Physical Medicine, Rheumatology and Rehabilitation Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, 32511, Egypt.
Chest and Tuberculosis Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt.
Clin Rheumatol. 2021 Jul;40(7):2689-2697. doi: 10.1007/s10067-021-05585-y. Epub 2021 Jan 21.
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.
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.
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.
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.
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.
• 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.
类风湿关节炎（RA）相关间质性肺疾病（ILD）（RA-ILD）是一种严重的系统性 RA 表现，死亡率高，需要适当、准确和敏感的评估工具。
首先，评估 RA-ILD 患者血清 Krebs von den Lungen-6（KL-6）水平和肺部超声 B 线（LUS B 线）评分，并将其与高分辨率计算机断层扫描（HRCT）和肺功能检查（PFTs）评估的ILD严重程度相关联。其次，确定 LUS 和 KL-6 在 RA-ILD 评估和预后预测中的截断值。
一项病例对照研究纳入了 75 例 RA-ILD 患者和 75 例具有相同数量无 ILD 的 RA 患者。临床评估包括 DAS-28 和 PFTs、血清 KL-6 的实验室评估，采用乳胶增强免疫比浊法、半定量 CT 分级和 LUS B 线对 ILD 进行放射学评估。
RA-ILD 患者的血清 KL6 明显高于无 ILD 患者（1025.5 ± 419.6 比 237.5 ± 51.9，p ≤ 0.001）。血清 KL6 与 HRCT 和 LUS 评分呈正相关（r = 0.93，r = 0.97），与 FVC%和 FEV1%呈负相关（r = -0.93，r = -0.91）。LUS 与 KL6 和 HRCT 呈正相关（r = 0.97，r = 0.944），与 PFTs 呈负相关。KL6 和 LUS 的截断值分别为 277.5 U/ml 和<5.5，其 AUC 分别为 0.878 和 1，灵敏度分别为 86.7%和 100%，特异性分别为 88%和 100%。
非侵入性、无辐射的 LUS 评分<5.5 结合血清 KL6 可能有助于评估 RA-ILD，与 HRCT 和疾病严重程度相关。血清 KL6 联合 LUS 是评估 RA-ILD 并预测 RA-ILD 患者不良结局的重要新的潜在预后因素。需要进一步的大规模、多中心和前瞻性研究来证实这些发现。
建议将非侵入性、无辐射的 LUS 评分<5.5 与血清 KL6 水平 277.5 U/ml 联合作为 RA-ILD 的预后工具。
易于获得的检测指标，如血清 KL-6、炎症标志物和 LUS，可用于敏感评估 RA-ILD 以及 RA-ILD 患者不良预后的风险。
RA-ILD 患者血清 KL6 水平较高、LUS 评分较高者预后不良，生存期较短。
LUS B 线可作为评估 RA-ILD 的首选影像学工具，减少无症状或轻度 RA-ILD 患者 HRCT 辐射暴露的风险。
