Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor |
| |
| Affiliation: | 1. Halo Research Group, Queen''s University Belfast, Belfast, UK;2. Wellcome-Wolfson Institute for Experimental Medicine. School of Medicine, Dentistry and Biomedical Sciences Queen''s University Belfast, Belfast, UK;3. School of Pharmacy, Queen''s University Belfast, Belfast, UK;4. Cork Centre for Cystic Fibrosis, Cork University Hospital, University College Cork, Ireland;5. HRB Clinical Research Facility, University College Cork, Cork, Ireland;6. Department of Medicine, Cork University Hospital, Wilton, Cork, Ireland;1. Monash Lung and Sleep, Monash Medical Centre, 246 Clayton Road, Clayton VIC 3168, Victoria, Australia;2. Monash Centre for Health Research and Implementation, Monash University, Melbourne, Victoria, Australia;3. Monash Children''s Allied Health, Monash Medical Centre, 246 Clayton Road, Clayton VIC 3168, Victoria, Australia;1. Translational Lung Research Center (TLRC), Heidelberg, Germany;2. Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany;3. Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany;4. Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany;5. Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany;6. Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany;7. Berlin Institute of Health (BIH), Berlin, Germany;8. German Center for Lung Research (DZL), associated partner site, Berlin, Germany;9. Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA;10. Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany;1. Department of Respirology, St. Michael''s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada;2. Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada;3. Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto, Canada;4. Keenan Research Centre, Li Ka Shing Knowledge Institute of St Michael''s Hospital, 209 Victoria Street, Toronto, Canada;1. Department of Pulmonary Medicine, University Hospital Essen- Ruhrlandklinik, Essen, Germany;2. Adult Cystic Fibrosis Center, Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, Germany;1. Departments of Medicine and Pediatrics, Medical University of South Carolina, 96 Jonathan Lucas St, Room 812-CSB, MSC 630, Charleston, SC 29425, USA;2. University of Queensland, Level 7, Centre for Child Health Research, Graham St, South Brisbane, Queensland 4101, Australia;3. Lady Cilento Children''s Hospital, 501 Stanley St, South Brisbane 4101, Australia;4. Division of Respirology, Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael''s Hospital, University of Toronto, 1 King''s College Circle, 6263 Medical Sciences Building, Toronto, ON M5S 1A8, Canada;5. Johnson & Johnson Medical Devices, 325 Paramount Dr, Raynham, MA 02767, USA;6. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA;7. Vertex Pharmaceuticals (Europe) Limited, 86-88 Jubilee Avenue, Milton Park, Abingdon, Oxfordshire OX14 4RW, UK;8. National Heart and Lung Institute, Imperial College, London, UK;9. Department of Pediatric Respiratory Medicine, Royal Brompton and Harefield National Health Service Foundation Trust, Sydney Street, London SW3 6NP, UK;10. Department of Pediatrics, University of Colorado School of Medicine, 13123 E 16th Ave, Aurora, CO 80045, USA |
| |
| Abstract: | BackgroundTreatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF.MethodsUsing both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes.ResultsSignificant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59*10−4) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05).ConclusionsFollowing treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
