Respiratory Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
BMC Infect Dis. 2018 Jun 11;18(1):271. doi: 10.1186/s12879-018-3180-z.
Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied.
This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models.
We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD.
This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.
患有基础呼吸系统疾病（URD）的患者中，侵袭性肺曲霉病（IPA）的报道日益增多。IPA 的早期诊断对于降低死亡率和改善预后至关重要，但仍存在困难。IPA 的现有诊断工具主要依赖于基于血清或支气管肺泡灌洗液（BALF）的生物标志物检测，这两者都有其局限性。痰液样本的使用具有非侵入性，并且可以检测到曲霉属；然而，痰液生物标志物对 IPA 的诊断价值，特别是在 URD 患者中的诊断价值，尚未得到系统研究。
这是一项前瞻性诊断试验。将从呼吸病房和重症监护病房招募至少 118 名参与者。根据改良的 EORTC/MSG 标准定义 IPA，适用于 URD 患者。通过支气管镜获取诱导痰和血液，并获取 BALF。测定痰液生物标志物，包括半乳甘露聚糖、曲霉属 DNA、三乙酰基交链孢酚和双（甲基硫代）Gliotoxin，并使用侧向液流装置检查 JF5 抗原的存在。将计算不同生物标志物的敏感性、特异性、阴性预测值、阳性预测值和诊断优势比，并使用 McNemar χ 检验进行比较。将进行接收者操作特征分析，并确定截断值。参与者将在招募后 3 个月和 6 个月接受随访评估。将分析住院时间和生存率的差异，并通过回归模型分析生物标志物水平与住院时间和生存率的关系。
我们已经开发并验证了用于痰液的曲霉属相关生物标志物检测的可行性。研究结果将为痰液生物标志物在 IPA 中的诊断性能提供新的视角，并为改善 IPA 的早期诊断提供重要见解，特别是在 URD 患者中。
本研究于 2016 年 8 月 24 日在中国临床试验注册中心（ChiCTR-DPD-16009070）注册。
