Effect of elexacaftor/tezacaftor/ivacaftor on airway and systemic inflammation in cystic fibrosis.

Autor:	Casey M; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.; Cystic Fibrosis Unit, Beaumont Hospital, Dublin, Ireland., Gabillard-Lefort C; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., McElvaney OF; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., McElvaney OJ; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.; Cystic Fibrosis Therapeutics Development Network, Seattle, Washington, USA., Carroll T; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., Heeney RC; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., Gunaratnam C; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.; Cystic Fibrosis Unit, Beaumont Hospital, Dublin, Ireland., Reeves EP; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland., Murphy MP; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland MMurphy@rcsi.ie., McElvaney NG; Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.; Cystic Fibrosis Unit, Beaumont Hospital, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	Thorax [Thorax] 2023 Aug; Vol. 78 (8), pp. 835-839. Date of Electronic Publication: 2023 May 19.
DOI:	10.1136/thorax-2022-219943
Abstrakt:	Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to improve lung function in people with cystic fibrosis (PWCF). However, its biological effects remain incompletely understood. Here we describe alterations in pulmonary and systemic inflammation in PWCF following initiation of ETI. To address this, we collected spontaneously expectorated sputum and matching plasma from PWCF (n=30) immediately prior to ETI therapy, then again at 3 and 12 months. Within 3 months, PWCF demonstrated reduced activity of neutrophil elastase, proteinase three and cathepsin G, and decreased concentrations of interleukin (IL)-1β and IL-8 in sputum, accompanied by decreased Pseudomonas burden and restoration of secretory leukoprotease inhibitor levels. Once treated with ETI, all airway inflammatory markers studied in PWCF had reduced to levels found in matched non-CF bronchiectasis controls. In PWCF with advanced disease, ETI resulted in decreased plasma concentrations of IL-6, C-reactive protein and soluble TNF receptor one as well as normalisation of levels of the acute phase protein, alpha-1 antitrypsin. These data clarify the immunomodulatory effects of ETI and underscore its role as a disease modifier. Competing Interests: Competing interests: NGM reports consulting fees from Vertex, Inhibrx and Intellia unrelated to the submitted work. (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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