Abstract
BackgroundBiomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters.MethodsThis retrospective study included 549 Korean patients with rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and other CTDs with or without concurrent ILD. Serum KL-6 concentration (U/mL) was measured using the latex-enhanced immunoturbidimetric assay method. CT and PFT results were collected within 1 year of serum collection. A semiquantitative grade of ILD extent was evaluated through CT scan (grade 1, 0–25%; grade 2, 26–50%; grade 3, 51–75%; grade 4, 76–100%).ResultsCTD-ILD patients (n = 165) had elevated serum KL-6 levels compared to CTD patients without ILD (n = 384) (p < 0.001), and those findings were preserved after adjusting for age, sex, and CTD type. The semiquantitative grade of ILD on CT scan was significantly proportional to the KL-6 level, and the optimal cut-off KL-6 value effectively differentiated each ILD grade. The percent diffusing capacity of the lung for carbon monoxide (DLCO) (p < 0.001) and forced vital capacity (FVC) (p < 0.001) parameters had a moderate, negative correlation with the KL-6 level.ConclusionSerum KL-6 levels were increased in CTD-ILD patients and had a positive correlation with CT grade and a negative correlation with FVC and DLCO. Serum KL-6 levels may reflect CTD-ILD severity.
Highlights
Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-Interstitial lung disease (ILD))
Clinical characteristics of the study population Patients with connective tissue diseases (CTDs)-ILD (n = 165) had elevated serum Krebs von den Lungen 6 (KL-6) levels compared to CTD patients without ILD (n = 384) (p < 0.001) (Table 1)
The results showed that the serum KL-6 level was consistently higher in the ILD group (p < 0.001)
Summary
Biomarkers have been actively investigated to supplement functional and imaging modalities to predict the severity, therapeutic responsiveness, and progression of connective tissue disease-associated interstitial lung disease (CTD-ILD). This study aimed to evaluate Krebs von den Lungen 6 (KL-6) as a potential biomarker reflecting the severity of CTD-ILD as assessed through computed tomography (CT) and pulmonary function test (PFT) parameters. Interstitial lung disease (ILD) is commonly associated with various connective tissue diseases (CTDs), such as rheumatoid arthritis (RA), systemic sclerosis (SSc), inflammatory myositis (IM), Sjogren’s syndrome (SS), and systemic lupus erythematosus (SLE) [1]. High-resolution computed tomography (HRCT) and pulmonary function test (PFT) are the two major modalities used to diagnose and evaluate CTDILD rather than lung biopsy [12]. The corresponding type of CTD-ILD suggested by HRCT is insufficient to evaluate the current disease status or predict disease progression [15]. HRCT is considered a standard for evaluating CTD-ILD
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