Introduction
Airway nitric oxide (FENO) in people with cystic fibrosis (CF) is lower than normal and ivacaftor results in an early and sustained increase in FENO in treated individuals (Grasemann H et al. Eur Respir J. 2020). The effect of elexacaftor-tezacaftor-ivacaftor (ETI) on airway NO is not known. We aimed to study the effect of ETI on FENO in children with CF.
Methods
This is a prospective observational study in children with CF 6-18 years old and started on ETI therapy. The study was approved by the local REB. FENO was measured before and 1-3 months after ETI initiation at regular clinic visits using a Niox Vero device. Comparisons between pre and post were made with t-test or Wilcoxon test, where appropriate.
Results
Thirty-eight patients (median 14.8 yrs, IQR 11.5-16.9) were included, 21 were male, 24 F508del homozygous, 28 were naïve to CFTR modulator therapy, and 10 switched from lumacaftor-ivacaftor to ETI. Baseline and follow-up FENO (median, IQ range) values are shown in the table.
|
|
F508del/F508del modulator naïve (n=14) |
Switch from lumacaftor-ivacaftor (n=10) | F508del/other modulator naïve (n=14) | |
| FENO (ppb) |
11 (9-15) vs 14 (9-21) |
11 (8-14) vs 13 (9-19) |
12 (8-15) vs 13 (9-25) |
11 (10-20) vs 15 (10-26) |
| p-value | 0.002 | 0.031 | 0.2 | 0.076 |
There was no correlation between FENO or changes in FENO with sweat chloride levels or pulmonary function (FEV1).
Conclusions
ETI results in an increase in FENO in treated children with CF 1-3 months after initiation of therapy. The increase in FENO seems more robust in F508del/F508del patients naïve to CFTR modulator therapy compared to those switched from lumacaftor-ivacaftor or those with a single F508del allele.