Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
J Breath Res. 2019 Jun 24;13(3):036015. doi: 10.1088/1752-7163/ab1284.
Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment.
We undertook a systematic review and meta-analysis to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non breath-based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment.
Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis.
353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22 ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I of 93.4% (p < 0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment.
The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role.
结节病是一种病因不明的慢性肉芽肿性疾病，其临床表现和预后存在差异。目前，人们越来越需要寻找非侵入性生物标志物，以区分不同的临床表型，识别那些有疾病进展风险的患者，并监测治疗反应。
我们进行了系统的回顾和荟萃分析，以评估基于呼吸的生物标志物在鉴别结节病与健康对照方面的效用，并评估其与临床实践中使用的其他非基于呼吸的生物标志物、影像学分期、疾病活动标志物和治疗反应之间的相关性。
2017 年 11 月，我们通过 PubMed、Ebsco、Embase 和 Web of Science 进行了电子检索，以捕获评估成人结节病患者基于呼吸的生物标志物的相关研究。
共筛选出 353 篇论文，其中 21 篇符合纳入标准，评估了 25 种不同的生物标志物以及呼气气体或冷凝物中的挥发性有机化合物。研究在参与者特征、采样和分析方法方面存在很大的异质性。结节病中升高的生物标志物包括 8-异前列腺素、一氧化碳、新蝶呤、TGF-β1、TNFα、CysLT 和几种金属元素，包括铬、硅和镍。三项探索挥发性有机化合物的研究能够将结节病与对照组区分开来。四项评估肺泡一氧化氮的研究的荟萃分析显示，结节病与健康对照组之间无显著差异（2.22 ppb；95% CI -0.83, 5.27），但观察到高度异质性，I²为 93.4%（p<0.001）。许多生物标志物与影像学分期、疾病活动标志物或治疗之间的相关性不一致或无统计学意义。
使用呼吸生物标志物诊断和监测结节病的证据仍然不确定，许多研究受到样本量小和缺乏标准化的限制。挥发性有机化合物显示出有希望的潜力，但需要进一步研究来评估它们的预后作用。
