Exhaled Volatile Organic Compounds during Inflammation Induced by TNF-α in Ventilated Rats

Abstract

Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-α). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 each) with intravenous injections of normal saline (control), 200 µg·kg−1 bodyweight TNF-α (TNF-α-200), or 600 µg·kg−1 bodyweight TNF-α (TNF-α-600), and were observed for 24 h or until death. Animals were ventilated with highly-purified synthetic air to analyze exhaled air by multicapillary column–ion mobility spectrometry. Volatile organic compounds (VOCs) were identified from a database. We recorded blood pressure and cardiac output, along with cytokine plasma concentrations. Control rats survived the 24 h observation period, whereas mean survival time decreased to 22 h for TNF-α-200 and 23 h for TNF-α-600 rats. Mean arterial pressure decreased in TNF-α groups, whereas IL-6 increased, consistent with mild to moderate inflammation. Hundreds of VOCs were detected in exhalome. P-cymol increased by a factor-of-two 4 h after injection of TNF-α-600 compared to the control and TNF-α-200. We found that 1-butanol and 1-pentanol increased in both TNF-α groups after 20 h compared to the control. As breath analysis distinguishes between two doses of TNF-α and none, we conclude that it might help clinicians identify systemic inflammation.

Social determinants of health, the microbiome, and surgical injury

“…Another window to the possibility that microbial genes, pathways, and metabolites are interacting within the host to alter its immune response is the use of exhaled lung air, what some have termed a "gas lavage." [48][49][50] Use of multiple analytic technologies including multicapillary column-ion mobility spectrometry, thermal desorption-gas chromatography mass spectrometry, and others have been employed to detect both volatile and nonvolatile organic compounds that reflect both host tissue metabolism and microbial metabolism. [48][49][50] For example, indoles, metabolites produced exclusively by commensal and pathogenic microbes within the gut and lung, are known to bind to the aryl hydrocarbon receptor and activate macrophages, key immune cells that clear infection.…”

“…[48][49][50] Use of multiple analytic technologies including multicapillary column-ion mobility spectrometry, thermal desorption-gas chromatography mass spectrometry, and others have been employed to detect both volatile and nonvolatile organic compounds that reflect both host tissue metabolism and microbial metabolism. [48][49][50] For example, indoles, metabolites produced exclusively by commensal and pathogenic microbes within the gut and lung, are known to bind to the aryl hydrocarbon receptor and activate macrophages, key immune cells that clear infection. 51 Indoles can be directly detected in lung gas, expelled stool, and plasma.…”

The Impact of Short-Term Exposure to Air Pollution on the Exhaled Breath of Healthy Adults

“…Previous literature has shown that particulate matter has adverse health effects on the respiratory and cardiovascular system, in which fine and ultrafine particles (UFP) can induce pulmonary as well as systemic inflammation [ 5 , 6 , 7 , 8 ] and oxidative stress [ 9 , 10 ]. Such processes have been shown to be reflected in exhaled breath patterns of ventilated rats and patients with asthma or chronic obstructive pulmonary disease (COPD) [ 11 , 12 , 13 ]. Therefore, we hypothesize that exposure to air pollution could be detected in the exhaled breath profile.…”