Caroline G Baxter1, Graham Dunn2, Andrew M Jones3, Kevin Webb3, Robin Gore4, Malcolm D Richardson5, David W Denning5. 1. 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. Electronic address: caroline.baxter@manchester.ac.uk. 2. Health Sciences Methodology, School of Community Based Medicine, University of Manchester, Manchester, United Kingdom. 3. 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. 4. The University of Manchester and the Manchester Academic Health Science Centre, Manchester, United Kingdom. 5. National Aspergillosis Centre, University Hospital of South Manchester, Manchester, United Kingdom; The University of Manchester and the Manchester Academic Health Science Centre, Manchester, United Kingdom.
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.
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.
Authors: M Noni; A Katelari; G Dimopoulos; S-E Doudounakis; C Tzoumaka-Bakoula; V Spoulou Journal: Eur J Clin Microbiol Infect Dis Date: 2015-08-30 Impact factor: 3.267
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Authors: Thomas F Patterson; George R Thompson; David W Denning; Jay A Fishman; Susan Hadley; Raoul Herbrecht; Dimitrios P Kontoyiannis; Kieren A Marr; Vicki A Morrison; M Hong Nguyen; Brahm H Segal; William J Steinbach; David A Stevens; Thomas J Walsh; John R Wingard; Jo-Anne H Young; John E Bennett Journal: Clin Infect Dis Date: 2016-06-29 Impact factor: 9.079