Proponents of antifungals for the treatment of CRS and AFS argue that in CRS, fungi in sinonasal mucosa cause the activation of sensitized patients' immune systems, thereby driving the eosinophilic inflammation. Consequently, eliminating fungus in the sinus and nasal cavity through the use of antifungals would potentially reduce this inflammatory response.3
There is no evidence of any benefit of topical antifungals from the included studies. Topical antifungal therapy reported beneficial effects in only one of five trials38
for radiographic and endoscopic scores, but not for symptoms. There was substantial heterogeneity in these two outcomes, possibly because of differences in patient populations and disease factors. The control groups were favored in one of five trials40,42–44
for symptom scores and disease-specific quality-of-life scores. The pooled results showed significant symptom improvement in the placebo group across those studies reporting this outcome.
The five studies differed in methodology. Delivery volume and surgical state are established factors influencing the effectiveness to topical delivery to the sinuses.42–44
Three trials used nasal irrigation35,37,38
and two trials used nasal sprays36,40
to administer the antifungal or placebo. Patients who had endoscopic sinus surgery (ESS) were reported heterogeneously. Some trials required patients to have had previous ESS before administration of the antifungal or placebo35,36
and other trials had some patients who had not had previous ESSs.38,40
In one trial, previous ESS was part of the exclusion criteria and therefore no patients had previous ESSs.37
Although traditional concepts of ESS is aimed at relieving obstruction and improving ventilation, ESS has been shown to allow effective delivery of topical therapies to the mucosa of the sinuses compared with the preoperative state.42,43
The concentrations of the antifungal differed among studies. This may influence the proposed action because fungal growth may not be impeded at a concentration of 100 μg/mL in vitro
compared with convincing inhibition at 200 and 300 μg/mL.45
Two trials used amphotericin B at concentrations of 100 μg/mL.35,36
There is currently some controversy surrounding both the optimum dosage and the preparation of the antifungal treatment, which may influence the ultimate outcome of treatment.
Systemic antifungal therapy reported no benefits over placebo for symptom scores or radiographic scores. Because there was only one trial that fit our inclusion criteria for systemic antifungals, there is no heterogeneity of approach.
Although it is well known that fungi are both ubiquitous in the sinuses and the environment and can therefore be found in normal sinuses, there are certain phenotypes of the disease process that may more readily yield positive culture or behave differently with regard to antifungal therapy. These situations might, in fact, represent a process where the fungi are causative and these specific situations may call for antifungal therapy to be used.
Although there was incomplete reporting of data in the published literature of the included studies, authors of four of the five topical antifungal RCTs provided original data to allow a meta-analysis.35,37,38,40
Some imputation and transformation was performed but original data provided limited this to only one study.36
The results of this meta-analysis confirms the conclusion from a previous nonsystematic review conducted by Lim et al.
which states that “no definite conclusions could be made regarding the use of antifungals.” Lim et al.
found 14 studies that fulfilled their inclusion criteria; however, only 7 studies were controlled trials and only 5 were double-blind randomized trials. Two of their RCTs were excluded in this review because they did not deal with antifungals as an intervention.47,48
Three more trials were included in this review.36,37,39
No meta-analysis was performed in the study by Lim et al.46
Rather, it was purely qualitative.