Flunisolide

Abstract: There are significant differences in the pharmacokinetic properties of inhaled corticosteroids currently used in medical practice. All are rapidly cleared from the body but they show varying levels of oral bioavailability and more importantly variation in the rate of absorption after inhalation. Oral bioavailability is lowest for fluticasone propionate, indicating a low potential for unwanted systemic corticosteroid effects. Mathematical modeling has shown pulmonary residence times to be longest for fluticasone propionate and triamcinolone acetonide but shortest for budesonide and flunisolide. These properties appear to relate to pulmonary solubility, which appears to be the rate-limiting step in the absorption process.

Abstract: BACKGROUND: This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. The use of topical (intranasal) corticosteroids has been widely advocated for the treatment of chronic rhinosinusitis given the belief that inflammation is a major component of this condition. OBJECTIVES: To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) against placebo or no treatment in patients with chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation or other systemic adverse events. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: 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 interventionOnly 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 comparisonsWe identified no other studies that compared intranasal corticosteroids plus co-intervention A versus placebo plus co-intervention A. AUTHORS' CONCLUSIONS: 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).

Abstract: BACKGROUND Adenoidal hypertrophy is generally considered a common condition of childhood. When obstructive sleep apnoea or cardio-respiratory syndrome occurs, adenoidectomy is generally indicated. In less severe cases, non-surgical interventions may be considered, however few medical alternatives are currently available. Intranasal steroids may be used to reduce nasal airway obstruction. OBJECTIVES To assess the effectiveness of intranasal corticosteroids for improving nasal airway obstruction in children with moderate to severe adenoidal hypertrophy. SEARCH STRATEGY Our search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), MEDLINE (1951 to 2007) and EMBASE (1974 to 2007). All searches were initially performed in May 2007 and updated in April 2008. SELECTION CRITERIA Randomised controlled trials comparing intranasal corticosteroids with placebo or no intervention or other treatment in children aged 0-12 years with moderate to severe adenoidal hypertrophy. DATA COLLECTION AND ANALYSIS Data from the included trials were extracted and trial quality was assessed by two authors independently. Meta-analysis was not applicable and data were summarised in a narrative format. MAIN RESULTS Five randomised trials, including a total of 349 patients, met the inclusion criteria of the review. All trials except one showed significant efficacy of intranasal corticosteroids in improving nasal obstruction symptoms and in reducing adenoid size. The first eight-week cross-over study showed that treatment with beclomethasone (336 micrograms/day) yielded a greater improvement in mean symptom scores than placebo (-18.5 vs. -8.5, P < 0.05) and a larger reduction in mean adenoid/choana ratio than placebo (right, -14% vs. +0.4%, p=0.002; left, -15% vs. -2.0%, p=0.0006) between week 0 and week 4. The second four-week cross-over study demonstrated that the nasal obstruction index decreased by at least 50% from baseline in 38% of patients treated with beclomethasone (400 micrograms/day) between week 0 and week 2, whereas none of the patients treated with placebo had such improvement (p<0.01). The third randomized, parallel-group trial showed that 77.7% of patients treated with mometasone (100 micrograms/day) for 40 days demonstrated an improvement in nasal obstruction symptoms and a decrease in adenoid size, such that adenoidectomy could be avoided, whereas no significant improvement was observed in the placebo group. The fourth randomized, parallel-group trial showed that eight-weeks of treatment with flunisolide (500 micrograms/day) was associated with a lager reduction in adenoid size than isotonic saline solution (p<0.05). In contrast, one randomised, parallel-group trial did not find significant improvement in nasal obstruction symptoms and adenoid size after eight weeks of treatment with beclomethasone (200 micrograms/day). AUTHORS' CONCLUSIONS Limited evidence suggests that intranasal corticosteroids may significantly improve nasal obstruction symptoms in children with moderate to severe adenoidal hypertrophy, and this improvement may be associated with a reduction of adenoid size. The long-term effect of intranasal corticosteroids in these patients remains to be defined.