Effect of influenza vaccination on oxidative stress products in breath

Abstract

Viral infections cause increased oxidative stress, so a breath test for oxidative stress biomarkers (alkanes and alkane derivatives) might provide a new tool for early diagnosis. We studied 33 normal healthy human subjects receiving scheduled treatment with live attenuated influenza vaccine (LAIV). Each subject was his or her own control, since they were studied on day 0 prior to vaccination, and then on days 2, 7 and 14 following vaccination. Breath volatile organic compounds (VOCs) were collected with a breath collection apparatus, then analyzed by automated thermal desorption with gas chromatography and mass spectroscopy. A Monte Carlo simulation technique identified non-random VOC biomarkers of infection based on their C-statistic values (area under curve of receiver operating characteristic). Treatment with LAIV was followed by non-random changes in the abundance of breath VOCs. 2, 8-Dimethylundecane and other alkane derivatives were observed on all days. Conservative multivariate models identified vaccinated subjects on day 2 (C-statistic = 0.82, sensitivity = 63.6% and specificity = 88.5%); day 7 (C-statistic = 0.94, sensitivity = 88.5% and specificity = 92.3%); and day 14 (C-statistic = 0.95, sensitivity = 92.3% and specificity = 92.3%). The altered breath VOCs were not detected in live attenuated influenza vaccine, excluding artifactual contamination. LAIV vaccination in healthy humans elicited a prompt and sustained increase in breath biomarkers of oxidative stress. A breath test for these VOCs could potentially identify humans who are acutely infected with influenza, but who have not yet developed clinical symptoms or signs of disease.

Volatile emanations fromin vitroairway cells infected with human rhinovirus

“…Even though some of the compounds are not identified unambiguously, it is clear that the majority of the detected compounds are long chain/branched aliphatic compounds, predominantly alkanes/alkenes and alcohols. These compounds—specifically alkanes and methylated alkanes—were previously reported as biomarkers of live attenuated influenza viral vaccination in breath (Phillips et al, 2003a, Phillips et al, 2003b, Phillips et al, 2000, Phillips et al, 2010) and they are also produced in a single cell culture (B cells) when infected with influenza A virus (Aksenov et al, 2014, in press). The production of these compounds is linked to oxidative stress during the infection (Schwarz, 1996) due to peroxidative cleavage of lipids (Phillips et al, 2000).…”

“…Aksenov et al described VOC profile changes of human B-cell leukocytes after infection with multiple influenza virus strains and found production of VOCs associated with oxidative stress (Aksenov et al, 2014, in press). Earlier clinical studies found a subset of these VOCs in exhaled breath of patients treated with live attenuated influenza vaccine (Phillips et al, 2010), although the detailed mechanisms by which these VOCs are produced remains unclear. HRV is thought to initially trigger inflammatory effects via recognition by the epithelial pattern recognition receptor TLR3 during active replication (Wang et al, 2009, Zhu et al, 2009).…”

A mobile instrumentation platform to distinguish airway disorders

“…For example, if the analytes of interest include aliphatic hydrocarbons, the 63 Ni source used in the present study would not efficiently ionizes these species. However, it has been reported that alkanes are highly relevant biomarkers indicative of oxidative stress associated with inflammation processes (Phillips et al, 2010). Further advancements may be achieved by modification of the carrier gas.…”

Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment

“…Immune responses can cause oxidative stress [Phillips et al, 2010;Slifka and Amanna, 2014]. If ATP is already deficient due to PMD or SMD prior to immune response and fever, neurologic regression could ensue after an immune response is triggered, when a certain 'threshold effect' is achieved.…”