Viruses In Pneumonia “VIP” study: CMV (and other herpesviruses) reactivation in lung of patients with ventilator-associated pneumonia

Principal Investigators: Ajit Limaye, MD, Sid Kapnadak, MD and Michael Boeckh, MD

Study Design: Prospective natural history study

Sponsor: Investigator Initiated

Most patients with Acute Respiratory Distress Syndrome (ARDS) require mechanical ventilation. This breathing assistance can be prolonged and puts them at an additional risk of ventilator associated pneumonia. This is a prospective natural history study to assess the incidence and clinical associations of CMV reactivation and measures of lung inflammation/injury in bronchoalveolar lavage (BAL) specimens of patients who undergo bronchoscopy/BAL for suspected ventilator-associated pneumonia.

Background/ Purpose

Multiple prior studies and our preliminary data demonstrate that reactivation of herpesviruses (EBV, CMV, HSV) in blood is common in non-immunosuppressed critically-ill patients and is associated with worse outcomes. The lung is both a major reservoir and target organ for CMV, and local (lung) reactivation can occur in the absence of systemic reactivation, where CMV-mediated lung injury may underlie the association between CMV reactivation and worse outcomes in the ICU.

This study’s objective is to prospectively assess the incidence and clinical associations of CMV reactivation and measures of lung inflammation/injury in BAL specimens of patients who undergo bronchoscopy/BAL for suspected ventilator-associated pneumonia.

Study Design

This is a prospective natural history study of patients who undergo bronchoscopy/BAL for suspected ventilator-associated pneumonia (VAP).

The specimens and clinical data include:

  • Excess (leftover) BAL sample (3-5mLs needed). The separation occurs when the clinical sample is collected. Right after the clinical sample is collected, the RT collects excess BAL for research purposes and it gets sent down to the microbiology lab.

  • Leftovers plasma samples and single prospectively collected blood sample (RNA PAX gene tube) within 24hr of bronchoscopy

  • Clinical variables extracted from the medical record by the research team, including demographics, duration of mechanical ventilation, hospital course, mortality, and clinical outcomes.

The study will focus on:

  • Isolating cells from both the alveolar space of the lung as well as blood in critically ill patients on the ventilator. We will quantify and test the functionality of these cells.

  • Seeing if and how genetic changes affect the functionality of these cells. We hope by understanding how this genetic change influences cell function, and by focusing on inflammatory cells, we may uncover a mechanism that provides directed treatment of ARDS.

  • Performing viral tests on blood and BAL fluid for the presence of viral infection in addition to bacterial infection for if it will be associated with worse outcomes.

Status: This study has completed enrollment with more than 200 participants and is currently in the analysis phase.