Granulocyte colony-stimulating factor in bronchoalveolar lavage fluid is a potential biomarker for prognostic prediction of idiopathic pulmonary fibrosis.

BACKGROUND/AIMS: Neutrophilia is frequently observed in bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. Granulocyte colony-stimulating factor (G-CSF) is a potent neutrophil-activating glycoprotein. However, the clinical implications of G-CSF remain poorly understood.in patients with IPF. Therefore, we evaluated the relationship between the G-CSF concentration in BALF and the progression of fibrosis, including in terms of the decline in lung function and long-term survival rate. METHODS: G-CSF concentrations were measured in BALF using enzyme-linked immunosorbent assay (ELISA). The survival rate was estimated using Kaplan-Meier survival analyses. RESULTS: G-CSF protein levels were significantly higher in IPF (n = 87; 1.88 [0 to 5.68 pg/mL]), nonspecific interstitial pneumonia (n = 22; 0.58 [0 to 11.64 pg/mL]), and hypersensitivity pneumonitis (n = 19; 2.48 [0.46 to 5.71 pg/mL]) patients than in normal controls (n = 33; 0 [0 to 0.68 pg/mL]) (all p < 0.01). A receiver operating characteristic curve showed a difference in G-CSF levels between IPF and NC (area under the curve, 0.769): The G-CSF cut-off of 0.96 pg/mL indicated 84.9% specificity and 63.2% sensitivity for IPF. The survival rate was significantly lower in the group with G-CSF > 2.872 pg/mL than in the group with ≤ 2.872 pg/mL (hazard ratio, 2.69; p = 0.041). The annual decline in diffusing capacity of the lung for carbon monoxide was positively correlated with the G-CSF level (p = 0.018). CONCLUSION: G-CSF may participate in the development of IPF and be useful for predicting the prognosis of IPF. Therefore, G-CSF should be analyzed in BALF, in addition to differential cell counts.

Association of GSTM1 and GSTT1 Null Genotypes with Toluene Diisocyanate-Induced Asthma.

BACKGROUND: Toluene diisocyanate (TDI) causes occupational asthma by generating oxidative stress, leading to tissue injury and inflammation. Glutathione transferases (GSTs) are detoxifying enzymes that eliminate oxidative stress. We examined whether the genotypes of the GSTM1 and GSTT1 genes are associated with TDI-induced occupational asthma (TDI-OA). METHODS: The study population consisted of 26 asthmatics with a positive response to the TDI challenge (TDI-PA) and 27 asthmatics with negative responses (TDI-NA). GSTM1 and GSTT1 null and wild-type genotypes were determined using multiplex PCR. The plasma GSTM1 and GSTT1 protein concentrations were determined using ELISA. RESULTS: The GSTM1 null genotype was more frequent in the TDI-PA than in the TDI-NA (77.8 vs. 50.0%, OR = 3.5, p=0.03), while the frequency of the GSTT1 null genotype tended to be higher in the TDI-PA than in the TDI-NA (59.3 vs. 42.3%, OR = 1.98, p=0.21). When analyzed together, the GSTM1/GSTT1 null genotype was more frequent in the TDI-PA than in the TDI-NA (48.2 vs. 15.3%, OR = 6.5, p=0.04). The decline in the FEV in 1 s after TDI challenge was higher with the GSTM1/GSTT1 null than the GSTM1 wild-type/GSTT1 null genotypes (24.29% vs. 7.47%, p=0.02). The plasma GSTM1 level was lower with the GSTM1 null than with the GSTM1 wild-type genotypes both before (13.7 vs. 16.6 ng/mg, p=0.04) and after (12.9 vs. 17.1 ng/mg, p=0.007) the TDI challenge, while the GSTT1 level was not changed with either the GSTT1 null or wild-type genotype. CONCLUSIONS: The GSTM1 null genotype, but not GSTT1 alone, may confer susceptibility to TDI-OA. However, the genetic effect of the GSTM1 null genotype may be enhanced synergistically by the GSTT1 null genotype. The genetic effect of GSTM1 was validated in the plasma as the GSTM1 protein level. Therefore, the GSTM1 and GSTT1 genotypes may be useful diagnostic markers for TDI-OA.