Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents.

Autor: Thorsen J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, and., Stokholm J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Department of Food Science, University of Copenhagen, Frederiksberg, Denmark., Rasmussen MA; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.; Department of Food Science, University of Copenhagen, Frederiksberg, Denmark., Roggenbuck-Wedemeyer M; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.; Novozymes, Bagsvaerd, Denmark., Vissing NH; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital., Mortensen MS; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Brejnrod AD; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Fleming L; National Heart and Lung Institute, Imperial College, London, United Kingdom.; Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom., Bush A; National Heart and Lung Institute, Imperial College, London, United Kingdom.; Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom., Roberts G; Clinical and Experimental Sciences, and.; Human Development and Health, Faculty of Medicine, University of Southampton, United Kingdom.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Singer F; Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Frey U; University Children's Hospital (UKBB), University of Basel, Basel, Switzerland., Hedlin G; Karolinska Institutet, Department of Women's and Children's Health and Astrid Lindgren Children's Hospital, Stockholm, Sweden., Nordlund B; Karolinska Institutet, Department of Women's and Children's Health and Astrid Lindgren Children's Hospital, Stockholm, Sweden., Murray CS; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.; NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Abdel-Aziz MI; Department of Respiratory Medicine, Amsterdam UMC and., Hashimoto S; Department of Respiratory Medicine, Amsterdam UMC and.; Department of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., van Aalderen W; Department of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Maitland-van der Zee AH; Department of Respiratory Medicine, Amsterdam UMC and.; Department of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Shaw D; Division of Respiratory Medicine, University of Nottingham, Nottingham, United Kingdom., Fowler SJ; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.; NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom., Sousa A; Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, London, United Kingdom., Sterk PJ; Department of Respiratory Medicine, Amsterdam UMC and., Chung KF; National Heart and Lung Institute, Imperial College, London, United Kingdom.; Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom., Adcock IM; National Heart and Lung Institute, Imperial College, London, United Kingdom.; NIHR Imperial Biomedical Research Centre, London, United Kingdom., Djukanovic R; Clinical and Experimental Sciences, and.; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Auffray C; European Institute for Systems Biology and Medicine, Vourles, France., Bansal AT; Acclarogen Ltd, Cambridge, United Kingdom; and., Wagers S; BioSci Consulting, Maasmechelen, Belgium., Chawes B; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital., Bønnelykke K; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital., Sørensen SJ; Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark., Bisgaard H; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital.
Jazyk: angličtina
Zdroj: Annals of the American Thoracic Society [Ann Am Thorac Soc] 2022 Dec; Vol. 19 (12), pp. 2031-2043.
DOI: 10.1513/AnnalsATS.202110-1152OC
Abstrakt: Rationale: There is a major unmet need for improving the care of children and adolescents with severe asthma and wheeze. Identifying factors contributing to disease severity may lead to improved diagnostics, biomarkers, or therapies. The airway microbiota may be such a key factor. Objectives: To compare the oropharyngeal airway microbiota of children and adolescents with severe and mild/moderate asthma/wheeze. Methods: Oropharyngeal swab samples from school-age and preschool children in the European U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) multicenter study of severe asthma, all receiving severity-appropriate treatment, were examined using 16S ribosomal RNA gene sequencing. Bacterial taxa were defined as amplicon sequence variants. Results: We analyzed 241 samples from four cohorts: A) 86 school-age children with severe asthma; B) 39 school-age children with mild/moderate asthma; C) 65 preschool children with severe wheeze; and D) 51 preschool children with mild/moderate wheeze. The most common bacteria were Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7.0%), Prevotella (5.9%), and Rothia (5.5%). Age group (school-age vs. preschool) was associated with the microbiota in β-diversity analysis ( F  = 3.32, P  = 0.011) and in a differential abundance analysis (28 significant amplicon sequence variants). Among all children, we found no significant difference in the microbiota between children with severe and mild/moderate asthma/wheeze in univariable β-diversity analysis ( F  = 1.99, P  = 0.08, N  = 241), but a significant difference in a multivariable model ( F  = 2.66, P  = 0.035), including the number of exacerbations in the previous year. Age was also significant when expressed as a microbial maturity score (Spearman Rho, 0.39; P  = 4.6 × 10 -10 ); however, this score was not associated with asthma/wheeze severity. Conclusions: There was a modest difference in the oropharyngeal airway microbiota between children with severe and mild/moderate asthma/wheeze across all children but not in individual age groups, and a strong association between the microbiota and age. This suggests the oropharyngeal airway microbiota as an interesting entity in studying asthma severity, but probably without the strength to serve as a biomarker for targeted intervention.
Databáze: MEDLINE