The airways microbiome of individuals with asthma treated with high and low doses of inhaled corticosteroids

PLoS One. 2020 Dec 30;15(12):e0244681. doi: 10.1371/journal.pone.0244681. eCollection 2020.

Abstract

Background: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. We assessed the composition of the asthmatic airways microbiome in asthma patients taking low and high dose ICS and the stability of the microbiome over a 2 week period.

Methods: We prospectively recruited 55 individuals with asthma. Of these, 22 were on low-dose ICS and 33 on high-dose ICS (16 on budesonide, 17 on fluticasone propionate). Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. 19 subjects returned for further sputum induction after 24 h and 2 weeks.

Results: A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups. However, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate than those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period.

Discussion: Whilst no significant differences were observed between the low- and high-dose ICS groups, increased abundance of the potential pathogen H. parainfluenzae was observed in patients taking high-dose fluticasone propionate compared to those taking high-dose budesonide. The microbiota were stable over fourteen days, providing novel evidence of the established community of bacteria in the asthmatic airways.

Clinical trial registration: ClinicalTrials.gov NCT02671773.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / microbiology*
  • Budesonide / administration & dosage
  • Budesonide / adverse effects
  • Budesonide / therapeutic use
  • Dose-Response Relationship, Drug
  • Fluticasone / administration & dosage
  • Fluticasone / adverse effects
  • Fluticasone / therapeutic use
  • Humans
  • Microbiota / drug effects*
  • Middle Aged
  • Prospective Studies
  • Respiratory Tract Infections / chemically induced*
  • Respiratory Tract Infections / microbiology
  • Sputum / microbiology*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Budesonide
  • Fluticasone

Associated data

  • ClinicalTrials.gov/NCT02671773

Grants and funding

This investigator-initiated study was funded by an unrestricted research grant from AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript