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Ivacaftor/lumacaftor changes the lung microbiome and metabolome in cystic fibrosis patients

Anne H. Neerincx, Katrine Whiteson, Joann L. Phan, Paul Brinkman, Mahmoud I. Abdel-Aziz, Els J.M. Weersink, Josje Altenburg, Christof J. Majoor, Anke-H. Maitland-Van Der Zee, Lieuwe D.J. Bos
European Respiratory Journal 2020 56: 4337; DOI: 10.1183/13993003.congress-2020.4337
Anne H. Neerincx
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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  • For correspondence: a.vanstuyvenbergneerincx@amsterdamumc.nl
Katrine Whiteson
2Whiteson Lab , University of California Irvine, Irvine, California, United States of America
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Joann L. Phan
2Whiteson Lab , University of California Irvine, Irvine, California, United States of America
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Paul Brinkman
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Mahmoud I. Abdel-Aziz
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Els J.M. Weersink
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Josje Altenburg
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Christof J. Majoor
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Anke-H. Maitland-Van Der Zee
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Lieuwe D.J. Bos
1Department of Respiratory Medicine, Amsterdam UMC – Location AMC, University of Amsterdam , Amsterdam, Netherlands
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Abstract

Introduction: Targeted cystic fibrosis (CF) therapy with ivacaftor/lumacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes in the microbiome that is adapted to CF lungs may occur.

Objective: To investigate the effects of ivacaftor/lumacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract.

Methods: This was a single-center longitudinal observational cohort study in adult CF patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and an exhaled breath sample were collected before and every 3 months after starting therapy, up to one year.

Results: Twenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that Pseudomonas aeruginosa was most abundant in sputum and seemed to decrease after 6 months of treatment. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months after treatment that almost returned to baseline levels after 12 months follow-up. The volatile metabolic composition of breath was significantly different after 3 months of treatment and remained different from baseline until 12 months after treatment.

Conclusions: After starting cystic fibrosis transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in the lung microbiome is observed, which is mainly characterized by a reduction in the relative abundance of Pseudomonas aeruginosa.

  • Cystic fibrosis
  • Adults
  • Mirobiome/Microbiota

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4337.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Ivacaftor/lumacaftor changes the lung microbiome and metabolome in cystic fibrosis patients
Anne H. Neerincx, Katrine Whiteson, Joann L. Phan, Paul Brinkman, Mahmoud I. Abdel-Aziz, Els J.M. Weersink, Josje Altenburg, Christof J. Majoor, Anke-H. Maitland-Van Der Zee, Lieuwe D.J. Bos
European Respiratory Journal Sep 2020, 56 (suppl 64) 4337; DOI: 10.1183/13993003.congress-2020.4337

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Ivacaftor/lumacaftor changes the lung microbiome and metabolome in cystic fibrosis patients
Anne H. Neerincx, Katrine Whiteson, Joann L. Phan, Paul Brinkman, Mahmoud I. Abdel-Aziz, Els J.M. Weersink, Josje Altenburg, Christof J. Majoor, Anke-H. Maitland-Van Der Zee, Lieuwe D.J. Bos
European Respiratory Journal Sep 2020, 56 (suppl 64) 4337; DOI: 10.1183/13993003.congress-2020.4337
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