Concordance between upper and lower airway microbiota in children with Cystic Fibrosis

Abstract

Background: Sputum is the sample to monitor the lower respiratory tract microbiota in cystic fibrosis (CF), but young patients often cannot expectorate. We hypothesized that throat swabs could reflect lower airway colonization and assessed the concordance of bacterial community composition between paired sputum and throat swab samples from children with CF. Methods: The prospective longitudinal multicenter MUCOVIB cohort included 379 samples from 61 CF children. Using V3-V4 16S rRNA amplicon metagenomics, we compared bacterial community diversity and composition between sputum and throat swabs in the full cohort and in 11 patients with paired samples from the same visit. Results: Sputum and Throat swabs exhibited similar bacterial diversity, regardless of the exacerbation status, and presented a substantial agreement for detecting pathogens (Cohen Kappa: 0.6). Differences in bacterial abundance were observed (p=0.001), but not presence/absence (p=0.098). Community typing revealed three distinct community types, with 86% of paired samples falling into the same cluster, highlighting the homogeneity between sputum and throat swabs microbiota. Network analysis demonstrated slight, non-random similarities in microbial interactions between sample types (ARI = 0.08 and 0.10). The average distance between samples collected from the same visit was shorter (0.505, +/-0.056 95%CI), compared to sputum (0.695, +/-0.017) or throat swab (0.704, +/-0.045) from the same patient collected during different visits. Conclusions: Throat swabs can provide representative information on lower respiratory microbiota. Clinicians should collect throat swabs rather than relying on sputum samples from previous visits to guide antibiotic prescriptions in CF children unable to expectorate.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

MUCOVIB study was supported by grants from the Leenaards and Santos-Suarez Foundations, Vifor, and Novartis pharmaceutical industries. This analysis was supported as part of NCCR Microbiomes, a National Centre of Competence in Research, funded by the Swiss National Science Foundation (grant number 180575). VS was supported by an SNSF Grant (number 10531C-170280, F. Taroni, L. Falquet, and G. Greub).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the "Commission cantonale d'ethique de la recherche sur l'etre humain" of Vaud (CER-VD) and Geneva (CCER-GE) number 158/15 and 15-157, respectively.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Raw 16S amplicon sequences are available in the European Nucleotide Archive (ENA) with project number PRJEB41059

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