Lumacaftor/ivacaftor changes the lung microbiome and metabolome in cystic fibrosis patients
| Autor: | Neerincx, Anne H., Whiteson, Katrine, Phan, Joann L., Brinkman, Paul, Abdel-Aziz, Mahmoud I., Weersink, Els J.M., Altenburg, Josje, Majoor, Christof J., Maitland-van der Zee, Anke H., Bos, Lieuwe D.J., Haarman, E., Rutjes, N. W., Terheggen-Lagro, S. W.J., Seljogi, D., Kemper, E. M., Lutter, R., Vijverberg, S. J., Vonk, S. E.M., Adriaens, N., Lub, R., van Brederode, M., van der Schaaf, L., Verkleij, M., van Gilst, N. A., Hofsteenge, G. H., Brackel, C. L.H., Lakeman, P., Bon, I. C.M., Tanner, S. P.M., Sterk, P. J., Longo, C., Sinha, A., Fenn, D., Lammers, A., Richards, L. B., van Bragt, J. M., Kos, R., Dagelet, J. W.F., Lone-Latif, S. J.A., Schultz, M. J., Smit, M. R., Hagens, L. A. |
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| Přispěvatelé: | Pulmonary medicine, Pediatrics, Amsterdam Reproduction & Development (AR&D), Psychiatry, CCA - Cancer biology and immunology, Pulmonology, AII - Inflammatory diseases, Graduate School, APH - Personalized Medicine, Paediatric Pulmonology, Intensive Care Medicine, ACS - Heart failure & arrhythmias |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Lung microbiome medicine.medical_specialty Cystic Fibrosis medicine.disease_cause Cystic fibrosis Gastroenterology Ivacaftor 03 medical and health sciences chemistry.chemical_compound Internal medicine Medicine Microbiome 030304 developmental biology 0303 health sciences 030306 microbiology business.industry Pseudomonas aeruginosa Lumacaftor Original Articles medicine.disease Epithelial fluid transport chemistry Sputum medicine.symptom business medicine.drug |
| Zdroj: | Neerincx, A H, Whiteson, K, Phan, J L, Brinkman, P, Abdel-Aziz, M I, Weersink, E J M, Altenburg, J, Majoor, C J, Maitland-van der Zee, A H, Bos, L D J, Haarman, E, Rutjes, N W, Terheggen-Lagro, S W J, Seljogi, D, Kemper, E M, Lutter, R, Vijverberg, S J, Vonk, S E M, Adriaens, N, Lub, R, van Brederode, M, van der Schaaf, L, Verkleij, M, van Gilst, N A, Hofsteenge, G H, Brackel, C L H, Lakeman, P, Bon, I C M, Tanner, S P M, Sterk, P J, Longo, C, Sinha, A, Fenn, D, Lammers, A, Richards, L B, van Bragt, J M, Kos, R, Dagelet, J W F, Lone-Latif, S J A, Schultz, M J, Smit, M R, Hagens, L A, Amsterdam mucociliary clearance disease research group & Amsterdam UMC Breath Research Group 2021, ' Lumacaftor/ivacaftor changes the lung microbiome and metabolome in cystic fibrosis patients ', ERJ Open Research, vol. 7, no. 2, 00731-2020 . https://doi.org/10.1183/23120541.00731-2020 ERJ Open Research, 7(2):00731-2020. BMJ Publishing Group ERJ Open Research article-version (VoR) Version of Record ERJ open research, 7(2):00731-2020. European Respiratory Society ERJ Open Research, Vol 7, Iss 2 (2021) |
| ISSN: | 2312-0541 2044-6055 |
| DOI: | 10.1183/23120541.00731-2020 |
| Popis: | Rationale Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes may occur in the microbiome, which is adapted to CF lungs. Objectives To investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract. Methods This was a single-centre 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 a breath sample, were collected before and every 3 months after starting therapy, for up to 12 months. 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, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow-up. Conclusions After starting CF 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 characterised by a reduction in the relative abundance of Pseudomonas aeruginosa. Lumacaftor/ivacaftor in adult cystic fibrosis patients with homozygous Phe508del results in temporal and moderate changes in lung microbiome and metabolome, that are mainly characterised by a reduction in the relative abundance of Pseudomonas aeruginosa https://bit.ly/3pcPUfX |
| Databáze: | OpenAIRE |
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