The upper-airway microbiota and loss of asthma control among asthmatic children

Yanjiao Zhou,David Mauger,Mario Castro,George M Weinstock,Gregory A Storch,Homer Boushey,Leonard B Bacharier,Wanda Phipatanakul,Robert F Lemanske,Anne M Fitzpatrick,Avraham Beigelman,Rachel G Robison,Kristine Wylie,Daniel Jackson,Yvonne Huang,Juliana Durack,Ronina Covar

doi:10.1038/s41467-019-13698-x

Abstract

The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota’s dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium’s relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

Highlights

The airway microbiome has an important role in asthma pathophysiology
We prospectively investigate whether the upper-airway microbiota at the time of respiratory health is related to the development of future Yellow Zone (YZ) episodes, and whether the microbiome at YZ are related to the likelihood of progression to severe asthma exacerbation requiring oral corticosteroids (OCS)
The presence of a pet in the house was associated with an increased risk of developing YZ (OR = 2.8, 95% CI 1.5–5.4, p = 0.006; (Fig. 1c)). 22.9% of the participants were treated with antibiotics during the 6 months prior to randomization, but this covariate did not affect the composition of the microbiota at time of randomization (p = 0.52, PERMANOVA)

Summary

Introduction

The airway microbiome has an important role in asthma pathophysiology. little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. The airway microbiome is associated with respiratory illness severity, future wheezing, and childhood asthma[3–7]. It is unknown if the airway microbiome is related to asthma control and risk of exacerbations among school-age children with mild asthma. We prospectively investigate whether the upper-airway microbiota at the time of respiratory health (randomization) is related to the development of future YZ episodes, and whether the microbiome at YZ are related to the likelihood of progression to severe asthma exacerbation requiring oral corticosteroids (OCS). We report that the airway microbiota colonization patterns are differentially associated with risk of loss of asthma control and severe exacerbations. Airway microbiota dominated by Corynebacterium + Dolosigranulum genera are associated with favorable clinical outcomes compared to microbiota dominated by more pathogenic bacteria: Staphylococcus, Streptococcus, and Moraxella

Methods

Results

Conclusion