Methods
We included patients with CF who had been using lumacaftor/ivacaftor or
ivacaftor for at least 6 months, and who underwent chest CT within 18
months before or after start of therapy. All patients had been in
standardized follow up since the moment before start of the CFTR
modulator: just before start, patients completed a CFQ-R, underwent
pilocarpine iontophoresis sweat chloride testing and pulmonary function
testing and measurement of weight and height. All of these measurements
were repeated after 6 months of treatment.
In patients starting ivacaftor, a low dose high resolution (HRCT) scan
of the chest was performed before the start of treatment in all
patients. In the patients starting lumacaftor/ivacaftor, CT scan of the
chest was performed by indication only, usually for the exclusion of
pulmonary embolism (CT pulmonary angiogram, CTPA: with IV contrast), for
evaluation of actual bleeding in patients with hemoptysis (CTPA), or
when a patient was screened for lung transplant (HRCT).
Due to the scanning protocol and indication, CTPA did not include
expiration slides for evaluation of air trapping. Therefore we
calculated total Brody score without air trapping for the group of
patients starting with lumacaftor/ivacaftor. In the group of patients
who started ivacaftor however, complete Brody score, including air
trapping, was available for all patients and this has been used for
analysis.
For this study, assessment of Brody score was performed by a
board-certified chest radiologist. Brody score was recorded as a total
score, total score excluding air trapping, and separate scores on all
subdomains9. Total scores and subdomain scores were
normalized to a 0-100 scale.
Spirometry was carried out according to the current European Respiratory
Society (ERS) guidelines using reference data from the Global Lung
Function Initiative (GLI) to calculate
ppFEV110,11.
For analysis of the data, IBM SPSS 25 analysis software was used. To
assess correlations, the commonly used Pearson R was calculated. In
addition Spearman R was calculated. We consider the latter the best
applicable method for our purpose, as this method is less sensitive to
outliers and suitable for non-linear correlation. To determine
statistical significance, the cut-off for p-value was set at 0.05.