Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Department of Allergy, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
PLoS One. 2023 Mar 17;18(3):e0283288. doi: 10.1371/journal.pone.0283288. eCollection 2023.
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.
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。