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支气管肺泡灌洗液中的粒细胞集落刺激因子是特发性肺纤维化预后预测的潜在生物标志物。

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

机构信息

Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang University, Bucheon, Korea.

Division of Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.

出版信息

Korean J Intern Med. 2022 Sep;37(5):979-988. doi: 10.3904/kjim.2021.442. Epub 2022 Jun 22.

Abstract

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.

摘要

背景/目的:特发性肺纤维化(IPF)患者的支气管肺泡灌洗液(BALF)中常观察到嗜中性粒细胞增多。粒细胞集落刺激因子(G-CSF)是一种有效的嗜中性粒细胞激活糖蛋白。然而,G-CSF 在 IPF 患者中的临床意义仍知之甚少。因此,我们评估了 BALF 中 G-CSF 浓度与纤维化进展之间的关系,包括肺功能下降和长期生存率。

方法

使用酶联免疫吸附测定(ELISA)测量 BALF 中的 G-CSF 浓度。使用 Kaplan-Meier 生存分析估计生存率。

结果

与正常对照组(n = 33;0 [0 至 0.68 pg/mL])相比,IPF(n = 87;1.88 [0 至 5.68 pg/mL])、非特异性间质性肺炎(n = 22;0.58 [0 至 11.64 pg/mL])和过敏性肺炎(n = 19;2.48 [0.46 至 5.71 pg/mL])患者的 G-CSF 蛋白水平显著升高(均 p < 0.01)。ROC 曲线显示 IPF 和 NC 之间 G-CSF 水平的差异(曲线下面积,0.769):G-CSF 截断值为 0.96 pg/mL 时,对 IPF 的特异性为 84.9%,敏感性为 63.2%。G-CSF > 2.872 pg/mL 组的生存率明显低于 G-CSF ≤ 2.872 pg/mL 组(风险比,2.69;p = 0.041)。一氧化碳弥散量的年下降与 G-CSF 水平呈正相关(p = 0.018)。

结论

G-CSF 可能参与 IPF 的发生,并有助于预测 IPF 的预后。因此,除了差异细胞计数外,还应分析 BALF 中的 G-CSF。

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