Carbon monoxide (CO) is the leading agent of injury and death by poisoning worldwide. Diagnosis of CO poisoning can be delayed by non-specific symptoms, thus preventing early treatment and identification of the contamination source. Survivors are faced with potential impairments to cardiac and neurological function. Neurological sequelae are the most frequent form of morbidity, and dysfunction may occur acutely or arise in a delayed fashion. While acute abnormalities develop in a minority of severely poisoned patients, delayed neurological changes develop in 23-46 % of patients up to ~5 weeks after poisoning. Clinical reviews have expressed the urgent need for objective biomarkers of serious CO poisoning to select patients who may benefit from aggressive treatment. The formation of carboxy-hemoglobin (COHb) is a recognized effect of CO exposure; however, COHb values correlate poorly with clinical outcomes. Even when CO poisoning appears to be relatively mild, delayed neurological sequelae can still occur. A number of research groups are performing detailed studies to evaluate the expression of individual biomarkers associated with CO poisoning for use as a diagnostic tool. However, the standard method for measuring plasma or serum levels of cytokines, chemokines or other biomarkers is to measure them one at a time using Enzyme-Linked Immunosorbent Assay. One-at-a- time assessment of each putative biomarker incurs considerable time, cost and sample volume. Clearly, no single molecular marker, or small group of markers, will be able to accurately classify individuals at highest risk. The ability to systematically identify protein profiles, predict risk of clinical events, evaluate therapeutic response, and define underlying mechanisms is thereby limited severely. Rules-Based Medicine has developed Multi-Analyte Profiles (MAPs) to screen large numbers of biomarkers in parallel, using bead-based multiplex immunoassays. This technology provides a quantitative evaluation of protein expression patterns using very small sample volumes (10-20

Public Health Relevance

Carbon monoxide (CO) is the leading agent of injury and death by poisoning worldwide. Unfortunately, current diagnosis using carboxy-hemoglobin (COHb) values correlate poorly with clinical outcomes. The identification of novel biomarker patterns of individuals with CO poisoning, as well as, individuals at high risk for developing neurological dysfunction and morbidity, will allow for improved management of the condition by selecting objectively patients who may benefit from aggressive treatment, aiding the determination of treatment effectiveness, defining underlying mechanisms, and will provide a framework for developing and evaluating new treatments. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43ES016720-01
Application #
7483410
Study Section
Special Emphasis Panel (ZRG1-BDCN-A (11))
Program Officer
Heindel, Jerrold
Project Start
2008-05-01
Project End
2008-10-31
Budget Start
2008-05-01
Budget End
2008-10-31
Support Year
1
Fiscal Year
2008
Total Cost
$100,000
Indirect Cost
Name
Rules-Based Medicine, Inc.
Department
Type
DUNS #
114417327
City
Austin
State
TX
Country
United States
Zip Code
78759
Thom, Stephen R; Bhopale, Veena M; Milovanova, Tatyana M et al. (2010) Plasma biomarkers in carbon monoxide poisoning. Clin Toxicol (Phila) 48:47-56