Serum cytokines markers in toluene diisocyanate-induced asthma

Toluene diisocyante-induced occupational asthma (TDI-OA) is an inflammatory disease of airway, composing inflammatory cells and cytokines associated with airway remodeling. Majority of the patients with TDI-OA presented persistent asthma. Therefore, early diagnosis is essential for the favorable prognosis. We investigated to identify serologic markers for early diagnosis of TDI-OA.

We enrolled 69 patients with TDI-OA and 95 asymptomatic exposed controls (AECs). Neutrophil-related cytokines, including myeloperoxidase (MPO) and interleukin-8 (IL-8), as well as airway remodeling-related cytokines, including transforming growth factor-β1 (TGF-β1), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and vascular endothelial growth factor (VEGF), were measured by ELISA in the sera of each subject. To evaluate the validity of the each cytokine and combined cytokines for discriminating between TDI-OA and AEC, Receiver operating characteristic (ROC) curve was used.

There were significant differences in the serum levels of MMP-9 and VEGF between two groups (p < 0.05). Using the optimal cutoff value of MMP-9 (182.96 ng/mL), the sensitivity and specificity were 79.7% and 80.0%, respectively, with the area under the curve (AUC) of 0.815. When the cytokines were combined to improve sensitivity, the combined values of MMP-9, VEGF, and IL-8 comprised the best set, for which the AUC increased to 0.822 and the sensitivity increased to 82.6% but specificity decreased to 75.8%.

The single serum cytokine MMP-9 level or the combined cytokines MMP-9, VEGF, and IL-8 can be used as meaningful serologic markers for identifying patients with TDI-OA among exposed workers.