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

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.
Competing Interests: Declaration of competing interest Z.S. reports payments for lectures, presentations, speakers bureaus, manuscript writing or educational events and support for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated, outside the submitted work. S.G. reports grants with payments made to the institution from Mukoviszidose e.V. (German CF foundation) and Vertex Pharmaceuticals Incorporated, outside the submitted work and personal payments for presentations and advisory boards from Chiesi GmbH and Vertex Pharmaceuticals Incorporated, outside the submitted work. E.S. reports a grant for attending meetings and/or travel from the European Cystic Fibrosis Society, outside of the submitted work. J.R. reports payment for presentations among educational events and attending meetings from Vertex Pharmaceuticals Incorporated, outside the submitted word. Additionally, he is work package leader in BEAT-PCD (ERS-CRC). M.A.M. reports grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and German Innovation Fund with payments to the institution and grants, consulting fees, lecture fees, fees for participation in advisory board and travel reimbursement from Vertex Pharmaceuticals Incorporated, outside the submitted work. Additionally, he reports consulting fees, fees for participation in advisory board and travel reimbursement from Boehringer Ingelheim, outside the submitted work. Further, he reports consulting fees and fees for participation in advisory board from Abbvie, Antabio, Arrowhead, Enterprise Therapeutics and Kither Biotec, outside the submitted work. Furthermore, he reports consulting fees from Prieris, Recode, Santhera, Splisense, outside the submitted work. He further reports personal fees for participation in advisory board from Pari, outside the submitted work. He is a Fellow of ERS (FERS). M.S. reports grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; STA 1685/1–1). She is Chairman of the German CF Research Council (FGM) and Treasurer of the German Society of Paediatric Pulmonology (GPP). All other authors have nothing to disclose.
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