Nasopharyngeal microbiota in children is associated with severe asthma exacerbations

Gina J van Beveren; Wouter A A de Steenhuijsen Piters; Shelley A Boeschoten; Sam Louman; Mei Ling Chu; Kayleigh Arp; Pieter L Fraaij; Matthijs de Hoog; Corinne Buysse; Marlies A van Houten; Elisabeth A M Sanders; Peter J F M Merkus; Annemie L Boehmer; Debby Bogaert

doi:10.1016/j.jaci.2024.02.020

Nasopharyngeal microbiota in children is associated with severe asthma exacerbations

J Allergy Clin Immunol. 2024 Mar 10:S0091-6749(24)00239-2. doi: 10.1016/j.jaci.2024.02.020. Online ahead of print.

Authors

Affiliations

¹ Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Paediatrics, Spaarne Hospital, Haarlem, The Netherlands.
² Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
³ Department of Neonatal and Paediatric Intensive Care, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
⁴ Department of Paediatrics, Spaarne Hospital, Haarlem, The Netherlands.
⁵ Pediatric Infectious Diseases & Immunology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Viroscience, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
⁶ Division of Respiratory Medicine, Department of Paediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands.
⁷ Department of Paediatrics, Spaarne Hospital, Haarlem, The Netherlands; Department of Paediatrics, Maasstad Hospital, Rotterdam, The Netherlands.
⁸ Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: d.bogaert@ed.ac.uk.

PMID: 38467291
DOI: 10.1016/j.jaci.2024.02.020

Abstract

Background: The respiratory microbiome has been associated with the etiology and disease course of asthma.

Objective: We sought to assess the nasopharyngeal microbiota in children with a severe asthma exacerbation and their associations with medication, air quality, and viral infection.

Methods: A cross-sectional study was performed among children aged 2 to 18 years admitted to the medium care unit (MCU; n = 84) or intensive care unit (ICU; n = 78) with an asthma exacerbation. For case-control analyses, we matched all cases aged 2 to 6 years (n = 87) to controls in a 1:2 ratio. Controls were participants of either a prospective case-control study or a longitudinal birth cohort (n = 182). The nasopharyngeal microbiota was characterized by 16S-rRNA-gene sequencing.

Results: Cases showed higher Shannon diversity index (ICU and MCU combined; P = .002) and a distinct microbial community composition when compared with controls (permutational multivariate ANOVA R² = 1.9%; P < .001). We observed significantly higher abundance of Staphylococcus and "oral" taxa, including Neisseria, Veillonella, and Streptococcus spp. and a lower abundance of Dolosigranulum pigrum, Corynebacterium, and Moraxella spp. (MaAsLin2; q < 0.25) in cases versus controls. Furthermore, Neisseria abundance was associated with more severe disease (ICU vs MCU MaAslin2, P = .03; q = 0.30). Neisseria spp. abundance was also related with fine particulate matter exposure, whereas Haemophilus and Streptococcus abundances were related with recent inhaled corticosteroid use. We observed no correlations with viral infection.

Conclusions: Our results demonstrate that children admitted with asthma exacerbations harbor a microbiome characterized by overgrowth of Staphylococcus and "oral" microbes and an underrepresentation of beneficial niche-appropriate commensals. Several of these associations may be explained by (environmental or medical) exposures, although cause-consequence relationships remain unclear and require further investigations.

Keywords: Asthma; exacerbation; respiratory microbiome.