Elexacaftor/tezacaftor/ivacaftor improves nasal nitric oxide in patients with cystic fibrosis

J Cyst Fibros. 2024 Sep;23(5):863-869. doi: 10.1016/j.jcf.2024.03.003. Epub 2024 Mar 19.

Abstract

Background: In health, nitric oxide (NO) shows high concentrations in the upper airways, while nasal NO (nNO) is significantly lower in patients with sinonasal inflammation, such as people with cystic fibrosis (PwCF). In PwCF treated with elexacaftor/tezacaftor/ivacaftor (ETI; PwCF-ETI), clinical improvement of sinonasal symptoms and inflammation was observed. We therefore hypothesised that ETI may increase nNO in PwCF.

Methods: 25 PwCF-ETI underwent nNO measurement at baseline and after 3 to 24 months of ETI treatment. NNO was measured using velum closure (VC) techniques in cooperative patients and tidal breathing (TB) for all patients. As controls, 7 CF patients not eligible for ETI (PwCF-non ETI) and 32 healthy controls (HC) were also repeatedly investigated.

Results: In PwCF-ETI, sinonasal symptoms, lung function parameters and sweat chloride levels improved from baseline to follow-up whereas there was no change in PwCF-non ETI and HC. NNO increased from a median (IQR) value at baseline to follow-up from 348.2 (274.4) ppb to 779.6 (364.7) ppb for VC (P < 0.001) and from 198.2 (107.0) ppb to 408.3 (236.1) ppb for TB (P < 0.001). At follow-up, PwCF-ETI reached nNO values in the normal range. In PwCF-non ETI as well as HC, nNO did not change between baseline and follow-up.

Conclusions: In PwCF-ETI, the nNO values significantly increased after several months of ETI treatment in comparison to baseline and reached values in the normal range. This suggests that nNO is a potential non-invasive biomarker to examine sinonasal inflammatory disease in PwCF and supports the observation of clinical improvement in these patients.

Keywords: Children; Nasal nitric oxide; Non-invasive outcome measure; Sinonasal disease.

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols* / administration & dosage
  • Aminophenols* / therapeutic use
  • Benzodioxoles* / administration & dosage
  • Benzodioxoles* / therapeutic use
  • Chloride Channel Agonists / therapeutic use
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / physiopathology
  • Drug Combinations*
  • Female
  • Humans
  • Indoles* / administration & dosage
  • Indoles* / therapeutic use
  • Male
  • Nitric Oxide* / analysis
  • Nitric Oxide* / metabolism
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / therapeutic use
  • Pyridines / administration & dosage
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / therapeutic use
  • Quinolones* / administration & dosage
  • Quinolones* / therapeutic use
  • Respiratory Function Tests / methods
  • Sinusitis / drug therapy
  • Treatment Outcome
  • Young Adult

Substances

  • Benzodioxoles
  • Nitric Oxide
  • Indoles
  • Aminophenols
  • Quinolones
  • Drug Combinations
  • Pyrazoles
  • Pyridines
  • Pyrrolidines
  • elexacaftor
  • tezacaftor
  • Chloride Channel Agonists