Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth Factor-β, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine Deaminase in Pleural Effusion

Lung. 2018 Apr;196(2):249-254. doi: 10.1007/s00408-018-0090-1. Epub 2018 Jan 20.

Abstract

Purpose: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid.

Methods: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted.

Results: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-β was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001).

Conclusions: VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Keywords: Interleukin-8; Pleural LDH/ADA ratio; Transforming growth factor-β; Vascular endothelial growth factor; Vascular permeability.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Deaminase / analysis*
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Diagnosis, Differential
  • Empyema, Pleural / complications
  • Empyema, Pleural / diagnosis
  • Female
  • Heart Failure / complications
  • Heart Failure / diagnosis
  • Humans
  • Interleukin-8 / analysis*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / diagnosis
  • L-Lactate Dehydrogenase / analysis*
  • Male
  • Middle Aged
  • Pleural Effusion / diagnosis*
  • Pleural Effusion / enzymology
  • Pleural Effusion / etiology
  • Pleural Effusion, Malignant / diagnosis
  • Pleural Effusion, Malignant / enzymology
  • Pleural Effusion, Malignant / etiology
  • Pneumonia / complications
  • Pneumonia / diagnosis
  • Predictive Value of Tests
  • Prospective Studies
  • Transforming Growth Factor beta / analysis
  • Tuberculosis / complications
  • Tuberculosis / diagnosis
  • Vascular Endothelial Growth Factor A / analysis*

Substances

  • Biomarkers
  • CXCL8 protein, human
  • Interleukin-8
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • L-Lactate Dehydrogenase
  • Adenosine Deaminase