Electronic Nose Technology for Detection of Invasive Pulmonary Aspergillosis in Prolonged Chemotherapy-Induced Neutropenia: a Proof-of-Principle Study

Electronic Nose Technology for Detection of Invasive Pulmonary Aspergillosis in Prolonged Chemotherapy-Induced Neutropenia: a Proof-of-Principle Study
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DOI:
10.1128/jcm.02838-12
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发表时间:
2013-05-01
影响因子:
9.4
通讯作者:
Sterk, Peter J.
Sterk, Peter J.
中科院分区:
医学2区
文献类型:
--
作者:
de Heer, Koen;van der Schee, Marc P.;Sterk, Peter J.

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虽然及时诊断可降低长期化疗所致中性粒细胞减少症(PCIN)患者肺部侵袭性曲霉病(IA)的高死亡率,但缺乏可靠的早期检测IA的诊断试验。我们假设电子鼻可以满足这一需求。电子鼻可以通过对呼出的挥发性有机化合物(VOCs)的分析来区分各种肺部疾病。鼻腔注射是一种廉价、非侵入性的方法,在几分钟内就能产生结果。在一项单中心前瞻性队列研究中,我们纳入了接受化疗的患者,这些患者预计会导致PCIN。根据标准化的适应症,进行了全面的诊断检查,以确认或排除侵袭性曲霉病。没有曲霉病的患者被认为是对照,而可能有或证实有曲霉病的患者被认为是指示病例。呼出的呼吸用Cyranose 320(Smith Detections,加利福尼亚州帕萨迪纳市)检查。使用主成分约简法对所得数据进行分析。主要终点是交叉验证的诊断准确性,定义为使用留一法正确分类的患者的百分比。通过100,000个随机分类验证了准确性。我们包括46名受试者,他们接受了16次诊断检查,结果是6例病例和5名对照。交叉验证诊断IA的准确率为90.9%(P=0.022;敏感性100%;特异性83.3%)。接收器工作特性分析显示曲线下面积为0.93。这些初步数据表明,患有IA的PCIN患者有明显的呼出VOC谱,可以用ENOSE技术检测到。鼻腔鼻对侵袭性曲霉病的诊断准确性值得验证。
Although the high mortality rate of pulmonary invasive aspergillosis (IA) in patients with prolonged chemotherapy-induced neutropenia (PCIN) can be reduced by timely diagnosis, a diagnostic test that reliably detects IA at an early stage is lacking. We hypothesized that an electronic nose (eNose) could fulfill this need. An eNose can discriminate various lung diseases through the analysis of exhaled volatile organic compounds (VOCs). An eNose is cheap and noninvasive and yields results within minutes. In a single-center prospective cohort study, we included patients who were treated with chemotherapy expected to result in PCIN. Based on standardized indications, a full diagnostic workup was performed to confirm invasive aspergillosis or to rule it out. Patients with no aspergillosis were considered controls, and patients with probable or proven aspergillosis were considered index cases. Exhaled breath was examined with a Cyranose 320 (Smith Detections, Pasadena, CA). The resulting data were analyzed using principal component reduction. The primary endpoint was cross-validated diagnostic accuracy, defined as the percentage of patients correctly classified using the leave-one-out method. Accuracy was validated by 100,000 random classifications. We included 46 subjects who underwent 16 diagnostic workups, resulting in 6 cases and 5 controls. The cross-validated accuracy of the eNose in diagnosing IA was 90.9% (P = 0.022; sensitivity, 100%; specificity, 83.3%). Receiver operating characteristic analysis showed an area under the curve of 0.93. These preliminary data indicate that PCIN patients with IA have a distinct exhaled VOC profile that can be detected with eNose technology. The diagnostic accuracy of the eNose for invasive aspergillosis warrants validation.