Antifungal treatment in allergic bronchopulmonary aspergillosis with and without cystic fibrosis: a systematic review.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA.

Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization.

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.

Using rare diseases as models for biobehavioral research: allergic bronchopulmonary aspergillosis.

Biobehavioral science explores links between biological, psychosocial, and behavioral factors and health. Maintaining positive health outcomes over time and across a variety of populations and settings requires understanding interactions among biological, behavioral, and social risk factors as well as other variables that influence behavior. Some barriers to biobehavioral research are related to performing biobehavioral research along the natural history of an illness, limitations in existing methodologies to assess the biological impact of behavior, the unknowns relating to impact of behavior on biology, and lack of valid and reliable biobehavioral methods to assess outcomes. A rare disease, such as allergic bronchopulmonary aspergillosis (ABPA) can be used as a model of biobehavioral research. ABPA complicates asthma and cystic fibrosis. It is a hypersensitivity reaction to Aspergillus fumigatus in most cases. ABPA can be classified into five stages: acute, remission, exacerbation, steroid-dependent asthma, and fibrotic or end stage. Because of its rarity, there can be delays in diagnosis. Treatment has used oral corticosteroids and antifungal agents in addition to management of asthma or cystic fibrosis. The National Institute of Nursing Research held an invitational 2-day working group meeting on July 15-16, 2004 with biobehavioral, biological, and immunologic science experts to examine current knowledge of biobehavioral research and to provide recommendations for additional research. The focus was on biobehavioral methods of measurement and analysis with interdisciplinary/biobehavioral approaches. This article is an outcome of this meeting.