Skip to main content
Article
A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts
Frontiers in Neurology
  • Michael R. Miller, Lawson Health Research Institute
  • Alicia DiBattista, Children's Hospital of Eastern Ontario, Ottawa
  • Maitray A. Patel, Western University
  • Mark Daley, Western University
  • Catherine Tenn, Defence Research and Development Canada
  • Ann Nakashima, Defence Research and Development Canada
  • Shawn G. Rhind, Defence Research and Development Canada
  • Oshin Vartanian, Defence Research and Development Canada
  • Maria Y. Shiu, Defence Research and Development Canada
  • Norleen Caddy, Defence Research and Development Canada
  • Michelle Garrett, Defence Research and Development Canada
  • Doug Saunders, Defence Research and Development Canada
  • Ingrid Smith, Defence Research and Development Canada
  • Rakesh Jetly, National Defence and the Canadian Forces
  • Douglas D. Fraser, Lawson Health Research Institute
Document Type
Article
Publication Date
4-7-2022
URL with Digital Object Identifier
10.3389/fneur.2022.831792
Abstract

Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8–20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82–0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P < 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P < 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling.

Citation Information
Michael R. Miller, Alicia DiBattista, Maitray A. Patel, Mark Daley, et al.. "A Distinct Metabolite Signature in Military Personnel Exposed to Repetitive Low-Level Blasts" Frontiers in Neurology Vol. 13 (2022)
Available at: http://works.bepress.com/douglas-fraser/29/