Article Text
Abstract
Background Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa. However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional ‘off-target’ effects beyond merely P. aeruginosa and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response.
Methods We drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome.
Results Forty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2–35.2) and forced expiratory volume in 1 (FEV1) second was 57% predicted (IQR 44–74). Nineteen patients were defined a priori as responders having no net decrease in FEV1 in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of Staphylococcus in pretherapy baseline samples.
Conclusions Our longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S—suggesting the sputum microbiome could be used to personalise therapy.
- cystic fibrosis
- bronchiectasis
- bacterial infection
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Supplementary materials
Supplementary Data
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Footnotes
Contributors All authors meet requirements for authorship having contributed significantly to the project. AH, CT and MDP designed the study. AH, CT and MDP collected clinical data. HR, RS and MDP collected patient samples. AH performed experiments and was responsible for data analysis. Sample processing and statistical analyses were performed by AH, NA, ILL, LR, DS, RS, MS and MDP. AH wrote the initial draft of the manuscript, and all authors contributed to its revision. MDP supervised the study and serves as guarantor of the work.
Funding This work was supported by a grant to MDP from CIHR (364568).
Competing interests MDP, HR and MS have received research support from CF Canada, CIHR and Gilead.
Patient consent for publication Not required.
Ethics approval All patients provide prospective consent for the collection and storage of sputum samples for research purposes as approved by the Calgary Health Region Ethics Board (REB15-0854).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data from this project are available at; https://www.ncbi.nlm.nih.gov/bioproject/662963