Novel immunologic classification of aspergillosis in adult cystic fibrosis

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• 作者：Caroline G. Baxter ; Graham Dunn ; Andrew M. Jones ; Kevin Webb ; Robin Gore ; Malcolm D. Richardson ; David W. Denning
• 关键词：Aspergillus fumigatus ; cystic fibrosis ; bronchitis ; allergic bronchopulmonary aspergillosis ; polymerase chain reaction ; galactomannan
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：132
• 期：3
• 页码：560-566.e10
• 全文大小：953 K

文摘

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Background

Patients with cystic fibrosis (CF) demonstrate a wide range of hypersensitivity responses to Aspergillus, beyond allergic bronchopulmonary aspergillosis, which require classification.

Objective

This study integrated 2 new methods of Aspergillus detection¡ªsputum galactomannan (GM) and real-time PCR¡ªalongside established serologic markers, to reclassify aspergillosis in CF.

Methods

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.

Results

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).

Conclusions

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.