Abstract: We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no intervention Only one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL  using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence). Our second primary outcome, disease severity  , was measured using the Chronic Sinusitis Survey in a second study (134 participants without polyps), which found no important difference (mean difference (MD) 2.84, 95% confidence interval (CI) -5.02 to 10.70; scale 0 to 100). Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group (RR 2.78, 95% CI 1.76 to 4.40; 109 participants). The quality of the evidence was low. Six studies provided data on at least two of the individualsymptoms  used in the EPOS 2012 criteria to define chronic rhinosinusitis (nasal blockage, rhinorrhoea, loss of sense of smell and facial pain/pressure). When all four symptoms in the EPOS criteria were available on a scale of 0 to 3 (higher = more severe symptoms), the average MD in change from baseline was -0.26 (95% CI -0.37 to -0.15; 243 participants; two studies; low quality evidence). Although there were more studies and participants when only nasal blockage and rhinorrhoea were considered (MD -0.31, 95% CI -0.38 to -0.24; 1702 participants; six studies), the MD was almost identical to when loss of sense of smell was also considered (1345 participants, four studies; moderate quality evidence). When considering the results for the individual symptoms, benefit was shown in the intranasal corticosteroids group. The effect size was larger for nasal blockage (MD -0.40, 95% CI -0.52 to -0.29; 1702 participants; six studies) than for rhinorrhoea (MD -0.25, 95% CI -0.33 to -0.17; 1702 participants; six studies) or loss of sense of smell (MD -0.19, 95% CI -0.28 to -0.11; 1345 participants; four studies). There was heterogeneity in the analysis for facial pain/pressure (MD -0.27, 95% CI -0.56 to 0.02; 243 participants; two studies). The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure. There was an increased risk of epistaxis  with intranasal corticosteroids (risk ratio (RR) 2.74, 95% CI 1.88 to 4.00; 2508 participants; 13 studies; high quality evidence). Considering our secondary outcome, general HRQL, one study (134 participants without polyps) measured this using the SF-36 and reported a statistically significant benefit only on the general health subscale. The quality of the evidence was very low. It is unclear whether there is a difference in the risk of local irritation (RR 0.94, 95% CI 0.53 to 1.64; 2124 participants; 11 studies) (low quality evidence). None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis or stunted growth (children). Other comparisons We identified no other studies that compared intranasal corticosteroids plus co-intervention A versus placebo plus co-intervention A. Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life (very low quality evidence). For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).

Plain-language summary: We included 18 randomised controlled trials (RCTs) with a total of 2738 participants in this review. Most studies were relatively small, with as few as 9 or 10 patients per intervention arm. The largest study had 748 patients in total. Most were conducted in tertiary referral centres in northern Europe, the US and Canada. Fourteen studies only included participants with chronic rhinosinusitis with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. The studies looked at a range of types, doses and methods of administration (e.g. spray, drops) of intranasal corticosteroids. One study (20 participants) reported no statistically significant difference in disease-specific health-related quality of life. Another measured general health-related quality of life and reported a statistically significant benefit only on a subscale for general health. Both studies recruited participants with chronic rhinosinusitis without nasal polyps. The quality of the evidence was very low (we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect). Disease severity was measured in one study (chronic rhinosinusitis without nasal polyps, 134 participants), which found no important difference. Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group. The quality of the evidence was low (our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect). When each type of symptom was measured separately (nasal blockage, rhinorrhoea, loss of sense of smell, facial pain/pressure), benefit was shown in the intranasal corticosteroids group. The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure (moderate quality evidence means we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different). There was an increased risk of nosebleeds (epistaxis) with intranasal corticosteroids (high quality evidence). However, it was unclear whether there was a difference in the risk of local (nose or throat) irritation (low quality evidence). None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis (fragile bones) or stunted growth (in children). Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life and the quality of this evidence is very low. For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of nosebleeds is increased (high quality evidence), but this included all levels of severity; for some patients small streaks of blood may not be a major concern. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).