Early detection and identification of ventilator associated pneumonia

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ABSTRACT: Ventilator associated pneumonias (VAP) are a common complication in mechanically ventilated patients, occurring more than 250,000 times annually. VAPs occur in a high percentage of mechanically ventilated patients with acute respiratory distress syndrome (ARDS, 29%) and COVID-19 (>50%). Timely detection and identification of the pathogen is key to effective treatment, as is differentiating colonization from acute infection. The most common options for microbiological diagnosis are cultures of endotracheal aspirate or bronchoalveolar lavage. Sampling aspirate is non-invasive, but the samples are prone to contamination from the proximal airways. Bronchoalveolar lavage (BAL) allows for sample collection from the distal lung without proximal airway contamination, but this technique is invasive and cannot be repeated frequently for surveillance. Here we propose to develop and test a non-invasive, high-efficiency system for collecting exhaled respiratory aerosols from mechanically ventilated patients. This system will collect large aerosols, typically generated in the proximal airways, separately from smaller aerosols, which are typically generated in the very distal airways, thus providing independent samples from these two distinct compartments of the lung. The collection of a sample from the distal lung will facilitate the correct diagnosis VAP. The system will allow for short sample collection times, facilitating repeated measures and timely surveillance, and will be developed and tested in an ex vivo human lung model using culture and non-culture-based methods. We will also evaluate the utility of collected aerosol samples for surveying the microbial, fungal, and viral community members in the lung (the lung microbiome). Misbalances in the bacterial communities (respiratory dysbiosis) have been associated with decreased survival in mechanically ventilated patients and may play a role in both local and systemic inflammation. Finally, we will evaluate the use of exhaled aerosol samples to indicate host response to infection and lung injury through the analysis of biomarkers related to endothelial and epithelial permeability, inflammation, and infection. Markers of host response and lung injury may help to differentiate simple bacterial colonization from acute infection and VAP. Pneumonia is the leading cause of Acute Respiratory Distress Syndrome (ARDS), an often-lethal complication involving a complex dysregulated inflammatory response that causes loss of endothelial and epithelial barrier integrity, resulting in pulmonary edema and respiratory failure. Serial biomarker measurements from distal lung samples may also elucidate the etiology of ARDS after lung infection.