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

Purpose: Inspiring high partial pressure of oxygen (FiO > 0.6) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (POT). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect POT prior to the onset of clinical symptoms.

Methods: Male Yorkshire swine (20-30 kg) were placed into custom airtight runs and randomized to air (0.209 FiO, = 12) or oxygen (>0.95 FiO, = 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.

Results: Swine exposed to hyperoxia developed pulmonary injury consistent with POT. 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/FiO 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 POT with a ROC/AUC curve of 0.72 defined as a of PaO/FiO ratio less than 350 mmHg.

Conclusion: Exposing swine to 72 h of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of POT. VOC analysis identified six VOCs in exhaled breath that preceded POT. 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.