Airway microbiota ‘unlikely to be a strong target’ in severe childhood asthma/wheeze

Children with asthma/wheeze demonstrated a strong relationship between age and airway microbiota, with a modest difference observed based on asthma severity, according to study results published in Annals of the American Thoracic Society.

Jonathan Thorsen

“Little is still known about the airway microbiome in children,” Jonathan Thorsen, MD, PhD, senior researcher for Copenhagen Prospective Studies on Asthma in Childhood, told Healio. “We were excited to see such a strong association between the airway microbiota and the age of the children — this highlights both a biologically interesting phenomenon but also the importance of accounting for the age of participants in future studies or microbiome-based clinical applications.”

In a European multicenter study, Thorsen and colleagues assessed 241 oropharyngeal swab samples from children and adolescents with severe and mild/moderate asthma or wheeze from the U-BIOPRED (Unbiased BIOmarkers in the PREDiction of respiratory disease outcomes) study to observe any differences between their airway microbiotas.

“The present study is a part of the wonderful U-BIOPRED consortium project, which is a unique multidisciplinary effort to better understand severe asthma and improve the lives of the patients, both children and adults, who suffer from the disease,” Thorsen told Healio. “Alongside this study, we are working to understand the developing microbiome in children before the onset of asthma, which may lead to better disease prediction and even prevention.”

Of the total cohort, 86 school-age children had severe asthma, 39 school-age children had mild/moderate asthma, 65 preschool children had severe wheeze and 51 preschool children had mild/moderate wheeze.

Researchers used 16S ribosomal RNA gene sequencing to analyze the samples, most frequently identifying Streptococcus (mean relative abundance, 33.5%), Veillonella (10.3%), Haemophilus (7%), Prevotella (5.9%) and Rothia (5.5%).

Using the F statistic, or the between-group vs. within-group variance, to measure effect size, researchers found a strong relationship between age group of the children and the microbiota in beta-diversity analysis (F = 3.32; P = .011).

A differential abundance analysis between age groups also showed 28 significant amplicon sequence variants (P < .05), with Megasphaera micronuciformis, Actinomyces graevenitzii, Veillonella and Prevotella most common in school-age group, and Alloprevotella, Porphyromonas, Neisseria and an unknown bacterial taxon most common in the preschool group. Also, microbial maturity score, derived from the random forest model of amplicon sequence variants, appeared significantly associated with age (Spearman’s rho, 0.39; P = 4.6 x 10^–10), according to researchers.

In univariable beta-diversity analysis, microbiota between those with severe and mild/moderate asthma or wheeze did not significantly differ for the total cohort (F = 1.99), nor for each age group (school-age, F = 0.64; preschool, F = 1.08).

When using a multivariable model, however, researchers did find a significant difference in asthma/wheeze severity for all children (F = 2.66; P = .035). However, this significance was not found separately in the preschool or school-age groups. This model also showed a stronger relationship between microbiota and number of exacerbations in the year prior (F = 4.98; P = .001). No single bacterial amplicon sequence variants were different between those with severe and mild/moderate asthma or wheeze.

“There’s an important focus on improving the treatment for children with severe asthma, and hence a need for biomarkers and new types of therapy,” Thorsen said. “However, we did not find a strong association between the airway microbiome and asthma severity, indicating that it’s unlikely to be a strong target for new treatments by itself.”

“We are currently working to expand the study with multiple other readouts from molecular biology methods (‘omics’) to characterize how these bacteria interact with the child, which may lead to new insights,” Thorsen told Healio.

For more information:

Jonathan Thorsen, MD, PhD, can be reached at [email protected].

Headshot credit: Brian Vegas