Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026
Parallel metagenomic- and culture-based approaches show nasal swabs are a good proxy for broncho-alveolar lavage in children with cystic fibrosis.
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FitzGerald Jamie A, Lester Karen L, O' Sullivan Niamh, Crispie Fiona, Lawton Elaine M, Cotter Paul D, McNally Paul, Cox Des W
Аннотация
BACKGROUND: Broncho-Alveolar Lavage (BAL) is the reference standard for airway surveillance in clinical management of cystic fibrosis (CF), but is invasive and requires general anaesthesia in children. Non-invasive alternatives can lack specificity (Oropharyngeal swabs; OPS), or evaluation in paediatric CF (Middle meatus sampling; MMS). We sought to determine if MMS via nasal-swabs performed better than OPS at representing the microbiological attributes of BAL.
METHODS: In a stable preschool CF cohort attending a single specialist centre, we evaluated the microbiological yield of BAL, MMS, and OPS sampling using both standard clinical culturing, and shotgun metagenomic sequencing (Illumina NextSeq 500).
RESULTS: Matched BAL, MMS, and OPS from 30 preschool children provided 88 samples. While both culture and metagenomic surveillance performed well at detecting S. pneumoniae in BAL, MMS performed better at detecting S. aureus, M. catarrhalis and Escherichia coli, while OPS performed better at detecting H. Influenzae. Metagenomics revealed a significantly more diverse microbiome in OPS than BAL or MMS. While agreement on pathogen profiles varied widely between metagenomics and culture methods, MMS more accurately represented BAL, particularly for Streptococcus, M. catarrhalis, and Escherichia.
CONCLUSIONS: MMS and OPS cultures performed well as proxies for BAL in relation to certain pathogens. Metagenomics detected pathogens in many samples that were unobserved in culture, and showed the oropharynx microbiome to be much more diverse. Lung and nares microbiomes were more similar in composition and diversity. Our data suggest that nasal sampling of the middle meatus may be a more accurate surrogate for lower airway samples.
METHODS: In a stable preschool CF cohort attending a single specialist centre, we evaluated the microbiological yield of BAL, MMS, and OPS sampling using both standard clinical culturing, and shotgun metagenomic sequencing (Illumina NextSeq 500).
RESULTS: Matched BAL, MMS, and OPS from 30 preschool children provided 88 samples. While both culture and metagenomic surveillance performed well at detecting S. pneumoniae in BAL, MMS performed better at detecting S. aureus, M. catarrhalis and Escherichia coli, while OPS performed better at detecting H. Influenzae. Metagenomics revealed a significantly more diverse microbiome in OPS than BAL or MMS. While agreement on pathogen profiles varied widely between metagenomics and culture methods, MMS more accurately represented BAL, particularly for Streptococcus, M. catarrhalis, and Escherichia.
CONCLUSIONS: MMS and OPS cultures performed well as proxies for BAL in relation to certain pathogens. Metagenomics detected pathogens in many samples that were unobserved in culture, and showed the oropharynx microbiome to be much more diverse. Lung and nares microbiomes were more similar in composition and diversity. Our data suggest that nasal sampling of the middle meatus may be a more accurate surrogate for lower airway samples.