title: Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study).
abstract: BACKGROUND
  IgE sensitization to Aspergillus fumigatus and a positive sputum fungal culture result are common in patients with refractory asthma. It is not clear whether these patients would benefit from antifungal treatment.
  
  
  OBJECTIVE
  We sought to determine whether a 3-month course of voriconazole improved asthma-related outcomes in patients with asthma who are IgE sensitized to A fumigatus.
  
  
  METHODS
  Asthmatic patients who were IgE sensitized to A fumigatus with a history of at least 2 severe exacerbations in the previous 12 months were treated for 3 months with 200 mg of voriconazole twice daily, followed by observation for 9 months, in a double-blind, placebo-controlled, randomized design. Primary outcomes were improvement in quality of life at the end of the treatment period and a reduction in the number of severe exacerbations over the 12 months of the study.
  
  
  RESULTS
  Sixty-five patients were randomized. Fifty-nine patients started treatment (32 receiving voriconazole and 27 receiving placebo) and were included in an intention-to-treat analysis. Fifty-six patients took the full 3 months of medication. Between the voriconazole and placebo groups, there were no significant differences in the number of severe exacerbations (1.16 vs 1.41 per patient per year, respectively; mean difference, 0.25; 95% CI, 0.19-0.31), quality of life (change in Asthma Quality of Life Questionnaire score, 0.68 vs 0.88; mean difference between groups, 0.2; 95% CI, -0.05 to -0.11), or any of our secondary outcome measures.
  
  
  CONCLUSIONS
  We were unable to show a beneficial effect of 3 months of treatment with voriconazole in patients with moderate-to-severe asthma who were IgE sensitized to A fumigatus on either the rate of severe exacerbations, quality of life, or other markers of asthma control.
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Joshua
authors.initials: J
authors.lastname: Agbetile
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bourne
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Abbie
authors.initials: A
authors.lastname: Fairs
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Beverley
authors.initials: B
authors.lastname: Hargadon
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Desai
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Broad
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Morley
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Bradding
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Green
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Pranabashis
authors.initials: P
authors.lastname: Haldar
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Pashley
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.affiliation: Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, and the Department of Respiratory Medicine, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, United Kingdom. Electronic address: aw24@le.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wardlaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000502:physiology; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D065819:Voriconazole / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D007073:Immunoglobulin E; D065819:Voriconazole
keywords: Aspergillus fumigatus; Refractory; allergic bronchopulmonary aspergillosis; asthma; eosinophils; exacerbations; mold; quality of life; severe asthma with fungal sensitization; voriconazole