Voriconazole and Posaconazole Improve Asthma Severity in Allergic Bronchopulmonary Aspergillosis and Severe Asthma with Fungal Sensitization

Abstract

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.

• allergic fungal pulmonary disease
• Aspergillus
• asthma control
• fungal sensitization
• severe asthma
• treatment

Acknowledgements

The authors thank Mrs Julie Morris, medical statistics, University Hospital of South Manchester, Manchester, UK, for helping with statistics and Mr Paul Somerset, medical illustrations, University Hospital of South Manchester, Manchester, UK, for helping with formatting the image files.

Dr Livingstone Chishimba was involved in the conception and design of the study; acquisition, analysis, and interpretation of the data; and wrote the article. Dr Robert Niven was substantially involved in its revision prior to submission. Prof David Denning was involved in the conception and design of the study and substantial involvement in its revision prior to submission. John Cooley analyzed and interpreted the information.

Declaration of Interests

Dr Livingstone Chishimba has no conflict of interest to declare. Mr John Cooley has no conflicts of interest to declare. Dr Robert Niven has provided expert views on management of fungal associated asthma to Vectura as part of an advisory board. He has performed lectures at national and international education meetings supported by GSK, Novartis, Chiesi, and AZ. He has also received travel grants from Novartis, Boehringer, and GSK to attend international educational and academic meetings. Prof David Denning has received consulting fee and honorarium from Pfizer, Merck, Astellas, and Gilead. He has received support for travel to meetings from Gilead and Astellas. He also runs the Aspergillus Website (www.aspergillus.org.uk) which has been supported by Pfizer, Merck, Gilead, Astellas, and the NHS.