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Interferon gamma replacement as salvage therapy in chronic pulmonary aspergillosis: effects on frequency of acute exacerbation and all-cause hospital admission
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  1. Edward J M Monk1,
  2. Chris Harris1,2,
  3. Rainer Döffinger3,
  4. Gemma Hayes4,
  5. David W Denning1,2,
  6. Chris Kosmidis1,2
  1. 1 National Aspergillosis Centre, Manchester University NHS Foundation Trust, Manchester, UK
  2. 2 Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
  3. 3 Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  4. 4 Department of Respiratory Medicine, Derriford Hospital, University Hospitals Plymouth NHS Trust, Plymouth, UK
  1. Correspondence to Dr Chris Kosmidis, National Aspergillosis Centre, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK; chris.kosmidis{at}manchester.ac.uk

Abstract

Chronic pulmonary aspergillosis (CPA) is often poorly responsive to antifungal treatment; secondary infections increase morbidity/mortality, particularly in progressive cases. Interferon gamma (IFNγ) has been implicated in not only Aspergillus control but also bacterial clearance. Clinical notes of patients with CPA treated with IFNγ (2011–2018) were retrospectively hand-searched. In patients treated for >12 months (n=20), the frequency of acute exacerbation reduced from 3.1 to 1.4 episodes/year (p=0.006) in the 12 months after treatment initiation compared with the 12 months before. A significant reduction in the frequency of hospital admissions/year was also observed (0.8 to 0.3, p=0.04). These findings support further prospective studies.

  • aspergillus lung disease
  • immunodeficiency
  • respiratory infection

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Footnotes

  • Contributors CK: conceived the project. RD: coordinated and interpreted immunodeficiency testing. CH and CK: performed the patient search. EJMM and CK: performed data collection; analysed and interpreted the data; drafted the manuscript. CH, RD, GH and DWD: critically revised the manuscript for intellectual content. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DWD and family hold Founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company. He acts or has recently acted as a consultant to Scynexis, Cidara, Pulmatrix, Zambon, iCo Therapeutics, Roivant and Fujifilm. In the last 3 years, he has been paid for talks on behalf of Dynamiker, Hikma, Gilead, Merck, Mylan and Pfizer. He is a longstanding member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group and the British Society for Medical Mycology Standards of Care committee.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.