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Metagenomic Sequencing and Evaluation of the Host Response in the Pediatric Aerodigestive Population
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  • Chelsea Gatcliffe,
  • Aparna Rao,
  • Matthew Brigger,
  • David Dimmock,
  • Christian Hansen,
  • Jesse Montgomery,
  • Robert Schlaberg,
  • Nicole Coufal,
  • Lauge Farnaes
Chelsea Gatcliffe
University of California San Diego
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Aparna Rao
University of California San Diego
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Matthew Brigger
University of California San Diego
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David Dimmock
Rady Children's Hospital San Diego
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Christian Hansen
Rady Children's Hospital San Diego
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Jesse Montgomery
IDbyDNA Inc.
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Robert Schlaberg
IDbyDNA Inc.
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Nicole Coufal
Rady Children's Hospital San Diego
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Lauge Farnaes
Rady Children's Hospital San Diego
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Abstract

Objectives To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. Clinical metagenomics allows for evaluation of both the respiratory microbiota and the transcriptome of the host immune response. Study Design and Methods Twenty-four children referred to an aerodigestive clinic were enrolled in a prospective, single-site, cross-sectional cohort study. At the time of clinical evaluation under anesthesia, two additional samples were obtained: an upper airway sample and a sample from bronchoalveolar lavage (BAL). Samples were sent for routine culture and analyzed using Explify® Respiratory, a CLIA Laboratory Developed Test (LDT) which identifies respiratory commensals and pathogens through RNA and DNA sequencing. Incidentally obtained host transcriptomics were analyzed to evaluate the host immune response. The results of these studies were correlated with the clinical presentation of the research subjects. Results In ten patients, organisms primarily associated with oral flora were identified in the BAL. Standard culture was negative in three patients where clinical metagenomics led to a result with potential clinical significance. Transcriptomic data correlated with the presence or absence of dysphagia as identified on prior videofluoroscopic evaluation of swallowing. Differentially expressed genes included upregulation of genes involved in the immune response, such as CXCL8 (interleukin 8) and ITGB2 (CD18). Conclusions Clinical metagenomics allows for simultaneous analysis of the microbiota and the host immune response from BAL samples. As the technologies in this field continue to advance, such testing may improve the diagnostic evaluation of patients with suspected chronic aspiration.

Peer review status:IN REVISION

01 Jun 2020Submitted to Pediatric Pulmonology
02 Jun 2020Submission Checks Completed
02 Jun 2020Assigned to Editor
13 Jun 2020Reviewer(s) Assigned
20 Jul 2020Review(s) Completed, Editorial Evaluation Pending
20 Jul 2020Editorial Decision: Revise Major
08 Sep 20201st Revision Received
18 Sep 2020Assigned to Editor
18 Sep 2020Reviewer(s) Assigned
18 Sep 2020Submission Checks Completed