title: IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma.
abstract: BACKGROUND
  The importance of Aspergillus fumigatus sensitization and colonization of the airways in patients with asthma is unclear.
  
  
  OBJECTIVE
  To define the relationship between the clinical and laboratory features of A. fumigatus-associated asthma.
  
  
  METHODS
  We studied 79 patients with asthma (89% classed as GINA 4 or 5) classified into 3 groups according to A. fumigatus sensitization: (1) IgE-sensitized (immediate cutaneous reactivity > 3 mm and/or IgE > 0.35 kU/L); (2) IgG-only-sensitized (IgG > 40 mg/L); and (3) nonsensitized. These were compared with 14 healthy control subjects. Sputum culture was focused toward detection of A. fumigatus and compared with clinical assessment data.
  
  
  RESULTS
  A. fumigatus was cultured from 63% of IgE-sensitized patients with asthma (n = 40), 39% of IgG-only-sensitized patients with asthma (n = 13), 31% of nonsensitized patients with asthma (n = 26) and 7% of healthy control subjects (n = 14). Patients sensitized to A. fumigatus compared with nonsensitized patients with asthma had lower lung function (postbronchodilator FEV₁ % predicted, mean [SEM]: 68 [±5]% versus 88 [±5]%; P < 0.05), more bronchiectasis (68% versus 35%; P < 0.05), and more sputum neutrophils (median [interquartile range]: 80.9 [50.1-94.1]% versus 49.5 [21.2-71.4]%; P < 0.01). In a multilinear regression model, A. fumigatus-IgE sensitization and sputum neutrophil differential cell count were important predictors of lung function (P = 0.016), supported by culture of A. fumigatus (P = 0.046) and eosinophil differential cell count (P = 0.024).
  
  
  CONCLUSIONS
  A. fumigatus detection in sputum is associated with A. fumigatus-IgE sensitization, neutrophilic airway inflammation, and reduced lung function. This supports the concept that development of fixed airflow obstruction in asthma is consequent upon the damaging effects of airway colonization with A. fumigatus.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Glenfield Hospital, UK.
authors.forename: Abbie
authors.initials: A
authors.lastname: Fairs
authors.forename: Joshua
authors.initials: J
authors.lastname: Agbetile
authors.forename: Beverley
authors.initials: B
authors.lastname: Hargadon
authors.forename: Michelle
authors.initials: M
authors.lastname: Bourne
authors.forename: William R
authors.initials: WR
authors.lastname: Monteiro
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Green
authors.forename: Kugathasan
authors.initials: K
authors.lastname: Mutalithas
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Desai
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wardlaw
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Pashley
mesh_terms: D000328:Adult; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D001987:Bronchiectasis / Q000209:etiology / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D012129:Respiratory Function Tests / Q000379:methods; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology
chemical_list: D007073:Immunoglobulin E