National Aspergillosis Centre, University Hospital of South Manchester, Manchester, United Kingdom; Manchester Adult Cystic Fibrosis Centre, University Hospital of South Manchester, Manchester, United Kingdom; The University of Manchester and the Manchester Academic Health Science Centre, Manchester, United Kingdom.
Health Sciences Methodology, School of Community Based Medicine, University of Manchester, Manchester, United Kingdom.
J Allergy Clin Immunol. 2013 Sep;132(3):560-566.e10. doi: 10.1016/j.jaci.2013.04.007. Epub 2013 May 29.
Patients with cystic fibrosis (CF) demonstrate a wide range of hypersensitivity responses to Aspergillus, beyond allergic bronchopulmonary aspergillosis, which require classification.
This study integrated 2 new methods of Aspergillus detection-sputum galactomannan (GM) and real-time PCR-alongside established serologic markers, to reclassify aspergillosis in CF.
A total of 146 adult patients with CF had serologic tests (ImmunoCap total IgE, specific Aspergillus fumigatus IgE, and specific A fumigatus IgG), sputum real-time Aspergillus PCR, and sputum GM. Patients were classified by using latent class analysis.
Both RT-PCR and GM were more sensitive than culture in detecting Aspergillus in sputum (culture 37%, RT-PCR 74%, and GM 46%). Intraassay and interassay reproducibility of PCR and GM was excellent. Latent class analysis of triazole-naive patients identified a nondiseased group and 3 disease classes: class 1 (n = 49, 37.7%) represented patients with or without positive RT-PCR but no immunologic response to A fumigatus and negative GM (nondiseased); class 2 (n = 23, 17.7%) represented patients with positive RT-PCR, elevated total and specific A fumigatus IgE/IgG, and positive GM (serologic allergic bronchopulmonary aspergillosis); class 3 (n = 19, 14.6%) represented patients with or without positive RT-PCR, elevated A fumigatus IgE (not IgG), and negative GM (Aspergillus sensitized); and class 4 (n = 39, 30%) represented patients with positive RT-PCR, elevated A fumigatus IgG (not IgE), and positive GM (Aspergillus bronchitis).
Three distinct classes of aspergillosis in CF were identified by latent class analysis by using serologic, RT-PCR, and GM data. This novel classification will facilitate improved phenotyping, pathogenesis studies, and management evaluations.
囊性纤维化（CF）患者对烟曲霉表现出广泛的超敏反应，超出了变应性支气管肺曲霉病的范围，需要进行分类。
本研究整合了两种新的烟曲霉检测方法——痰半乳甘露聚糖（GM）和实时 PCR——以及已建立的血清学标志物，对 CF 中的曲霉病进行再分类。
共对 146 例成年 CF 患者进行了血清学检测（免疫捕获总 IgE、特异性烟曲霉 IgE 和特异性 A fumigatus IgG）、痰实时曲霉 PCR 和痰 GM。使用潜在类别分析对患者进行分类。
RT-PCR 和 GM 在检测痰中的曲霉时均比培养更敏感（培养 37%，RT-PCR 74%，GM 46%）。PCR 和 GM 的室内和室间重复性均极佳。未接受三唑类药物治疗的患者的潜在类别分析确定了一个非疾病组和 3 个疾病组：第 1 类（n=49，37.7%）代表 RT-PCR 阳性但无烟曲霉免疫反应且 GM 阴性的患者（非疾病）；第 2 类（n=23，17.7%）代表 RT-PCR 阳性、总和特异性烟曲霉 IgE/IgG 升高且 GM 阳性的患者（变应性支气管肺曲霉病）；第 3 类（n=19，14.6%）代表 RT-PCR 阳性、烟曲霉 IgE 升高（而非 IgG）且 GM 阴性的患者（烟曲霉致敏）；第 4 类（n=39，30%）代表 RT-PCR 阳性、烟曲霉 IgG 升高（而非 IgE）且 GM 阳性的患者（曲霉性支气管炎）。
通过使用血清学、RT-PCR 和 GM 数据进行潜在类别分析，CF 中鉴定出了 3 种不同类别的曲霉病。这种新的分类方法将有助于改善表型、发病机制研究和管理评估。
