TY - JOUR

T1 - Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents

AU - Thorsen, Jonathan

AU - Stokholm, Jakob

AU - Rasmussen, Morten Arendt

AU - Roggenbuck-Wedemeyer, Michael

AU - Vissing, Nadja H.

AU - Mortensen, Martin S.

AU - Brejnrod, Asker D.

AU - Fleming, Louise

AU - Bush, Andrew

AU - Roberts, Graham

AU - Singer, Florian

AU - Frey, Urs

AU - Hedlin, Gunilla

AU - Nordlund, Björn

AU - Murray, Clare S.

AU - Abdel-Aziz, Mahmoud I.

AU - Hashimoto, Simone

AU - van Aalderen, Wim

AU - Maitland-van der Zee, Anke H.

AU - Shaw, Dominick

AU - Fowler, Stephen J.

AU - Sousa, Ana

AU - Sterk, Peter J.

AU - Chung, Kian Fan

AU - Adcock, Ian M.

AU - Djukanovic, Ratko

AU - Auffray, Charles

AU - Bansal, Aruna T.

AU - Wagers, Scott

AU - Chawes, Bo

AU - Bønnelykke, Klaus

AU - Sørensen, Søren Johannes

AU - Bisgaard, Hans

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - airway

KW - microbiota

KW - oropharyngeal

KW - pediatrics

KW - severe asthma

U2 - 10.1513/AnnalsATS.202110-1152OC

DO - 10.1513/AnnalsATS.202110-1152OC

M3 - Journal article

C2 - 35904980

AN - SCOPUS:85143197291

VL - 19

SP - 2031

EP - 2043

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

SN - 2325-6621

IS - 12

ER -