Defining Reference Intervals of Emerging Extended Inflammatory Parameters (EIP) in a Population-Based Study

Extended inflammatory parameters (EIPs), including neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), reactive lymphocytes (RE-LYMP), and antibody-synthesizing lymphocytes (AS-LYMP), provide a rapid assessment of leukocyte activation. These parameters show diagnostic and prognostic value in infections and inflammatory diseases. However, their clinical application remains limited by the lack of standardized reference intervals (RIs), particularly in Southeast Asian populations. This study established population-based RIs for EIPs in healthy Thai adults.

Reference intervals were established following CLSI EP28-A3c guidelines. Healthy adults were included if they had no history of chronic disease, recent infection or inflammation, pregnancy, or medication use affecting white blood cells, and demonstrated normal CBC results without qualitative flags. Outliers were excluded using the Tukey method. Non-parametric methods were applied to calculate RIs, and the Harris and Boyd method was used to evaluate the need for age- and sex-specific partitioning.

Most EIPs did not require demographic partitioning. Reference intervals of NEUT-GI ranged from 146.7 to 160.0 scatter intensity (SI) units, and NEUT-RI ranged from 42.4 to 52.2 fluorescence intensity (FI) units. AS-LYMP% ranged from 0.0% to 0.4%, while AS-LYMP# ranged from 0.00 to 0.02 × 10⁹/L. However, RE-LYMP% and RE-LYMP# demonstrated significant sex-related differences requiring sex-specific RIs. Female RE-LYMP% ranged from 0.20% to 1.10% and male values from 0.10% to 0.90%, while RE-LYMP# ranged from 0.01 to 0.08 × 10⁹/L in females and 0.01 to 0.06 × 10⁹/L in males.

Reference intervals for NEUT-GI, NEUT-RI, RE-LYMP, and AS-LYMP were established in healthy Thai adults. Most EIPs did not require demographic partitioning, whereas RE-LYMP% and RE-LYMP# required sex-specific intervals.