Concentrations of HMGB1 and Hsp70 of healthy subjects in upper and lower airway: Literature Review and Meta-analysis

Abstract

Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control concentrations in the airways have not yet been determined. This study aimed to evaluate concentration of healthy subjects for both these proteins in the upper and lower airways via meta-analysis. We searched MEDLINE, EMBASE, and Google Scholar for articles describing concentration of healthy subjects for these proteins. Data from healthy populations were combined using a random-effects model, and subgroup and sensitivity analyses were performed to determine between-study heterogeneity. We analyzed 22 studies involving 485 patients. Concentration of healthy subjects of high-mobility group box 1 and heat-shock protein 70 varied from "not detected" to 326.13 ng/mL and from 0.20 pg/mL to 9240.00 pg/mL, respectively, with the values showing significant heterogeneity. Subgroup analysis for high-mobility group box 1 revealed 13.63 ng/mL (95% CI 12.13-15.14), 100.31 ng/mL (95% CI -31.28-231.91), 9.54 ng/mL (95% CI 8.91-10.17), and 65.82 ng/mL (95% CI 55.51-76.14) for the lower airway, upper airway, pediatric populations, and adults, respectively, whereas that for heat-shock protein 70 revealed 20.58 pg/mL (95% CI 7.87-33.29) for the lower airway and 9240.00 ±11820 pg/mL for the upper airway. Although concentrations of healthy subjects of these proteins varied in the upper and lower airways, the levels of both these proteins were higher in the upper airway than in the lower airway, and these concentrations differed according to the age and sampling procedure. Our findings support the further evaluation of these proteins as biomarkers for airway-related diseases.

Keywords: biomarkers; heat-shock protein 70; high-mobility group box 1 protein; meta-analysis; reference ranges.

Figure 1

Flow diagram of the search process and the inclusion and exclusion criteria for the meta-analysis.

Figure 2

Forest plots of the concentration of healthy subjects of HMGB1 in the upper and lower airways. (A) Plot for HMGB1 in the upper and lower airways. (B) Plot for sensitivity analysis, excluding one study at a time, for HMGB1 in the upper and lower airways. (C, D) Plots for HMGB1 in the (C) lower and (D) upper airways. The figure depicts individual trials as filled squares with sizes relative to the sample size and the 95% confidence interval of the difference as the solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.

Figure 3

Forest plots of the concentration of healthy subjects of Hsp70 in the upper and lower airways. The figure depicts individual trials as filled squares with sizes relative to the sample size and the 95% confidence interval of the difference as the solid line. The diamond shape indicates the pooled estimate and uncertainty for the combined effect.