Salzer Helmut J F, Prattes Juergen, Flick Holger, Reimann Maja, Heyckendorf Jan, Kalsdorf Barbara, Obersteiner Sabrina, Gaede Karoline I, Herzmann Christian, Johnson Gemma L, Lange Christoph, Hoenigl Martin
Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany.
German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel, Borstel, Germany.
Front Microbiol. 2018 Oct 2;9:2223. doi: 10.3389/fmicb.2018.02223. eCollection 2018.
Diagnosis of chronic pulmonary aspergillosis (CPA) is challenging. Symptoms are unspecific or missing, radiological findings are variable and proof of mycological evidence is limited by the accuracy of diagnostic tests. The goal of this study was to investigate diagnostic performance of galactomannan (GM), the newly formatted -specific lateral-flow-device test (LFD), and a number of cytokines in bronchoalveolar lavage fluid (BALF) samples obtained from patients with CPA, patients with respiratory disorders without CPA and healthy individuals. Patients with CPA ( = 27) and controls ( = 27 with underlying respiratory diseases but without CPA, and = 27 healthy volunteers) were recruited at the Medical University of Graz, Austria and the Research Center Borstel, Germany between 2010 and 2018. GM, LFD and cytokine testing was performed retrospectively at the Research Center Borstel. Sensitivity and specificity of GM testing from BALF with a cut off level of ≥0.5 optical density index (ODI) was 41 and 100% and 30 and 100% with a cut off level of ≥1.0 ODI. ROC curve analysis showed an AUC 0.718 (95% CI 0.581-0.855) for GM for differentiating CPA patients to patients with other respiratory diseases without CPA. The LFD resulted positive in only three patients with CPA (7%) and was highly specific. CPA patients did not differ significantly in the BALF cytokine profile compared to patients with respiratory disorders without CPA, but showed significant higher values for IFN-γ, IL-1b, IL-6, IL-8, and TNF-α compared to healthy individuals. Both GM and LFD showed insufficient performance for diagnosing CPA, with sensitivities of BALF GM below 50%, and sensitivity of the LFD below 10%. The high specificities may, however, result in a high positive predictive value and thereby help to identify semi-invasive or invasive disease.
慢性肺曲霉病（CPA）的诊断具有挑战性。症状不具特异性或不存在，影像学表现多样，且真菌学证据的证明受到诊断测试准确性的限制。本研究的目的是调查半乳甘露聚糖（GM）、新形式的特异性侧向流动装置测试（LFD）以及从CPA患者、无CPA的呼吸系统疾病患者和健康个体获得的支气管肺泡灌洗（BALF）样本中的多种细胞因子的诊断性能。2010年至2018年期间，在奥地利格拉茨医科大学和德国博尔斯特尔研究中心招募了CPA患者（n = 27）和对照组（n = 27例有潜在呼吸系统疾病但无CPA的患者，以及n = 27名健康志愿者）。GM、LFD和细胞因子检测在博尔斯特尔研究中心进行回顾性分析。BALF中GM检测的灵敏度和特异性，截断水平≥0.5光密度指数（ODI）时分别为41%和100%，截断水平≥1.0 ODI时分别为30%和100%。ROC曲线分析显示，GM区分CPA患者与无CPA的其他呼吸系统疾病患者的AUC为0.718（95%CI 0.581 - 0.855）。LFD仅在3例CPA患者中呈阳性（7%），且具有高度特异性。与无CPA的呼吸系统疾病患者相比，CPA患者的BALF细胞因子谱无显著差异，但与健康个体相比，IFN-γ、IL-1b、IL-6、IL-8和TNF-α的值显著更高。GM和LFD在诊断CPA方面均表现不佳，BALF中GM的灵敏度低于50%，LFD的灵敏度低于10%。然而，高特异性可能导致高阳性预测值，从而有助于识别半侵袭性或侵袭性疾病。
