Human red blood cell acetylcholinesterase activity: a revisit after fifteen years

Abstract

Human red blood cell acetylcholinesterase (RBC-AChE) activity is valuable for detecting potential exposure to cholinesterase inhibiting substances (CIS). A reliable population-based RBC-AChE activity reference range is critical for early and massive clinical and occupational toxicology screening. Previous published studies were often limited to small numbers of subjects, various testing methods, and crude statistical data analyses. We tested 4818 adult subjects with a well-established 17-minute modified Michel method over a 2-year period. We conducted a retrospective data analysis and systematically investigated on the influences to testing values from gender, age, age group, and their combinations and interactions. No significant difference was observed in the testing values between males (mean, medium, interquartile range = 0.76, 0.76, 0.71–0.80 ΔpH/h, respectively) and females (mean, medium, interquartile range = 0.76, 0.76, 0.71–0.81 ΔpH/hour, respectively), when gender was the only factor considered (p = 0.7238). However, with age progression, male testing values exhibited a consistent upward trend, while females did not show any clear patterns. Linear regression analysis of the data revealed that gender, age, and age group more or less affected testing values either as independent variables or with their combinations and interactions. However, more potential factors need to be included to achieve better testing value predictions. We recommend the toxicological testing community to adopt a new set of age group specific RBC-AChE activity reference ranges for males (0.68–0.80, 0.69–0.81, 0.70–0.83, 0.71–0.84, and 0.73–0.87 ΔpH/h for 18–29, 30–39, 40–49, 50–59, and ≥60 years old, respectively) while keeping the current reference range (0.63–0.89 ΔpH/hour) for females.

Keywords:

• Acetylcholinesterase activity clinical testing
• reference range
• chemical warfare nerve agent
• cholinesterase inhibiting substance
• organophosphate
• the Michel method

Acknowledgements

The authors would like to thank Lee J. Lefkowitz, Ph.D. (U.S. Army Evaluation Center) for important discussions, the Measures Team (Defense Health Agency) and Cristy Landt (BAMC Department of Clinical Investigation) for data analysis, and their colleagues at the DoD Cholinesterase Reference Laboratory, the DoD Food Analysis and Diagnostic Laboratory, and the U.S. Army Public Health Command, West for the support.

Disclaimer

The view(s) expressed herein are those of the authors and do not reflect the official policy or position of the U.S. Army Public Health Command, West (PHC, W), the U.S. Army Medical Department (AMEDD), the U.S. Army Office of the Surgeon General (USAOTSG), the Department of the Army (DA), the Department of Defense (DoD), or the U.S. Government.

Disclosure statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this paper.

Data availability statement

Raw data were generated at the CRL. Derived data supporting the findings of this study are available from the corresponding author [PK] on request.

Additional information

Funding

None declared.