Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, Netherlands.
Lancet Respir Med. 2015 Apr;3(4):290-300. doi: 10.1016/S2213-2600(15)00050-8. Epub 2015 Mar 20.
Eosinophilic airway inflammation is associated with increased corticosteroid responsiveness in asthma, but direct airway sampling methods are invasive or laborious. Minimally invasive markers for airway eosinophilia could present an alternative method, but estimates of their accuracy vary.
We did a systematic review and searched Medline, Embase, and PubMed for studies assessing the diagnostic accuracy of markers against a reference standard of induced sputum, bronchoalveolar lavage, or endobronchial biopsy in patients with asthma or suspected asthma (for inception to Aug 1, 2014). Unpublished results were obtained by contacting authors of studies that did not report on diagnostic accuracy, but had data from which estimates could be calculated. We assessed risk of bias with QUADAS-2. We used meta-analysis to produce summary estimates of accuracy.
We included 32 studies: 24 in adults and eight in children. Of these, 26 (81%) showed risk of bias in at least one domain. In adults, three markers had extensively been investigated: fraction of exhaled nitric oxide (FeNO) (17 studies; 3216 patients; summary area under the receiver operator curve [AUC] 0·75 [95% CI 0·72-0·78]); blood eosinophils (14 studies; 2405 patients; 0·78 [0·74-0·82]); total IgE (seven studies; 942 patients; 0·65 [0·61-0·69]). In children, only FeNO (six studies; 349 patients; summary AUC 0·81 [0·72-0·89]) and blood eosinophils (three studies; 192 patients; 0·78 [0·71-0·85]) had been investigated in more than one study. Induced sputum was most frequently used as the reference standard. Summary estimates of sensitivity and specificity in detecting sputum eosinophils of 3% or more in adults were: 0·66 (0·57-0·75) and 0·76 (0·65-0·85) for FeNO; 0·71 (0·65-0·76) and 0·77 (0·70-0·83) for blood eosinophils; and 0·64 (0·42-0·81) and 0·71 (0·42-0·89) for IgE.
FeNO, blood eosinophils, and IgE have moderate diagnostic accuracy. Their use as a single surrogate marker for airway eosinophilia in patients with asthma will lead to a substantial number of false positives or false negatives.
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嗜酸性气道炎症与哮喘中皮质激素反应性增加有关，但直接气道采样方法具有侵袭性或繁琐。气道嗜酸性粒细胞的微创标志物可能提供一种替代方法，但对其准确性的评估各不相同。
我们进行了系统评价，并在 Medline、Embase 和 PubMed 中搜索了评估哮喘或疑似哮喘患者（截至 2014 年 8 月 1 日）诱导痰、支气管肺泡灌洗或支气管内膜活检参考标准的标志物诊断准确性的研究。通过联系未报告诊断准确性但有可计算估计值的数据的研究作者，获得了未发表的结果。我们使用 QUADAS-2 评估了偏倚风险。我们使用荟萃分析产生了准确性的综合估计值。
我们纳入了 32 项研究：24 项在成人中进行，8 项在儿童中进行。其中，26 项（81%）在至少一个领域存在偏倚风险。在成人中，有三种标志物已得到广泛研究：呼出气一氧化氮分数（FeNO）（17 项研究；3216 例患者；汇总受试者工作特征曲线下面积[AUC]0·75[95%CI 0·72-0·78]）、血嗜酸性粒细胞（14 项研究；2405 例患者；0·78[0·74-0·82]）和总 IgE（7 项研究；942 例患者；0·65[0·61-0·69]）。在儿童中，只有 FeNO（6 项研究；349 例患者；汇总 AUC 0·81[0·72-0·89]）和血嗜酸性粒细胞（3 项研究；192 例患者；0·78[0·71-0·85]）在一项以上研究中进行了研究。诱导痰最常被用作参考标准。在检测成人痰嗜酸性粒细胞 3%或更多方面的敏感性和特异性的汇总估计值为：FeNO 为 0·66（0·57-0·75）和 0·76（0·65-0·85）；血嗜酸性粒细胞为 0·71（0·65-0·76）和 0·77（0·70-0·83）；IgE 为 0·64（0·42-0·81）和 0·71（0·42-0·89）。
FeNO、血嗜酸性粒细胞和 IgE 具有中等诊断准确性。将其作为哮喘患者气道嗜酸性粒细胞的单一替代标志物使用，将导致大量假阳性或假阴性。
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