Circulatory Serum Krebs von Den Lungen-6 and Surfactant Protein-D Concentrations Predict Interstitial Lung Disease Progression and Mortality

Abstract

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.

Study of the Activity of Indicators of Systemic Inflammation and Surfactant Protein D in Chronic Obstructive Pulmonary Disease, their Relationship with the Nutritional Status of Patients

“…В последнее время одним из потенциальных легочно-специфических показателей считается сурфактантный белок D. Предыдущие исследования продемонстрировали нарушение регуляции некоторых отдельных компонентов сурфактанта при ХОБЛ . Достоверное повышение его уровня в плазме крови больных ХОБЛ независимо от статуса курения свидетельствует, что СБД может рассматриваться как специфический маркер поражения респираторной системы при этом заболевании Rai et al, 2023].…”

“…Хотя снижение объема форсированного выдоха (ОФВ1) считается важным прогностическим маркером при ХОБЛ, исследования показали, что воспалительные маркеры могут предоставлять ценную информацию для диагностики и мониторинга ХОБЛ [Ташметова, 2022;Rai et al, 2023]. Уже давно сообщалось, что снижение функции легких связано с наличием нескольких факторов, включая увеличение частоты обострений ХОБЛ.…”

Peripheral Blood Biomarker Krebs von den Lungen 6 (KL-6) for Interstitial and Other Lung Diseases

“…Концентрация Krebs von den Lungen 6 и сурфактантного белка D (SP-D) в сыворотке крови может предсказывать прогрессирование интерстициального заболевания легких и смертельный исход [16].…”