Novel immunologic classification of aspergillosis in adult cystic fibrosis

Abstract

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-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, 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.

Keywords: ABPA; ABPA-S; Allergic bronchopulmonary aspergillosis; Aspergillus fumigatus; CF; CV; Coefficient of variation; Cystic fibrosis; GM; Galactomannan (a measure of Aspergillus growth); SPT; Serologic ABPA; Skin prick test; allergic bronchopulmonary aspergillosis; bronchitis; cystic fibrosis; galactomannan; polymerase chain reaction.