expectations in the longer term and the perception of specific burden of illness by subgroups of mutation types or age range. We conducted this survey among Italian CF physicians to understand their perception and use of CFTRm, checking their treatment preference and opinion on how early treatment should be started in different patient groups with different disease expression. This is the second survey conducted by our group, at 3 year interval from the previous one performed using the same modalities14.