Circulatory Serum Krebs von Den Lungen-6 and Surfactant Protein-D Concentrations Predict Interstitial Lung Disease Progression and Mortality.
Circulatory Serum Krebs von Den Lungen-6 and Surfactant Protein-D Concentrations Predict Interstitial Lung Disease Progression and Mortality.
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需要生物标志物来预测间质性肺疾病（ILD）的预后，包括死亡率。Krebs von den Lungen-6 （KL-6）和表面活性剂蛋白D （SP-D）与所有ild的肺损伤和纤维化相关，并与重要的临床结果相关。虽然这两种生物标志物与ILD的预后相关，但还没有研究评估它们联合使用的预测潜力。本研究旨在确定KL-6和SP-D是否与疾病预后不良和死亡率有关。此外，我们计划研究KL-6和SP-D浓度的变化是否与肺功能的变化相对应，以及系列测量是否提高了它们识别疾病进展和死亡率的预测潜力。44名ILD患者参与了一项为期6个月的前瞻性纵向观察研究。死亡的ILD患者KL-6水平最高（3990.4 U/mL (3490.0-4467.6)）， SP-D水平最高（256.1 ng/mL(217.9-260.0)），其次是恶化的患者：KL-6水平为1357.0 U/mL (822.6-1543.4)， SP-D水平为191.2 ng/mL（152.8-210.5）。广义线性模型（GLM）分析显示，用力肺活量（FVC）、肺一氧化碳弥散量（DLCO）、1s用力呼气量（FEV1）和动脉氧分压（PaO2）的变化与KL6 （p = 0.016、0.014、0.027、0.047）和SP-D （p = 0.008、0.012、0.046、0.020）的变化相关。通过Cox回归分析，KL-6（优势比（OR）： 2.87(1.06-7.79)）和SPD （OR: 1.76(1.05-2.97)）是疾病进展的独立预测因子，KL-6（风险比（HR）： 3.70(1.46-9.41)）和SPD （HR: 2.58(1.01-6.59)）是死亡的独立预测因子。综合生物标志物（KL6 + SPD + CT + FVC）预测疾病进展（AUC: 0.797）和死亡（AUC: 0.961）的能力最强。升高的KL-6和SPD水平是预测ILD严重程度、进展和结局的重要生物标志物。高基线水平或6个月随访期间水平升高表明预后不良。将KL6和SPD与常规测量相结合可以产生更有效的预后指标。需要临床研究来测试额外的干预措施，未来的研究将确定这种联合生物标志物是否有益于全球不同的种族。
There is a need for biomarkers to predict outcomes, including mortality, in interstitial lung disease (ILD). Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are associated with lung damage and fibrosis in all ILDs and are related to important clinical outcomes. Though these two biomarkers have been associated with ILD outcomes, there are no studies that have evaluated their predictive potential in combination. This study aims to determine whether KL-6 and SP-D are linked to poor disease outcomes and mortality. Additionally, we plan to examine whether changes in KL-6 and SP-D concentrations correspond with changes in lung function and whether serial measurements improve their predictive potential to identify disease progression and mortality. Forty-four patients with ILD participated in a prospective 6-month longitudinal observational study. ILD patients who succumbed had the highest KL-6 levels (3990.4 U/mL (3490.0–4467.6)) and highest SP-D levels (256.1 ng/mL (217.9–260.0)), followed by those who deteriorated: KL-6 levels 1357.0 U/mL (822.6–1543.4) and SP-D levels 191.2 ng/mL (152.8–210.5). The generalized linear model (GLM) analysis demonstrated that changes in forced vital capacity (FVC), diffusing capacity of lungs for carbon monoxide (DLCO), forced expiratory volume in 1 s (FEV1), and partial pressure of arterial oxygen (PaO2) were correlated to changes in KL6 (p = 0.016, 0.014, 0.027, 0.047) and SP-D (p = 0.008, 0.012, 0.046, 0.020), respectively. KL-6 (odds ratio (OR): 2.87 (1.06–7.79)) and SPD (OR: 1.76 (1.05–2.97)) were independent predictors of disease progression, and KL-6 (hazard ratio (HR): 3.70 (1.46–9.41)) and SPD (HR: 2.58 (1.01–6.59)) were independent predictors of death by Cox regression analysis. Combined biomarkers (KL6 + SPD + CT + FVC) had the strongest ability to predict disease progression (AUC: 0.797) and death (AUC: 0.961), on ROC analysis. Elevated KL-6 and SPD levels are vital biomarkers for predicting the severity, progression, and outcomes of ILD. High baseline levels or an increase in levels over a six-month follow-up despite treatment indicate a poor prognosis. Combining KL6 and SPD with conventional measures yields a more potent prognostic indicator. Clinical studies are needed to test additional interventions, and future research will determine if this combined biomarker benefits different ethnicities globally.
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