Aim Cystic Fibrosis conductance Transmembrane Regulator (CFTR) protein modulators represent a major breakthrough in the pharmacological management of Cystic Fibrosis (CF). Previous studies report acute changes in lung function after first administration of lumacaftor/ivacaftor (LUM/IVA) without a clear underlying mechanism.^{1 2} Our aim was to explore links between changes in percent predicted forced expiratory volume in one second (ppFEV1) and a number of potentially influencing factors.

Methods We conducted a retrospective review of all children with CF who were started on LUM/IVA treatment between September 2016 and August 2017 in our institution. Data was collected from patient charts, electronic laboratory and radiology records. CT Thorax images were reviewed for evidence of air trapping using the Brody score.³ Descriptive and statistical analyses were performed using SPSS.

Results Data was collected from 15 children with CF who were started on LUM/IVA treatment. The mean (±SD) age of starting treatment was 14 years (±1.7 years), with a mean weight of 47.3 kg (±8.9 kg) and male-to-female ratio of 9:6. Ninety-three percent of patients experienced an acute decline in ppFEV1 post initiation of LUM/IVA, with an absolute mean decline of -10.8% (0–20%). There is a statistically significant inverse relationship between absolute change in ppFEV1 (FEV1) and baseline ppFEV1. There is no correlation between FEV1 and weight, gender or air trapping score.

Conclusion Our results suggest that a LUM/IVA related decline in lung function is more significant in CF children with higher baseline ppFEV1. This offers reassurance when initiating LUM/IVA as the patients who experience significant declines have a greater respiratory reserve with which to support this reduction.

References

1. Ratjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2017;5:557–567.

2. Labaste A, Ohlmann C, Mainguy C, et al. Real-life acute lung function changes after lumacaftor/ivacaftor first administration in paediatric patients with cystic fibrosis. J Cyst Fibros 2017;16:709–712.

3. Brody A, Klein J, Molina P, et al. High- resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. Journal of Pediatrics 2004;145:32–38.