# Microbiome-host interplay in viral respiratory infections: A tracheostomy cohort

> **NIH NIH R56** · BOSTON CHILDREN'S HOSPITAL · 2021 · $863,496

## Abstract

PROJECT SUMMARY / ABSTRACT
Children with tracheostomy and home ventilation have an annual mortality rate of 5%, and have the highest
healthcare utilization and costs of all U.S. children, with annual hospital charges that exceed $2.5 billion. ARIs
are the #1 cause of death and hospitalization in this very high-risk population of healthcare superutilizers. Yet,
little is known about the pathophysiology of these ARIs, the mechanisms underlying their severity, and no
treatment pathways exist. Our long term goal is to refine the “one pathogen-one disease” ARI paradigm to a
more ecosystem-wide approach to ARI pathobiology in order to develop more precise ARI treatment strategies
for this population. The overall objective of this study is to determine the interplay within the ecosystem (i.e.,
between airway microbiome and host response) in the severity of viral ARI. The rationale is that while most
ARIs are viral, viruses infect airways colonized with functional bacteria. In a previous tracheostomy study we
found blooms (i.e., increased relative abundance) of a colonizing bacterium during a viral ARI. However, it
remains unclear if these blooms represent infections requiring antibiotics or are associated with ARI severity.
Our cross-sectional results and those of others show children with dominance of specific microbiota
compositions are associated with increased viral ARI severity. We will now extend this work by applying
metatranscriptomic (microbial function) and transcriptomic (host response) approaches to tracheal aspirates
collected longitudinally over an 18 month period from children with tracheostomy and home ventilation. To
conduct this study, we propose a 10-center, prospective cohort of 300 children with a tracheostomy and home
ventilation, which would be the largest and most comprehensive study in this population to date. We will
conduct this study with the expertise of the Emergency Medicine Network (EMNet) and the support of the
Pediatric Acute Lung Injury & Sepsis Investigators (PALISI) network. Using tracheal aspirates collected ~1
week before and at the onset (i.e., day 1) of ARI, we plan to complete 3 Specific Aims. In Aim 1 we will
determine if specific bacterial blooms are related to higher viral ARI severity. In Aim 2 we will determine the
mechanisms underlying colonizing bacteria becoming pathogenic and how bacterial blooms contribute to viral
ARI severity. In Aim 3 we will determine if bacterial blooms are related to the airway host response and viral
ARI severity. Our pilot data demonstrate compelling support for our hypotheses. This study has >80% power
for all aims, validates the results in a generalizable independent cohort, and creates a robust biorepository
from multiple ecological environments for testing future hypotheses. Results from this study will provide
fundamental insights into ARI pathophysiology and the mechanisms underlying ARI severity including how the
airway microbiome relates to bacterial blooms and host res...

## Key facts

- **NIH application ID:** 10455151
- **Project number:** 1R56AI163013-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Jonathan M Mansbach
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $863,496
- **Award type:** 1
- **Project period:** 2021-08-11 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455151

## Citation

> US National Institutes of Health, RePORTER application 10455151, Microbiome-host interplay in viral respiratory infections: A tracheostomy cohort (1R56AI163013-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455151. Licensed CC0.

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