Novel immunologic classification of aspergillosis in adult cystic fibrosis

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Abstract

Background:

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

Objective:

This study integrated 2 new methods ofAspergillusdetection—sputum galactomannan (GM) and real-time PCR—alongside established serologic markers, to reclassify aspergillosis in CF.

Methods:

A total of 146 adult patients with CF had serologic tests (ImmunoCap total IgE, specificAspergillus fumigatusIgE, and specificA fumigatusIgG), sputum real-timeAspergillusPCR, and sputum GM. Patients were classified by using latent class analysis.

Results:

Both RT-PCR and GM were more sensitive than culture in detectingAspergillusin 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 toA fumigatusand negative GM (nondiseased); class 2 (n = 23, 17.7%) represented patients with positive RT-PCR, elevated total and specificA fumigatusIgE/IgG, and positive GM (serologic allergic bronchopulmonary aspergillosis); class 3 (n = 19, 14.6%) represented patients with or without positive RT-PCR, elevatedA fumigatusIgE (not IgG), and negative GM (Aspergillussensitized); and class 4 (n = 39, 30%) represented patients with positive RT-PCR, elevatedA fumigatusIgG (not IgE), and positive GM (Aspergillusbronchitis).

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.

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