Abstract: We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionate We identified two small studies (56 participants with polyps) that evaluated disease severity  and looked at the primary adverse effect: epistaxis  , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The evidence was of very low quality. Fluticasone propionate versus mometasone furoate We identified only one study (100 participants with polyps) that evaluated disease severity  (nasal symptoms scores), which reported no difference (no numerical data available). The evidence was of very low quality. High-dose versus low-dose steroids We included five studies (663 participants with nasal polyps), three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children) and two using fluticasone propionate drops (800 µg versus 400 µg). We found low quality evidence relating to disease severity  and nasal polyps size, with results from the high-dose and low-dose groups being similar. Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear due to the small size of the improvements. The primary adverse effect, epistaxis  , was more common when higher doses were used (risk ratio (RR) 2.06, 95% confidence interval (CI) 1.20 to 3.54, 637 participants, moderate quality evidence). Most of the studies that contributed data to this outcome used a broad definition of epistaxis, which ranged from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. Aqueous nasal spray versus aerosol spray We identified only one poorly reported study (unclear number of participants for comparison of interest, 91 between three treatment arms), in which there were significant baseline differences between the participants in the two groups. We were unable to draw meaningful conclusions from the data. We found insufficient evidence to suggest that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that the effectiveness of a spray differs from an aerosol. We identified no studies that compared drops with spray. It is unclear if higher doses result in better symptom improvements (low quality evidence), but there was moderate quality evidence of an increased risk of epistaxis as an adverse effect of treatment when higher doses were used. This included all levels of severity of epistaxis and it is likely that the proportion of events that required patients to discontinue usage is low due to the low numbers of withdrawals attributed to it. If epistaxis is limited to streaks of blood in the mucus it may be tolerated by the patient and it may be safe to continue treatment. However, it may be a factor that affects compliance. There is insufficient evidence to suggest that the different types of corticosteroid molecule or spray versus aerosol have different effects. Lower doses have similar effectiveness but fewer side effects. Clearly more research in this area is needed, with specific attention given to trial design, disease-specific health-related quality of life outcomes and evaluation of longer-term outcomes and adverse effects.

Plain-language summary: We included nine randomised controlled trials (RCTs) with a total of 910 participants in this review. The studies varied in size: some were small, with as few as 20 patients, while others included over 200 participants. Most studies recruited adult patients, but one study only included children. In the majority of the adult studies, most participants were male (72% to 79%). In all of the studies the participants had chronic rhinosinusitis with nasal polyps. The studies either compared different types of steroids (three studies), high-dose versus low-dose steroids (five studies), twice daily versus once daily steroids, or different delivery methods (aqueous nasal spray versus aerosol - one study). All of the studies had a placebo group. Different steroids: fluticasone propionate versus beclomethasone dipropionate Two small studies (56 participants, unclear risk of bias) evaluated disease severity and looked at the primary adverse effect, epistaxis (nosebleed), but no other outcomes. No difference was found between the two steroids but we assessed the evidence to be of very low quality. Different steroids: fluticasone propionate versus mometasone furoate One study (100 participants, unclear risk of bias) found no difference in disease severity (nasal symptoms scores). We assessed this evidence to be of very low quality. High-dose versus low-dose steroids We found five studies (663 participants, low or unclear risk of bias) that compared high-dose and low-dose steroids, three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children), and two using fluticasone propionate drops (800 µg versus 400 µg). Effectiveness (disease severity and nasal polyps size) was similar between the high-dose and low-dose groups (low quality evidence). Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear because the improvements seen were small. The primary adverse effect, epistaxis, was more common when higher doses were used (moderate quality evidence). Different delivery methods: aqueous nasal spray versus aerosol spray We identified only one poorly reported study with a high risk of bias. It was unclear how many participants there were: 91 were recruited into three arms. There had also been significant differences between the participants in the two groups when they started the study. We were unable to draw any meaningful conclusions from this study. We found no evidence that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that higher doses are better than lower, nor that the effectiveness of a spray differs from an aerosol. We found no studies that compared nasal drops with spray. We did find moderate quality evidence of an increased risk of epistaxis (nosebleed) as an adverse effect of treatment when higher doses were used. More research in this area is clearly needed. In the future studies should be well designed: they should measure chronic rhinosinusitis-specific health-related quality of life and adverse effects as outcomes, and look at what happens to patients taking intranasal steroids in the longer term.