Novel immunologic classification of aspergillosis in adult cystic fibrosis - 02/09/13
, Graham Dunn, PhD d, Andrew M. Jones, MD b, c, Kevin Webb, MD b, c, Robin Gore, PhD c, Malcolm D. Richardson, PhD a, c, David W. Denning, MD a, cAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Aspergillus fumigatus, cystic fibrosis, bronchitis, allergic bronchopulmonary aspergillosis, polymerase chain reaction, galactomannan
Abbreviations used : ABPA, CF, CV, GM, ABPA-S, SPT
Plan
| This study was supported by the National Commissioning Group, National Aspergillosis Centre, University Hospital of South Manchester, United Kingdom. |
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| Disclosure of potential conflict of interest: C. G. Baxter has received one or more payments for lecturing from or is on the speakers’ bureau for Astellas and has received one or more payments for travel/accommodations/meeting expenses from Schering Plough, Pfizer, and Merck. D. W. Denning holds founder shares in F2G Ltd, a University of Manchester spin-out company; has received grant support from F2G, the Fungal Research Trust, the Wellcome Trust, the Moulton Trust, The Medical Research Council, The Chronic Granulomatous Disease Research Trust, the National Institute of Allergy and Infectious Diseases, National Institute of Health Research, the European Union, and AstraZeneca; has acted as an advisor/consultant to F2G and Myconostica (now part of the Lab21 group) as well as other companies over the last 5 years including Pfizer, T2Biosystems, Schering Plough (now Merck), Nektar, Astellas, and Gilead; and has been paid for talks on behalf of Merck, Gilead Sciences, Astellas, Novartis, Merck, Dainippon, and Pfizer. M. D. Richardson acts as an advisor/consultant to Astellas Pharma, Merck, and Gilead Sciences and has received grant support and sponsorship from these companies; has consultancy arrangements with and has received one or more payments for the development of educational presentations for Gilead Sciences, Astellas Pharma, and Merck; has received one or more grants from or has one or more grants pending with Gilead Sciences and Astellas; has received one or more payments for lecturing from or is on the speakers’ bureau for Gilead Sciences, Astellas, and MSD; and has received royalties from Wiley-Blackwell. G. Dunn has received MRC and NIHR research grants and textbook royalties. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 3
P. 560 - septembre 2013 Retour au numéro
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