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中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (06) : 904 -910. doi: 10.3877/cma.j.issn.1674-6902.2025.06.009

论著

支气管肺泡灌洗液PTPN2水平与矽肺患者疾病严重程度和肺功能的关系研究
王春, 许斌, 刘丹, 陶承志, 林欢, 张海涛†()   
  1. 210029　南京，东南大学医学院附属南京胸科医院呼吸内科
  • 收稿日期:2025-07-28 出版日期:2025-12-25
  • 通信作者: 张海涛
  • 基金资助:
    江苏省科技计划项目(SBE2018740476)

Study on the relationship between bronchoalveolar lavage fluid PTPN2 level and disease severity and pulmonary function in patients with silicosis

Chun Wang, Bin Xu, Dan Liu, Chengzhi Tao, Huan Lin, Haitao Zhang†()   

  1. Department of Respiratory Medicine, Nanjing Chest Hospital Affiliated to the School of Medicine, Southeast University, Nanjing 210029, China
  • Received:2025-07-28 Published:2025-12-25
  • Corresponding author: Haitao Zhang
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引用本文：

王春, 许斌, 刘丹, 陶承志, 林欢, 张海涛. 支气管肺泡灌洗液PTPN2水平与矽肺患者疾病严重程度和肺功能的关系研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(06): 904-910.

Chun Wang, Bin Xu, Dan Liu, Chengzhi Tao, Huan Lin, Haitao Zhang. Study on the relationship between bronchoalveolar lavage fluid PTPN2 level and disease severity and pulmonary function in patients with silicosis[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 904-910.

目的

分析支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)非受体型蛋白酪氨酸磷酸酶2(protein tyrosine phosphatase non-receptor type 2, PTPN2)水平与矽肺患者疾病严重程度和肺功能的关系。

方法

选择2021年5月至2025年2月在南京市胸科医院首次接受支气管肺泡灌洗的矽肺患者56例为观察组，其中Ⅰ期31例，Ⅱ期16例，Ⅲ期9例。纳入同期因胸痛或咳嗽而接受支气管肺泡灌洗(X射线胸片不能确定尘肺样变化)未达到I期矽肺的受试煤矿工人51例为对照组。通过酶联免疫吸附试验法检测受试者BALF PTPN2水平。对矽肺患者BALF PTPN2水平与肺功能进行相关性分析。

结果

观察组FEV1%[68.50(54.20，79.75)]、FVC%[79.00(62.00，91.50)]、FEV1/FVC[65.50(56.50，69.75)]、DLCO%[76.00(54.25，88.00)]水平低于对照组[82.00(73.95，82.05)]，[88.00(82.00，92.25)]，[72.80(72.00，73.85)]，[84.00(82.00，89.00)](P<0.05)；BALF样本中，观察组IL-6[10.95(6.10，20.83)]pg/ml、IL-8[11.54(5.02，21.58)]pg/ml、TNF-α[10.13(7.63，17.68)]pg/ml、MCP-1[294.53(237.48，403.27)]pg/ml、IP-10[170.43(144.69，194.47)]pg/ml水平以及FENO高于对照组IL-6[6.27(5.64，6.96)]pg/ml、IL-8[8.07(4.26，16.71)]pg/ml、TNF-α[8.79(5.76，19.87)]pg/ml、MCP-1[254.95(154.70，366.58)]pg/ml、IP-10[127.48(91.00，145.87)]pg/ml(P<0.05)。观察组诊断时PTPN2水平[446.14(337.18，717.30)]pg/ml高于对照组[143.46(85.65，189.17)]pg/ml(P<0.05)。BALF PTPN2诊断矽肺的ROC曲线下面积(AUC)为0.869(95%CI：0.802~0.936)。PTPN2水平在不同疾病严重程度组之间存在统计学差异，Ⅲ期患者的PTPN2水平最高[1 879.10(1133.18，2 145.99)pg/ml]，Ⅱ期患者的PTPN2水平次之[722.53(383.90，1 009.59)pg/ml]，Ⅰ期患者的PTPN2水平最低[348.50(197.72，453.50)pg/ml](H＝23.247，P<0.001)。BALF PTPN2区分Ⅱ~Ⅲ期和Ⅰ期矽肺患者的AUC可达到0.897(95%CI：0.812~0.971)。通过Logistic回归发现BALF PTPN2高水平是Ⅱ~Ⅲ期矽肺进展的独立预测因子(P<0.05)。矽肺患者BALF PTPN2水平与FEV1%(r＝－0.359，P＝0.007)、FVC%(r＝－0.409，P＝0.002)、FEV1/FVC(r＝－0.309，P＝0.021)和DLCO%(r＝－0.285，P＝0.033)呈显著负相关。矽肺患者BALF PTPN2水平与炎症和纤维化指标IL-6、IL-8、TNF-α、MCP-1、IP-10呈显著正相关(P<0.05)。

结论

BALF PTPN2水平升高与矽肺加重和肺功能恶化显著相关。PTPN2可能参与矽肺病的病理生理过程，并有望成为矽肺诊断和疾病恶化风险评估的潜在生物标志物。

关键词: 矽肺, 支气管肺泡灌洗液, 非受体型蛋白酪氨酸磷酸酶2, 严重程度, 肺功能
Objective

To explore the relationship between the level of protein tyrosine phosphatase non-receptor type 2 (PTPN2) in bronchoalveolar lavage fluid (BALF) and the severity of the disease and lung function in patients with silicosis.

Methods

By a simple sampling method, a total of 56 patients with silicosis who underwent bronchoalveolar lavage for the first time in Nanjing Chest Hospital from May 2021 to February 2025 were prospectively selected as the research subjects, including 31 cases in stage Ⅰ, 16 cases in stage Ⅱ, and 9 cases in stage Ⅲ. In addition, 51 coal miners who underwent bronchoalveolar lavage due to chest pain or cough during the same period (X-ray chest films could not determine pneumoconiosis changes) and did not reach stage Ⅰ silicosis were included as the control group. The level of PTPN2 in BALF of the subjects was detected by enzyme-linked immunosorbent assay. A correlation analysis was conducted between the levels of PTPN2 in BALF and lung function in silicosis patients.

Results

The level of BALF PTPN2 at diagnosis in the silicosis group was significantly higher than that in the control group (P<0.05). The area under the ROC curve (AUC) of BALF PTPN2 for diagnosing silicosis was 0.869 (95%CI: 0.802-0.936). There were significant differences in PTPN2 levels among different disease severity groups. The PTPN2 level was the highest in stage Ⅲ patients, followed by that in stage Ⅱ patients, and the lowest in stage Ⅰ patients (P<0.05). The AUC of BALF PTPN2 in differentiating patients with stage Ⅱ~Ⅲ and stage Ⅰ silicosis could reach 0.897(95%CI: 0.812~0.971). Logistic regression analysis showed that the higher level of BALF PTPN2 was an independent predictor of the progression of stage Ⅱ-Ⅲ silicosis (P<0.05). Spearman′s rank correlation analysis showed that the BALF PTPN2 level in patients with silicosis was significantly negatively correlated with forced expiratory volume in 1 second percentage (FEV1%) predicted value (r=-0.359, P=0.007), forced vital capacity percentage (FVC%) predicted value (r=-0.409, P=0.002), FEV1/FVC (r=-0.309, P=0.021) and diffusion lung carbon monoxide (r=-0.285, P=0.033). Besides, The level of BALF PTPN2 in patients with silicosis was significantly positively correlated with inflammatory and fibrotic indicators such as interleukin (IL)-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein 1, and interferon-induced protein 10(P<0.05).

Conclusion

The elevated level of BALF PTPN2 is significantly associated with the aggravation of silicosis and the deterioration of lung function. PTPN2 may be involved in the pathophysiological process of silicosis and is expected to become a potential biomarker for the diagnosis of silicosis and the assessment of the risk of disease deterioration.

Key words: Silicosis, Bronchoalveolar lavage fluid, Protein tyrosine phosphatase non-receptor type 2, Severity, Lung function
表1 两组患者临床资料结果比较[M(Q25，Q75)]
临床资料 观察组(n＝56) 对照组(n＝51) t/χ2/Z值 P值
BALF样本测定        
WBC(×109/L) 11.00(8.70，13.10) 10.10(8.90，12.70) －0.415 0.678
NEU%(%) 70.00(60.00，83.00) 57.00(47.00，74.00) －3.108 0.002
LYM%(%) 36.00(23.00，47.00) 37.00(25.00，47.00) －0.456 0.649
MONO%(%) 7.00(5.00，10.00) 7.00(5.00，10.00) －0.003 0.997
EOS%(%) 3.00(1.00，4.00) 3.00(1.00，4.00) －0.957 0.338
IL-6(pg/ml) 10.95(6.10，20.83) 6.27(5.64，6.96) －4.076 0.000
IL-8(pg/ml) 11.54(5.02，21.58) 8.07(4.26，16.71) －1.999 0.046
TNF-α(pg/ml) 10.13(7.63，17.68) 8.79(5.76，19.87) －2.609 0.009
MCP-1(pg/ml) 294.53(237.48，403.27) 254.95(154.70，366.58) －2.305 0.021
IP-10(pg/ml) 170.43(144.69，194.47) 127.48(91.00，145.87) －4.460 0.000
FENO(ppb) 28.50(24.50，33.50) 15.50(12.50，24.00) －4.729 0.000
FEV1%(%) 68.50(54.20，79.75) 82.00(73.95，82.05) －4.176 0.000
FVC%(%) 79.00(62.00，91.50) 88.00(82.00，92.25) －2.289 0.022
FEV1/FVC 65.50(56.50，69.75) 72.80(72.00，73.85) －4.259 0.000
DLCO% 76.00(54.25，88.00) 84.00(82.00，89.00) －3.102 0.002
图1 PTPN2水平与矽肺疾病严重程度的关系
表2 二元Logistic回归分析影响Ⅱ-Ⅲ期矽肺进展的临床因素
临床指标 单因素分析 多因素分析
OR 95%CI P值 OR 95%CI P值
年龄(≥45岁vs. <45岁) 1.046 0.938~1.167 0.415 － － －
性别(女性vs.男性) 0.810 0.278~2.355 0.698 － － －
体质量指数(≥24 kg/m2 vs. <24 kg/m2) 0.979 0.828~1.159 0.809 － － －
饮酒史(有vs.无) 0.892 0.310~2.566 0.832 － － －
糖尿病(有vs.无) 1.286 0.287~5.754 0.742 － － －
高脂血症(有vs.无) 2.447 0.685~8.746 0.168 － － －
高血压(有vs.无) 2.526 0.748~8.537 0.136 － － －
连续变量     － － －  
粉尘暴露年限 1.143 1.008~1.296 0.037 1.042 0.828~1.312 0.724
BALF WBC 1.056 0.896~1.245 0.514 － － －
BALF NEU% 1.031 0.994~1.070 0.098 － － －
BALF LYM% 0.982 0.945~1.021 0.363 － － －
BALF MONO% 1.055 0.929~1.197 0.410 － － －
BALF EOS% 0.949 0.802~1.124 0.545 － － －
BALF IL-6 1.073 1.013~1.135 0.016 1.041 0.943~1.150 0.427
BALF IL-8 1.050 1.007~1.095 0.023 1.056 0.984~1.150 0.131
BALF TNF-α 1.057 0.999~1.118 0.053 － － －
BALF MCP-1 1.009 1.003~1.015 0.002 1.006 0.996~1.017 0.224
BALF IP-10 1.006 0.999~1.012 0.095 － － －
BALF PTPN2 1.007 1.003~1.011 0.000 1.008 1.002~1.013 0.009
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你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？