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.