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.