Elexacaftor-tezacaftor-ivacaftor decreases pseudomonas abundance in the sinonasal microbiome in cystic fibrosis.

Autor: Zemke AC; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hilliam Y; Department of Microbiology & Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA., Stapleton AL; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Kimple AJ; Department of Otolaryngology-Head & Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, USA., Goralski JL; Division of Pulmonary Diseases & CCM, University of North Carolina, Chapel Hill, North Carolina, USA., Shaffer AD; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Pilewski JM; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Senior BA; Department of Otolaryngology-Head & Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, USA., Lee SE; Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Division of Otolaryngology-Head & Neck Surgery, Department of Surgery, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA., Cooper VS; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: International forum of allergy & rhinology [Int Forum Allergy Rhinol] 2024 May; Vol. 14 (5), pp. 928-938. Date of Electronic Publication: 2023 Oct 14.
DOI: 10.1002/alr.23288
Abstrakt: Background: Chronic rhinosinusitis (CRS) is common in individuals with cystic fibrosis (CF) and is marked by chronic inflammation and episodes of infection that negatively impact quality of life. Several studies have shown that elexacaftor-tezacaftor-ivacaftor (ETI) improves symptoms and examination findings in CF-CRS. The current study determines the effect of ETI on the sinonasal microbiota in CF.
Methods: Sinonasal samples were collected under endoscopic visualization before and after starting ETI. Samples were subjected to 16S amplicon sequencing and sequences were processed with the QIIME2 pipeline with subsequent analysis using the vegan R-package.
Results: Twenty-nine individual baseline samples and 23 sample pairs pre-/post-ETI were available. At baseline, the cohort had samples dominated by Staphylococcus, and alpha diversity was lower than that of a published reference set of individuals without sinonasal disease. Individuals with prior sinus surgery had lower alpha diversity as measured by Shannon Index, Observed Richness, and Faith's phylogenetic diversity Index. Beta diversity differed between individuals with and without allergic rhinitis, with higher Staphylococcus abundance in those with allergic rhinitis. No change in alpha or beta diversity was seen after a median of 9 months on ETI. With ETI, the Pseudomonas genus and the genus containing Burkholderia decreased in samples containing these taxa at baseline. Pseudomonas abundance decreased with treatment as measured by qPCR. Core sinonasal microbiome members Staphylococcus, Corynebacterium, and Streptococcus were unchanged, while Moraxella increased with ETI.
Conclusions: Treatment with ETI leads to a reduction in Pseudomonas abundance within the sinonasal microbiome of individuals with Pseudomonas at baseline.
(© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
Databáze: MEDLINE
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