Identification of a marker of infection in the breath using a porcine pneumonia model

Abstract

ObjectivePneumonia, both in the community and the hospital setting, represents a significant cause of morbidity and mortality in the cardiothoracic patient population. Diagnosis of pneumonia can be masked by other disease processes and is often diagnosed after the patient is already experiencing the disease. A noninvasive, sensitive test for pneumonia could decrease hospitalizations and length of stay for patients. We have developed a porcine model of pneumonia and evaluated the exhaled breath of infected pigs for biomarkers of infection. MethodsAnesthetized 60-kg adult pigs were intubated, and a bronchoscope was used to instill a solution containing 12 × 108 cfu of methicillin-sensitive Staphylococcus aureus or a control solution without bacteria (Sham) into the distal airways. The pigs were then reintubated on postoperative days 3, 6, and 9, with bronchoscopic bronchial lavages taken at each time point. At each time point, a 500-mL breath was captured from each pig. The breath was evacuated over a silicon microchip, with the volatile carbonyl compounds from the breath captured via oximation reaction, and the results of this capture were analyzed by ultra-high performance liquid chromatography mass spectrometry. ResultsA total of 64% of the pigs inoculated with methicillin-sensitive S. aureus demonstrated consolidation on chest radiography and increasing counts of methicillin-sensitive S. aureus in the bronchial lavages over the span of the experiment, consistent with development of pneumonia. Analysis of the exhaled breath demonstrated 1 carbonyl compound (2-pentenal) that increased 10-fold over the span of the experiment, from an average of 0.0294 nmol/L before infection to an average of 0.3836 nmol/L on postoperative day 9. The amount of 2-pentenal present was greater in the breath of infected pigs than in the noninfected pigs or the sham inoculated pigs at postoperative days 6 and 9. Using an elevated concentration of 2-pentenal as a marker of infection yielded a sensitivity of 88% and specificity of 92% at postoperative day 6, and a sensitivity and specificity of 100% at postoperative day 9. ConclusionsWe were able to successfully develop a clinical pneumonia in adult 60-kg pigs. The concentration of 2-pentenal correlated with the presence of pneumonia, demonstrating the potential for this compound to function as a biomarker for methicillin-sensitive S. aureus infection in pigs.