Abstract: We included eight studies (490 adult participants). The presence of nasal polyps on examination was an inclusion criterion in three studies, an exclusion criterion in one study and the remaining studies included a mixed population. No studies specifically investigated the effect of antifungals in patients with AFRS. Topical antifungal treatment versus placebo or no intervention We included seven studies (437 participants) that used amphotericin B (six studies; 383 participants) and one that used fluconazole (54 participants). Different delivery methods, volumes and concentrations were used. Four studies reported disease-specific health-related quality of life  using a range of instruments. We did not meta-analyse the results due to differences in the instruments used, and measurement and reporting methods. At the end of treatment (one to six months) none of the studies reported statistically significant differences between the groups (low-quality evidence - we are uncertain about the result). Two studies reported disease severity  using patient-reported symptom scores. Meta-analysis was not possible. At the end of treatment (8 to 13 weeks) one study showed no difference and the second found that patients in the placebo group had less severe symptoms (very low-quality evidence - we are very uncertain about the result). In terms of adverse effects , topical antifungals may lead to more local irritation compared with placebo (risk ratio (RR) 2.29, 95% confidence interval (CI) 0.61 to 8.62; 312 participants; 5 studies; low-quality evidence) but little or no difference in epistaxis (RR 0.97, 95% CI 0.14 to 6.63; 225 participants; 4 studies, low-quality evidence) or headache (RR 1.26, 95% CI 0.60 to 2.63; 195 participants; 3 studies; very low-quality evidence). None of the studies found a difference in generic health-related quality of life  (one study) or endoscopic score  (five studies) between the treatment groups. Three studies investigated CT scan ; two found no difference between the groups and one found a significant decrease in the mean percentage of air space occluded, favouring the antifungal group. Systemic antifungal treatment versus placebo or no treatment One study (53 participants) comparing terbinafine tablets against placebo reported that there may be little or no difference between the groups in disease-specific health-related quality of life  or disease severity score  (both low-quality evidence). Systemic antifungals may lead to more hepatic toxicity events (RR 3.35, 95% CI 0.14 to 78.60) but fewer gastrointestinal disturbances (RR 0.37, 95% CI 0.04 to 3.36), compared to placebo, although the evidence was of low quality. This study did not find a difference in CT scan  score between the groups. Generic health-related quality of life  and endoscopic score  were not measured. Other comparisons We found no studies that compared antifungal agents against other treatments for chronic rhinosinusitis. Due to the very low quality of the evidence, it is uncertain whether or not the use of topical or systemic antifungals has an impact on patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment. Studies including specific subgroups (i.e. AFRS) are lacking.

Plain-language summary: We included eight studies (490 adult participants). Seven studies (437 participants) investigated topical antifungals (nasal sprays or irrigations) and one study (53 participants) investigated systemic antifungals (tablets). All studies compared antifungals to placebo or no treatment. Most studies were well conducted and there was a mix of patients with chronic rhinosinusitis both with, and without, nasal polyps. At the end of at least four weeks treatment, none of the studies found that patients using antifungals (topical or systemic) had a better quality of life or less severe symptoms than patients who used placebo or had no treatment. Not many participants in the studies reported having adverse effects. Topical antifungals may lead to more nasal irritation compared with placebo. It is uncertain if patients taking topical antifungals have more headaches or nosebleeds than with placebo. For systemic antifungals, it is uncertain if patients using antifungals have more problems with their liver (hepatic toxicity) than with placebo. Systemic antifungals may lead to fewer patients with gastrointestinal disturbances compared to placebo. We found no studies that compared antifungal treatment with other treatments for chronic rhinosinusitis. We assessed the quality of the evidence as either low (further research is very likely to have an important impact on our confidence in the result) or very low (any estimate of the result is very uncertain), as some of the results are only from one or two studies, which do not have a lot of participants. Moreover, the different studies reported outcomes using different measurement scales making it difficult to draw conclusions. Due to the very low quality of the evidence, it is uncertain whether or not the use of topical or systemic antifungals has an impact on patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment. More trials are needed to assess well-defined patient populations (such as the AFRS subgroup) and to evaluate other antifungals that have not been assessed in randomised controlled trials.