结缔组织病相关间质性肺疾病的临床相关生物标志物

Clinically Relevant Biomarkers of Interstitial Lung Disease Associated with Connective Tissue Diseases

摘要: 间质性肺病(ILD)是结缔组织病(CTD)的一种常见表现，最常影响类风湿关节炎(RA)、系统性硬化症(SSc)、特发性炎性肌病(IIM)和混合性CTD患者。间质性肺病也可发生在Sjögren综合征(SS)和系统性红斑狼疮患者中，但在这些疾病中较少见。在发展为CTD-ILD的患者中，一个亚群将发展为进行性表型，导致实质破坏、肺功能下降和早期死亡。早期和准确的诊断对于有效管理CTD-ILD患者至关重要，特别是因为已有有效的治疗方法可以稳定疾病，有时还可以改善患者肺功能。诊断ILD往往是微妙而困难的，因为许多CTD-ILD患者没有呼吸道症状，即使出现症状也是非特异性的。肺功能测试(PFT)可以帮助CTD患者检测是否合并ILD，但测试表现特征一般。一旦ILD被诊断出来，无法区分可能进展的患者仍然是难以捉摸的。临床预测模型已被开发用于预测CTD患者的ILD进展，但许多模型是针对CTD的，这降低了对更大的CTD-ILD人群的泛化性。预测CTD-ILD进展的能力将使患者和临床医生能够在治疗、肺移植和护理目标方面做出更明智的决定。生物标志物被定义为正常生物过程和致病过程的指标，有望提高我们准确诊断ILD和预测疾病轨迹的能力。理想的生物标志物应该是非侵入性或微创性的，在预测终点方面具有很高的准确性。最有可能为CTD患者的临床决策提供信息的生物标志物是那些在出现呼吸道症状和进行性表型之前预测早期疾病的生物标志物。在过去的十年中，许多研究已经确定了候选的基于血液和高分辨率计算机断层扫描(HRCT)的生物标志物，最近的组学研究已经将复合生物标志物添加到CTD-ILD人群中潜在的临床相关生物标志物列表中。然而，临床实施的障碍仍然存在。本文综述了CTD-ILD生物标志物研究的最新进展，重点是血液和HRCT生物标志物，并重点介绍了在CTD-ILD患者中推进这些生物标志物临床应用的策略。

Abstract: Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD), most frequently affecting patients with rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), and mixed CTD. Interstitial lung disease can also occur in patients with Sjogren’s syndrome (SS) and systemic lupus erythematosus, but it is less common in these diseases. Among patients developing CTD-ILD, a subpopulation will progress to a progressive phenotype, leading to parenchymal destruction, decreased lung function and early death. Early and accurate diagnosis is crucial for the effective management of CTD-ILD patients, especially since there are already effective treatment methods that can stabilize the disease and sometimes improve the lung function of patients. Diagnosing ILD is often subtle and difficult because many CTD-ILD patients have no respiratory symptoms, and even if symptoms occur, they are non-specific. Pulmonary function tests (PFT) can help CTD patients detect whether they have ILD, but the test results are generally characterized. Once ILD is diagnosed, patients who cannot distinguish possible progression remain elusive. Clinical predictive models have been developed to predict the progression of ILD in CTD patients, but many of these models are targeted at CTD, which reduces the generalization for the larger CTD-ILD population. The ability to predict the progression of CTD-ILD will enable patients and clinicians to make more informed decisions regarding treatment, lung transplantation and care goals. Biomarkers are defined as indicators of normal biological processes and pathogenic processes, and are expected to enhance our ability to accurately diagnose ILD and predict disease trajectories. The ideal biomarker should be non-invasive or minimally invasive and have high accuracy in predicting endpoints. The biomarkers most likely to inform the clinical decision-making of CTD patients are those that predict early disease before the appearance of respiratory symptoms and progressive phenotypes. Over the past decade, many studies have identified candidate biomarkers based on blood and high-resolution computed tomography (HRCT), and recent omics studies have added composite biomarkers to the list of potential clinically relevant biomarkers in the CTD-ILD population. However, obstacles to clinical implementation still exist. This article reviews the latest progress in the research of CTD-ILD biomarkers, with a focus on blood and HRCT biomarkers, and particularly introduces the strategies for promoting the clinical application of these biomarkers in CTD-ILD patients.