AUTHOR=Cronin William A. , Forbes Angela S. , Wagner Kari L. , Kaplan Peter , Cataneo Renee , Phillips Michael , Mahon Richard , Hall Aaron 

TITLE=Exhaled Volatile Organic Compounds Precedes Pulmonary Injury in a Swine Pulmonary Oxygen Toxicity Model

JOURNAL=Frontiers in Physiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.01297

DOI=10.3389/fphys.2019.01297

ISSN=1664-042X

ABSTRACT=<sec><title>Purpose</title><p>Inspiring high partial pressure of oxygen (FiO<sub>2</sub> &gt; 0.6) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (PO<sub>2</sub>T). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO<sub>2</sub> levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect PO<sub>2</sub>T prior to the onset of clinical symptoms.</p></sec><sec><title>Methods</title><p>Male Yorkshire swine (20–30 kg) were placed into custom airtight runs and randomized to air (0.209 FiO<sub>2</sub>, <italic>n</italic> = 12) or oxygen (&gt;0.95 FiO<sub>2</sub>, <italic>n</italic> = 10) for 72 h. Breath samples, arterial blood gases, and vital signs were assessed every 12 h. After 72 h of exposure, animals were euthanized and the lungs processed for histology and wet-dry ratios.</p></sec><sec><title>Results</title><p>Swine exposed to hyperoxia developed pulmonary injury consistent with PO<sub>2</sub>T. Histology of oxygen-exposed swine showed pulmonary lymphatic congestion, epithelial sloughing, and neutrophil transmigration. Pulmonary injury was also evidenced by increased interstitial edema and a decreased PaO<sub>2</sub>/FiO<sub>2</sub> ratio in the oxygen group when compared to the air control group. Breath volatile organic compound (VOC) sample analysis identified six VOCs that were combined into an algorithm which generated a breath score predicting PO<sub>2</sub>T with a ROC/AUC curve of 0.72 defined as a of PaO<sub>2</sub>/FiO<sub>2</sub> ratio less than 350 mmHg.</p></sec><sec><title>Conclusion</title><p>Exposing swine to 72 h of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of PO<sub>2</sub>T. VOC analysis identified six VOCs in exhaled breath that preceded PO<sub>2</sub>T. Results show promise that a simple, non-invasive breath test could potentially predict the risk of pulmonary injury in humans exposed to high partial pressures of oxygen.</p></sec>