Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents
Jonathan Thorsen, Jakob Stokholm, Morten Arendt Rasmussen, Michael Roggenbuck-Wedemeyer, Nadja Hawwa Vissing, Martin Steen Mortensen, Asker Brejnrod, Louise Fleming, Andrew Bush, Graham Roberts, Florian Singer, Urs Frey, Gunilla Hedlin, Björn Nordlund, Clare Murray, Mahmoud I. Abdel‐Aziz, Simone Hashimoto, Wim van Aalderen, Anke H. Maitland‐van der Zee, Dominick Shaw, Stephen J. Fowler, Ana Sousa, Peter J. Sterk, Kian Fan Chung, Ian M. Adcock, Ratko Djukanović, Charles Auffray, Aruna T. Bansal, Scott Wagers, Bo Chawes, Klaus Bønnelykke, Søren J. Sørensen, Hans Bisgaard
Abstract
Abstract 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.