A meta-analysis of normal human blood cholinesterase activities determined by a modified electrometric method

Abstract

Measurements of blood cholinesterase (ChE) activities, including those of erythrocytes (EChE), plasma or serum (PChE), and whole blood (WBChE), are used to assess exposure to ChE-inhibiting pesticides. The purpose of this review was to report normal reference ChE activities in the blood of healthy adult humans, as determined by a modified electrometric method. We performed a systematic review following PRISMA guidelines. Single-group meta-analysis of means of PChE, EChE, and WBChE activities of adult healthy subjects was conducted using the random effects model. The programs used were Open-Meta Analyst and Meta-Essentials Version 1.5. Studies selected for analysis comprised 21, 19, and 4 reports of normal reference/baseline PChE, EChE, and WBChE activities in 690, 635, and 121 healthy adult males and/or females, respectively. The meta-analysis showed normal reference values of the means (effect sizes) with 95% CI of PChE, EChE, and WBChE activities of healthy adult subjects, which were 1.078 (1.015, 1.142), 1.075 (1.024, 1.125) and 1.331 (1.226, 1.436), respectively. By the subgroup analysis, heterogeneity (I2>89%) was considerably reduced in females to 4.4% and 30.1% for PChE and EChE, respectively. Funnel plots indicated no publication bias. However, Egger's regression confirmed the symmetry of the data points for PChE and WBChE activities with a significant effect on EChE. This meta-analysis showed normal reference values of PChE, EChE, and WBChE activities, measured by a modified electrometric method, in healthy adult humans.

Keywords: acetylcholinesterase; biomonitoring; carbamates; meta-analysis; organophosphates; pesticides.

Figure 1

PRISMA flow diagram for systematic review of studies including searches of databases and other sources reporting reference/baseline blood cholinesterase (ChE) values in healthy adult human subjects.

Figure 2

The forest plot and cumulative meta-analysis of cholinesterase activities (Δ pH/20 min) in the plasma (A – PChE), erythrocytes (B – EChE) and whole blood (C – WBChE) reported in healthy adult subjects by various studies using the modified electrometric method.

Figure 3

The forest plot of one-report leave-out sensitivity analysis of cholinesterase activities (Δ pH/20 min) in the plasma (A – PChE), erythrocytes (B – EChE) and whole blood (C – WBChE) reported in healthy adult subjects by various studies using the modified electrometric method.

Figure 4

The funnel plot (publication bias) cholinesterase activities (Δ pH/20 min) in the plasma (A – PChE), erythrocytes (B – EChE) and whole blood (C – WBChE) in healthy adult subjects reported by various studies using the modified electrometric method. X-axis represents the mean cholinesterase activity (effect size) and the Y-axis represents the standard error of the mean. The trim-and-fill analysis was also included by the imputed data points (open circles) for the adjustment of potentially missing studies in PChE and EChE.

Figure 4

The funnel plot (publication bias) cholinesterase activities (Δ pH/20 min) in the plasma (A – PChE), erythrocytes (B – EChE) and whole blood (C – WBChE) in healthy adult subjects reported by various studies using the modified electrometric method. X-axis represents the mean cholinesterase activity (effect size) and the Y-axis represents the standard error of the mean. The trim-and-fill analysis was also included by the imputed data points (open circles) for the adjustment of potentially missing studies in PChE and EChE.