title: 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.
authors.affiliation: Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
authors.forename: Livingstone
authors.initials: L
authors.lastname: Chishimba
authors.forename: Robert M
authors.initials: RM
authors.lastname: Niven
authors.forename: John
authors.initials: J
authors.lastname: Cooley
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D004363:Drug Utilization; D005260:Female; D006296:Health Services / Q000706:statistics & numerical data; D006801:Humans; D008172:Lung Diseases, Fungal / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D013902:Radiography, Thoracic; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012959:Socioeconomic Factors; D013147:Spirometry; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D065819:Voriconazole