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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01297

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

 William A. Cronin1, 2, Angela Forbes1,  Kari L. Wagner1, Peter Kaplan3, Renee Cataneo3, Michael Phillips3,  Richard Mahon2 and  Aaron A. Hall2*
  • 1Walter Reed National Military Medical Center, United States
  • 2Naval Medical Research Center, United States
  • 3Menssana Research (United States), United States

Purpose: Inspiring high partial pressure of oxygen (FiO2 > 60%) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (PO2T). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO2 levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect PO2T prior to the onset of clinical symptoms. Methods: Male Yorkshire swine (20-30 kg) were placed into custom airtight runs and randomized to air (20.9% FiO2, n=12) or oxygen (>95% FiO2, n=10) for 72 hours. Breath samples, arterial blood gases, and vital signs were assessed every 12 hours. After 72 hours 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 PO2T. 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 PaO2/FiO2 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 PO2T with a ROC/AUC curve of 0.72 defined as a decrement of PaO2/FiO2 ratio less than 350 mmHg. Conclusions: Exposing swine to 72 hours of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of PO2T. VOC analysis identified six VOCs in exhaled breath that preceded PO2T. 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.

Keywords: Pulmonary oxygen toxicity, Volatile Organic Compounds, Hyperoxia, Swine, prediction

Received: 05 Jun 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Cronin, Forbes, Wagner, Kaplan, Cataneo, Phillips, Mahon and Hall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Aaron A. Hall, Naval Medical Research Center, Silver Spring, Maryland, United States,