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

Matthew J Martin,Glenn Hearson,Ben Forbes,Graham Rose,Nur Masirah M Zain,David J Wooldridge,Tim W Harrison,Saheer E Gharbia,Garrit Koller,Damian W Rivett,Kenneth D Bruce

doi:10.1371/journal.pone.0244681

Matthew J Martin, Glenn Hearson + Show 9 more

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https://doi.org/10.1371/journal.pone.0244681

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Abstract

BackgroundInhaled 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.MethodsWe 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.ResultsA 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.DiscussionWhilst 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 registrationClinicalTrials.gov NCT02671773

Highlights

Asthma is a common cause of morbidity and mortality affecting an estimated 334 million individuals worldwide [1, 2]
No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose Inhaled corticosteroids (ICS) groups
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

Summary

Introduction

Asthma is a common cause of morbidity and mortality affecting an estimated 334 million individuals worldwide [1, 2]. The key initial step towards a better understanding is characterising the abundance and diversity of bacteria in the asthmatic airways This is possible due to techniques that characterise microbiome composition. The most common genera across many microbiome studies of the asthmatic airways are Prevotella, Veillonella, Haemophilus, Streptococcus and Moraxella [12,13,14,15] Some of these genera contain potential pathogens which are common causes of pneumonia, such as Haemophilus and Streptococcus spp. and both of these species have been detected at higher frequencies in poorly controlled asthmatics and subjects with treatment-resistant severe asthma [12, 14,15,16]. 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

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