Study Suggests Alternative Method of Diagnosing Lung Infection

As ventilator use in hospitals skyrockets during the COVID-19 pandemic, results of a study by the Translational Genomics Research Institute (TGen), City of Hope, HonorHealth Research and Innovation Institute, and the University of Arizona College of Medicine – Phoenix suggests there may be a better way to diagnose ventilator-associated pneumonia (VAP).

The findings of this study, which was supervised by Patrick Pirrotte, PhD, director of TGen’s Collaborative Center for Translational Mass Spectrometry and a research assistant professor in the Department of Basic Medical Sciences, were published today in the scientific journal Molecular & Cellular Proteomics.

Intensive care unit (ICU) patients with prolonged hospitalizations, and in need of a mechanical device to help them breathe, are at high risk for developing VAP, which can increase the length and cost of hospital stays by as much as $50,000 per patient. VAP is associated with 60 percent of all hospital-acquired infections. VAP is also associated with more than half of ICU antibiotic use, which can lead to multi-drug resistance.

Currently, the most common way of diagnosing VAP and guiding treatment options is through the use of bronchoalveolar lavage (BAL), in which an invasive bronchoscope is passed through the mouth or nose deep into the patient’s airway and lungs, with a measured amount of fluid introduced and then collected for examination.

The TGen-led research team assessed an alternative method called endotracheal aspirates (ETA), a non-invasive, faster and less costly diagnostic test in which respiratory secretions are suctioned from the lungs of patients using the already inserted intubation tube. This study represents the first detailed characterization of ETA proteins and metabolites.

“ETA has been historically overlooked in favor of BAL,” said Khyati Pathak, PhD, a staff scientist in TGen’s Collaborative Center for Translational Mass Spectrometry, and one of the study’s lead authors.

Marissa McGilvrey, a research associate in Dr. Pirrotte’s lab, and one of the study’s lead authors, agrees: “Our study revealed that ETA is functionally diverse and highly enriched in proteins involved in immunity, suggesting that ETA is an attractive source to study lung infection.”

The study involved 16 patients under mechanical ventilation in the ICU trauma center at HonorHealth Scottsdale Osborn Medical Center. Eleven of the patients acquired VAP.

“Intubation is one of the most common interventions in critical care and has been linked to increased susceptibility of lung infection and death,” said Charles Hu, MD, a Phoenix-area trauma and critical care surgeon, and an author of the study. “Intubation procedure, duration on the ventilator, length of stay and inappropriate antibiotic treatment, as well as compromised or weakened immunity, may contribute to the development of pneumonia.”

ETA Provides More Frequent ‘Molecular Snapshots’

One of the advantages of ETA is that it can easily be done repeatedly without invasive procedure. ETA was collected daily, starting at the first day of intubation. BAL was collected as part of current standard-of-care procedures and used for microbial cultures to aid in clinical diagnosis.

“We hypothesized that reduced invasiveness involved in ETA sampling allows easier and more frequent molecular snapshots of the patient immune response,” said Frederic Zenhausern, PhD, MBA, director of the Center for Applied NanoBioscience and Medicine at the University of Arizona College of Medicine – Phoenix, and one of the study authors. He also holds appointments at TGen and HonorHealth. “We anticipated that this enhanced granularity would provide valuable mechanistic insights into the causes of VAP.”

Researches showed that ETA captures a rich and diverse airway proteome, enabling detection of VAP pathogen peptides and immune proteins associated with an early response to infection.

“In the majority of VAP patients, these distinctive pathogen signatures found through ETA were present up to two days earlier than the BAL culture-based diagnosis,” said Dr. Pirrotte, the study’s senior author. “ETA may be an attractive alternative for earlier and cost-effective clinical diagnosis of pneumonia in intubated patients.”

This study — Molecular profiling of innate immune response mechanisms in ventilator-associated pneumonia — was funded by the Flinn Foundation and TGen. HonorHealth Research and Innovation Institute trauma research at Scottsdale Osborn Medical Center enrolled patients and collected data. City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, provided statistical analysis and reviewed data interpretation.

Story By: Steve Yozwiak, TGen Senior Science Writer

This story originally appeared on TGen's website.