# Longitudinal analysis of respiratory tract microbiome change and sequence-based infection diagnosis during mechanical ventilation

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2020 · $195,696

## Abstract

PROJECT SUMMARY
Lower respiratory tract infection (LRTI) frequently contributes to respiratory failure that requires mechanical
ventilation, and ventilator-associated pneumonia is a feared complication in patients dependent upon
mechanical ventilation. Despite the clinical importance of LRTI in critical care, the dynamics of the respiratory
tract microbiome during mechanical ventilation that may correspond with risk for infection and the respiratory
tract microbiome features that define LRTI remain poorly understood. The proposed study will utilize deep
sequencing of the 16S rRNA gene from upper and lower respiratory tract samples obtained from critically ill,
mechanically ventilated subjects in order to improve understanding of healthcare-associated microbiome
change, LRTI microbial ecology, and LRTI pathogenesis. The study will (1) define the longitudinal change that
occurs in the upper and lower respiratory tract bacterial microbiome during mechanical ventilation; (2)
determine the features of respiratory tract microbiome community structure that correlate with the clinical
diagnosis of LRTI and with the absence of LRTI; and (3) evaluate the ability of 16S rRNA gene sequencing to
identify bacterial pathogens responsible for LRTI. Execution of these specific aims will elucidate the
relationships between healthcare exposures and respiratory tract microbiome change, and between respiratory
tract microbiome change and LRTI pathogenesis. The proposed study will thus form a foundation for an
independent career in patient-oriented research dedicated to improving understanding of healthcare-
associated microbiome change and infection. Execution of the aims will also provide the primary investigator
with essential experience directing a large, observational microbiome study and with essential training in the
advanced statistical and bioinformatics methods necessary to analyze the interaction between patient-level
factors (underlying disease, antibiotic exposure, etc), microbial ecology, and infection. The research proposal
is paired with a career development plan that makes use of the extensive resources of the University of
Pennsylvania, and which capitalizes on a mentorship committee with broad, complementary expertise in
infectious diseases epidemiology, healthcare-associated infection, deep sequencing methods, microbiology,
and critical care. Dr. Ebbing Lautenbach, Dr. Frederic D. Bushman, and Dr. Ronald G. Collman will support the
primary investigator in the outlined path towards a successful career as an independent clinical investigator.

## Key facts

- **NIH application ID:** 9930524
- **Project number:** 5K23AI121485-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Brendan Joseph Kelly
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,696
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930524

## Citation

> US National Institutes of Health, RePORTER application 9930524, Longitudinal analysis of respiratory tract microbiome change and sequence-based infection diagnosis during mechanical ventilation (5K23AI121485-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9930524. Licensed CC0.

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