Topical and systemic antifungal therapy for chronic rhinosinusitis.

Background: This review adds to a series of reviews looking at primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Antifungals have been suggested as a treatment for chronic rhinosinusitis.

Objectives: To assess the effects of systemic and topical antifungal agents in patients with chronic rhinosinusitis, including those with allergic fungal rhinosinusitis (AFRS) and, if possible, AFRS exclusively.

Search Methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 17 November 2017.

Selection Criteria: Randomised controlled trials (RCTs) with at least a two-week follow-up period comparing topical or systemic antifungals with (a) placebo, (b) no treatment, (c) other pharmacological interventions or (d) a different antifungal agent. We did not include post-surgical antifungal use.

Data Collection And Analysis: We used the standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the significant adverse effects of hepatic toxicity (systemic antifungals). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse effects of gastrointestinal disturbance (systemic antifungals) and epistaxis, headache or local discomfort (topical antifungals). We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.

Main Results: 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 interventionWe 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 treatmentOne 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 comparisonsWe found no studies that compared antifungal agents against other treatments for chronic rhinosinusitis.

Authors' 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. Studies including specific subgroups (i.e. AFRS) are lacking.