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

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

Molecular Accounting and Profiling of Human Respiratory Microbial Communities: Toward Precision Medicine by Targeting the Respiratory Microbiome for Disease Diagnosis and Treatment

“…Despite the fact that treatment with omalizumab reduced exacerbations, the pathogenic nasal airway microbiota did not change significantly after treatment [ 170 ]. Furthermore, no significant variations in sputum bacterial load or overall community composition were found between low- and high-dose ICS treatment of asthmatic patients, according to Martin et al However, they discovered a link between high-dose fluticasone propionate and an increase in the pathogen Haemophilus parainfluenzae [ 171 ].…”

Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation

“…An additional, established role of FeNO measurement is to identify non‐adherence to inhaled corticosteroids 41,42 . Given the reported effects of inhaled steroids on airway ecology, 43–45 it is plausible that the lower proportions of Proteobacteria and low rates of viral infection observed in our high FeNO subgroup relate to a lower airway corticosteroid burden, despite similar reported doses across the subgroups. Direct, objective measures of inhaled corticosteroid load in individual subjects, such as via serum 46 or breath 47 monitoring, would facilitate further exploration of this in future trials.…”

Microbiome Research and Multi-Omics Integration for Personalized Medicine in Asthma

“…In addition, Martin et al could not identify significant differences in sputum bacterial load or overall community composition between low-and high-dose ICS treatment of asthmatic patients. However, they observed an association between high-dose fluticasone propionate and increased abundance of the pathogen Haemophilus parainfluenzae [166].…”