Introduction
Despite the fact that Cystic Fibrosis (CF) affects various epithelia
throughout the body, its effects on the airway epithelium are usually
the most evident, resulting in structural damage to the airways and lung
parenchyma that can be clearly visualized on computed tomography (CT)
scan of the chest, which is widely used as an additional follow up tool
in CF care1.
F508del is the most common CF causing mutation, present on 66.7% of
alleles in CF patients in Europe, and is even more frequent in the
Netherlands2. It affects folding, trafficking, and
function of the CFTR protein usually leading to a severe CF
phenotype3. Targeted therapy for this mutated protein
consists of a combination of a CFTR corrector, enhancing processing and
trafficking and a potentiator, increasing the open probability of the
chloride channel4. The first available combination
therapy for treatment of F508del homozygous patients regardless of
ppFEV1 is lumacaftor/ivacaftor. In the phase III
randomized clinical trials for this drug, a modest improvement in
FEV1 and BMI and a significant decrease in pulmonary
exacerbations was observed in comparison to placebo. However, the
effects of this drug proved to be highly variable in the phase III
studies, as well as in clinical practice5,6.
The effect of ivacaftor for patients with gating mutations such as G551D
and S1251N, is overall better in comparison with lumacaftor/ivacaftor,
especially on sweat chloride concentrations and lung function, but these
effects also vary between individuals7,8.
As the structural damage in CF lung disease involves longstanding
remodeling of airways and lung parenchymal fibrosis, we do not expect
this structural damage, nor its effect on FEV1, to
change after the initiation of therapy. Therefore, the aim of this study
was to evaluate if the extent of structural damage to the lungs visible
on chest scans is correlated with the response in ppFEV1 after
initiation of CFTR modulatory (ivacaftor or lumacaftor/ivacaftor)
therapy in CF patients.