Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis-associated interstitial lung disease.

INTRODUCTION

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (RA-ILD) is a serious systemic RA manifestation with high mortality that needs proper, accurate, and sensitive assessment tools.

OBJECTIVES

Firstly, evaluate serum Krebs von den Lungen-6 (KL-6) levels and lung ultrasound B lines (LUS B lines) score in RA-ILD correlating them with the severity of ILD assessed by high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). Secondly, determine cut-off values for LUS and KL-6 in RA-ILD assessment and outcome prediction.

METHODS

A case-control study included seventy-five RA-ILD patients with an equal number of matched RA patients without ILD. Clinical assessment includes DAS-28 and PFTs, laboratory assessment of serum KL-6 by latex-enhanced immunoturbidimetric assay, and radiological evaluation of ILD using semiquantitative CT grade and LUS B lines.

RESULTS

RA-ILD patients had significantly higher serum KL6 compared to those without ILD (1025.5 ± 419.6 vs. 237.5 ± 51.9, p ≤ 0.001). Serum KL6 was positively correlated with HRCT and LUS scores (r = 0.93, r = 0.97, respectively) with negative correlation with FVC% and FEV1% (r = - 0.93, r = - 0.91, respectively). LUS was positively correlated with KL6 and HRCT (r = 0.97, r = 0.944, respectively) while, negatively correlated with PFTs. Cut-off values of KL6 and LUS were 277.5 U/ml and < 5.5, with AUC 0.878 and 1, sensitivity 86.7% and 100%, and specificity 88% and 100%, respectively.

CONCLUSIONS

The non-invasive, radiation-free LUS with a score < 5.5 combined with serum KL6 could be helpful for RA-ILD assessment correlating with HRCT and disease severity. Serum KL6 combined with LUS is important new and potential prognostic factor predicting poor outcomes in RA-ILD. Further large-scale, multi-center, and prospective studies are needed to confirm these findings.

KEY POINTS

• Combination of the non-invasive, radiation-free LUS with a score < 5.5 and serum KL6 levels of 277.5 U/ml is recommended as prognostic tools for RA-ILD. • Easily obtainable tests such as serum KL-6, inflammatory markers, and LUS are sensitive for assessing RA-ILD and the risk of poor outcomes in patients with RA-ILD. • RA-ILD patients with higher KL6 levels, higher LUS scores had a poor prognosis with short survival. • LUS B lines could be used as the first imaging tool for the evaluation of RA-ILD decreasing the risk of HRCT radiation exposure in asymptomatic or mild RA-ILD patients.