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进行性纤维化间质性肺疾病的诊断和预后生物标志物。

Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease.

机构信息

Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

Department of Allergy, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

出版信息

PLoS One. 2023 Mar 17;18(3):e0283288. doi: 10.1371/journal.pone.0283288. eCollection 2023.

Abstract

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

摘要

尚无生物标志物可用于预测进行性纤维化间质性肺病(PF-ILD)的纤维化进展或预后。我们研究了支气管肺泡灌洗液(BALF)中的生物标志物用于 PF-ILD 的诊断和预后评估。本回顾性研究共纳入了 120 名可诊断为 PF-ILD 或非 PF-ILD 的间质性肺炎患者。根据 Cottin 的定义诊断 PF-ILD。所有患者均接受支气管镜检查和 BALF 采集。我们评估了血液和 BALF 参数、高分辨率计算机断层扫描(HRCT)模式和肺功能数据,以确定影响 PF-ILD 诊断和预后的因素。单因素逻辑分析显示,年龄、性别、BALF 白细胞分数(中性粒细胞、淋巴细胞、嗜酸性粒细胞和中性粒细胞与淋巴细胞比值)、BALF 流式细胞术分析(CD8)和 HRCT 上特发性肺纤维化/普通间质性肺炎模式与 PF-ILD 诊断相关。多因素逻辑回归分析显示,性别(男性)、年龄(截点 62 岁,曲线下面积 [AUC] 0.67;敏感性 0.80;特异性 0.47)、BALF 白细胞分数(NLR、中性粒细胞和淋巴细胞)和 BALF 中的 CD8(截点 34.2;AUC 0.66;敏感性,0.74;特异性,0.62)是 PF-ILD 的独立诊断预测因素。在 BALF 中,NLR(截点 8.70,AUC 0.62;敏感性 0.62;特异性 0.70)、中性粒细胞计数(截点 3.0,AUC 0.59;敏感性 0.57;特异性 0.63)和淋巴细胞计数(截点 42.0,AUC 0.63;敏感性 0.77;特异性 0.53)是独立的诊断预测因子。在 PF-ILD 患者(n=77)中,乳酸脱氢酶(截点 275,AUC 0.69;敏感性 0.57;特异性 0.78)、Krebs von den Lungen-6(截点 1,140,AUC 0.74;敏感性 0.71;特异性 0.76)、基线用力肺活量(FVC)(截点 1.75 L,AUC 0.71;敏感性,0.93;特异性,0.46)和 BALF 中性粒细胞比(截点 6.0,AUC 0.72;敏感性 0.79;特异性 0.80)与 3 年内死亡相关。BALF 细胞比值,特别是中性粒细胞比值,与 PF-ILD 的诊断和预后相关。这些发现可能有助于间质性肺炎患者的管理。

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