title: 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.
authors.affiliation: 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.
authors.forename: Caroline G
authors.initials: CG
authors.lastname: Baxter
authors.affiliation: Health Sciences Methodology, School of Community Based Medicine, University of Manchester, Manchester, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Dunn
authors.affiliation: 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.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Kevin
authors.initials: K
authors.lastname: Webb
authors.affiliation: The University of Manchester and the Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Robin
authors.initials: R
authors.lastname: Gore
authors.affiliation: 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.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Richardson
authors.affiliation: 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.
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000908:Antibodies, Fungal / Q000097:blood; D000946:Antigens, Fungal / Q000032:analysis; D001228:Aspergillosis / Q000145:classification* / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008351:Mannans / Q000032:analysis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012882:Skin Tests; D013183:Sputum / Q000737:chemistry; D055815:Young Adult
chemical_list: D000485:Allergens; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D007074:Immunoglobulin G; D008351:Mannans; C012990:galactomannan; D007073:Immunoglobulin E; D005690:Galactose
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