Prognostic role of blood KL-6 in rheumatoid arthritis-associated interstitial lung disease.

Ho Cheol Kim,Jin Woo Song,Joseph Jacob,Kwang Hun Choi,Masataka Kuwana

doi:10.1371/journal.pone.0229997

Abstract

Rheumatoid arthritis–associated interstitial lung disease (RA-ILD) has a variable clinical course for which predicting prognosis is difficult. However, the role of blood biomarkers in RA-ILD is ill-defined. The aim of this study was to investigate the prognostic value of Krebs von den Lungen-6 (KL-6) levels in RA-ILD patients. The medical records of 84 patients with RA-ILD were retrospectively reviewed. Plasma KL-6 levels were measured by Nanopia KL-6 assay (SEKISUI MEDICAL, Tokyo), using latex-enhanced immunoturbidimetric assay. The median follow-up period was 61 months. Mean age was 61.4 years, 45.2% were men, 44.0% were ever-smokers, and 35.7% showed a usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography. The median KL-6 level at baseline was 741.2 U/mL (interquartile range, 439.7–1308.9 U/mL). On multivariate logistic regression analysis, a high KL-6 level (≥ 640 U/mL) was an independently associated with a UIP pattern (odds ratio [OR], 5.173; P = 0.005) with old age (OR, 1.104, P = 0.005). On multivariate Cox analysis, a high KL-6 level (≥ 685 U/mL) was an independent prognostic factor for the mortality (hazard ratio [HR], 2.984; P = 0.016) with a older age (HR, 1.061; P = 0.030), male sex (HR, 3.610; P = 0.001), lower forced vital capacity (HR, 0.957; P = 0.002), and a UIP pattern (HR, 4.034; P = 0.002). Our results suggest that high KL-6 levels might be useful as a biomarker for the presence of a UIP pattern and prognosis in patients with RA-ILD.

Highlights

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) that is associated with morbidity and mortality [1,2]
Previous studies reported that old age, male sex, reduced lung function, a usual interstitial pneumonia (UIP) pattern, and extensive disease on high-resolution computed tomography (HRCT) are associated with poor prognosis in RA-associated interstitial lung disease (RA-ILD) [5,6,7,8,9]
A surgical lung biopsy was performed in 24 patients and revealed that UIP was the most common histopathologic pattern (62.5%), followed by nonspecific interstitial pneumonia (NSIP) (20.8%) and organizing pneumonia (16.7%)

Summary

Introduction

Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) that is associated with morbidity and mortality [1,2]. Previous studies reported that old age, male sex, reduced lung function (forced vital capacity [FVC], diffusing capacity of the lung for carbon monoxide [DLco]), a usual interstitial pneumonia (UIP) pattern, and extensive disease on high-resolution computed tomography (HRCT) are associated with poor prognosis in RA-ILD [5,6,7,8,9]. Their predictive capacity may be limited by insufficient respiratory effort, complications such as emphysema or pulmonary hypertension, or interobserver variability [10,11].

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