Academic Journal
Long-term therapy with elexacaftor/tezacaftor/ivacaftor improves cystic fibrosis lung disease and monocyte function.
| Τίτλος: | Long-term therapy with elexacaftor/tezacaftor/ivacaftor improves cystic fibrosis lung disease and monocyte function. |
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| Συγγραφείς: | Sangiorgi G; Department of Biology and Biotechnology 'C. Darwin' Sapienza University, Rome, Italy., Cavinato L; Department of Molecular Microbiology, Washington University in St Louis, Missouri, USA., Cristoferi M; Department of Biology and Biotechnology 'C. Darwin' Sapienza University, Rome, Italy., Chiappetta D; Department of Basic and Applied Sciences for Engineering, Sapienza University, Rome, Italy., Pastore V; Department of Biology and Biotechnology 'C. Darwin' Sapienza University, Rome, Italy., Cimino G; Regional Cystic Fibrosis Center, AOU Policlinico Umberto I - Sapienza University, Rome, Italy., Cimino L; Regional Cystic Fibrosis Center, AOU Policlinico Umberto I - Sapienza University, Rome, Italy., Ascenzioni F; Department of Biology and Biotechnology 'C. Darwin' Sapienza University, Rome, Italy., Del Porto P; Department of Biology and Biotechnology 'C. Darwin' Sapienza University, Rome, Italy. Electronic address: paola.delporto@uniroma1.it. |
| Πηγή: | Respiratory medicine [Respir Med] 2026 Aug-Sep; Vol. 260, pp. 108930. Date of Electronic Publication: 2026 Jun 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 8908438 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3064 (Electronic) Linking ISSN: 09546111 NLM ISO Abbreviation: Respir Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : Oxford : Elsevier Original Publication: London : Baillière Tindall, in association with the British Thoracic Society, [c1989- |
| Ιατρικοί όροι (MeSH): | Monocytes*/drug effects , Monocytes*/metabolism , Monocytes*/physiology , Cystic Fibrosis*/drug therapy , Cystic Fibrosis*/physiopathology , Cystic Fibrosis*/microbiology , Aminophenols*/therapeutic use , Aminophenols*/pharmacology , Indoles*/therapeutic use , Indoles*/pharmacology , Indoles*/administration & dosage , Benzodioxoles*/therapeutic use , Benzodioxoles*/pharmacology , Quinolones*/therapeutic use , Quinolones*/pharmacology , Quinolones*/administration & dosage , Pyridines*/therapeutic use , Pyridines*/pharmacology , Pyrazoles*/therapeutic use , Pyrrolidines*/therapeutic use , Pyrroles*/therapeutic use, Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Phagocytosis/drug effects ; Pseudomonas aeruginosa/drug effects ; RNA, Messenger/metabolism ; Pseudomonas Infections/drug therapy ; Chloride Channel Agonists/therapeutic use ; Humans ; Female ; Male ; Drug Combinations ; Adult ; Young Adult ; Quinolines |
| Περίληψη: | Background: Elexacaftor/tezacaftor/ivacaftor (ETI) therapy rapidly improves monocyte antimicrobial activity in people with cystic fibrosis (pwCF). Here, we investigated the effect of long-term ETI therapy on Pseudomonas aeruginosa phagocytosis and on CFTR expression and function in monocytes. Methods: Clinical information and biospecimens were obtained from 60 pwCF at initiation and after 12-48 months of ETI therapy. Monocyte phagocytosis was evaluated by flow cytometry after infection of PBMCs with P. aeruginosa expressing GFP. CFTR protein and mRNA levels were assessed by Western blot and qRT-PCR respectively. CFTR channel activity was evaluated by halide efflux assay. For comparison, measurements were also performed in non-CF subjects. Results: Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and microbiology from 12 months and up to 48 months after the initiation of ETI therapy. ETI therapy resulted in a significant increase in monocyte P. aeruginosa phagocytosis reaching levels similar to non-CF monocytes. A significant increase in the levels of CFTR protein but not mRNA was observed in monocytes during the first 12-36 months of ETI therapy compared to pre-therapy. The expression of CFTR protein and channel function remained significantly lower than those of non-CF monocytes during ETI therapy. Conclusion: Our data suggest that the beneficial clinical effect of long-term ETI therapy is accompanied by an increase in monocyte P. aeruginosa phagocytosis while the CFTR protein expression and function remain lower with respect to non-CF monocytes. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare they have no competing interests or personal relationships that could have influenced the work. |
| Substance Nomenclature: | 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) 0 (Aminophenols) 0 (Indoles) 0 (Benzodioxoles) 0 (Quinolones) 0 (Drug Combinations) 0 (Pyridines) 0 (Pyrazoles) 0 (Pyrrolidines) 0 (RNA, Messenger) 0 (Pyrroles) 0 (Chloride Channel Agonists) 0 (elexacaftor, ivacaftor, tezacaftor drug combination) 0 (CFTR protein, human) 0 (Quinolines) |
| Entry Date(s): | Date Created: 20260605 Date Completed: 20260626 Latest Revision: 20260626 |
| Update Code: | 20260626 |
| DOI: | 10.1016/j.rmed.2026.108930 |
| PMID: | 42248371 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-3064 |
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| DOI: | 10.1016/j.rmed.2026.108930 |