fluticasone and Nasal-Polyps

Nasal sprays with corticosteroids deliver medication to the restricted areas including anterior and inferior parts of the nasal cavity. The fluticasone exhalation delivery system (EDS-FLU) has recently been proved to improve care by increasing superior/posterior intranasal corticosteroid deposition.. This study aims to evaluate the efficacy of EDS-FLU in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).. A systematic literature review using Pubmed, Embase, Cochrane Library, and Web of Science was conducted to identify studies assessing the effect of EDS-FLU on outcomes in patients with CRSwNP.. Of the initial 108 abstracts reviewed, 4 full-text articles were included. The 22-item sinonasal outcome test scores were significantly decreased in patients with CRSwNP after receiving EDS-FLU twice a day (93, 186, or 372 μg) for 16 weeks when compared with exhalation delivery system (EDS)-placebo (all. This is the first systematic review of the clinical outcomes in patients with CRSwNP treated with EDS-FLU. EDS-FLU produced significant improvements regarding the quality of life, smell, and endoscopic assessment of polyp grade.

Topics: Chronic Disease; Exhalation; Fluticasone; Humans; Nasal Polyps; Quality of Life; Rhinitis

The aim of this article is to review the current literature regarding a novel method of topically delivering nasal steroids, namely exhalation delivery system-fluticasone (EDS-FLU), for the treatment of chronic rhinosinusitis (CRS).. Recent Food and Drug Administration approval of EDS-FLU and increasing evidence surrounding its efficacy and safety has led to an additional tool for the treatment of chronic rhinosinusitis. Compared with placebo, EDS-FLU has demonstrated significant improvements in patients' sinonasal symptoms and overall inflammatory control as well as quality of life measures. Additionally, using EDS-FLU can lead to polyp grade improvement and polyp elimination in patients with chronic rhinosinusitis with polyps. Furthermore, compared with controls, patients who received EDS-FLU were less likely to meet predefined surgical criteria at the conclusion of the study.. EDS-FLU has demonstrated significant improvement in managing symptoms and polyps in CRS. Receiving EDS-FLU was associated with a significant reduction in the proportion of patients meeting surgical criteria. Further studies are warranted to evaluate the long-term outcomes of EDS-FLU, especially as compared with steroid sprays and topical steroid irrigations, in management of CRS.

Topics: Administration, Intranasal; Chronic Disease; Drug Delivery Systems; Exhalation; Fluticasone; Glucocorticoids; Humans; Nasal Polyps; Rhinitis; Sinusitis

Advances in understanding the pathogenic mechanisms of both rhinitis and chronic rhinosinusitis have resulted in new treatment options, especially for chronic rhinosinusitis. A review of relevant medical and surgical clinical studies shows that intranasal corticosteroids, antihistamines, and allergen immunotherapy continue to be the best treatments for chronic rhinitis. Dupilumab is the first biologic approved for chronic rhinosinusitis with polyps. Omalizumab, mepolizumab, and benralizumab may have a future role in the treatment of chronic rhinosinusitis. Novel corticosteroid delivery devices such as an exhalation delivery system for fluticasone and bioabsorbable sinus implants provide enhanced and localized distribution of corticosteroids. Surgical management tailored to the underlying disease process improves clinical outcomes in chronic rhinosinusitis with or without nasal polyposis. Advances in the understanding of the heterogeneous nature of rhinitis and rhinosinusitis have resulted in more precise treatments. Improving the understanding of different endotypes should provide better knowledge to determine appropriate current and new therapies to treat these diseases.

Topics: Administration, Intranasal; Chronic Disease; Fluticasone; Humans; Nasal Polyps; Rhinitis; Sinusitis

Intranasal steroids have become part of the mainstay in the long-term management of chronic rhinosinusitis. A long-standing problem remains in efficient and easy-to-use delivery of topical corticosteroids to the nasal mucosa. Currently available means of intranasal steroid delivery include sprays, which are generally limited to treating the anterior nasal cavity, and rinses, which are not FDA-approved for this indication. The exhalation delivery system is a novel method of delivering fluticasone to the deeper areas within the nasal cavities, including the posterior nasal cavity and middle and superior meatuses.. Comprehensive literature review.. Recent large scale studies have suggested its efficacy and safety in the use of patients with both chronic sinusitis with polyposis and without polyps. Specifically, studies have demonstrated decreased Sinonasal Outcome Test scores of 20 points following treatment, as well as improvement of polyp grade by 1 or more point in more than 60% of patients. Furthermore, among patients with nasal polyps, there was approximately 60-70% decreased indication for surgery following EDS-FLU use.. EDS-FLU is an important adjunct therapy for sinonasal inflammatory disease.

Topics: Administration, Intranasal; Chronic Disease; Drug Delivery Systems; Exhalation; Fluticasone; Humans; Nasal Polyps; Rhinitis; Sinusitis; Treatment Outcome

Causality assessment is crucial to post-marketing pharmacovigilance and helps optimize safe and appropriate use of medicines by patients in the real world. Self-reported olfactory and gustatory dysfunction are common in the general population as well as in patients with allergic rhinitis and nasal polyposis. Intranasal corticosteroids, including intranasal fluticasone propionate (INFP), are amongst the most effective drugs indicated in the treatment of allergic rhinitis and nasal polyposis. While intranasal corticosteroids are associated with olfactory and gustatory dysfunction and are currently labeled for these adverse events, causality assessment has not been performed to date. Although there is no single widely accepted method to assess causality in pharmacovigilance, the Bradford Hill criteria offer a robust and comprehensive approach because nine distinct aspects of an observed potential drug-event association are assessed. In this literature-based narrative review, Hill's criteria were applied to determine causal inference between INFP and olfactory and gustatory dysfunction.

Topics: Administration, Intranasal; Adult; Anti-Allergic Agents; Female; Fluticasone; Humans; Nasal Polyps; Olfaction Disorders; Rhinitis, Allergic; Taste Disorders

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, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Topical (intranasal) corticosteroids are used with the aim of reducing inflammation in the sinonasal mucosa in order to improve patient symptoms.. To assess the effects of different types of intranasal steroids in people with chronic rhinosinusitis.. The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.. Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing first-generation intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) with second-generation intranasal corticosteroids (e.g. ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, betamethasone sodium phosphate), or sprays versus drops, or low-dose versus high-dose intranasal corticosteroids.. 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 (nosebleed). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse event of local irritation. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.. 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 steroidsWe 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.

Topics: Administration, Intranasal; Adult; Beclomethasone; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Steroids

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.. To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis.. 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.. 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.. 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.. 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 individual symptoms 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. 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).

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis; Severity of Illness Index; Sinusitis; Steroids

The introduction of nasal glucocorticosteroids, 30 years ago, has been the most important therapeutic progress in rhinitis management since the introduction of the first generation of antihistamines. Our knowledge of the mode of action of glucocorticosteroids in the nose has improved as the airway mucous membrane of the nose is easily accessible for investigation. However, the exact mechanism behind the marked clinical effect remains unclear. Topical glucocorticosteroids are highly effective in diseases characterized by eosinophil-dominated inflammation (allergic rhinitis, nasal polyposis), but not in diseases characterized by neutrophil-dominated inflammation (common cold, infectious rhinosinusitis). Experience for 30 years and a long series of controlled studies have shown that the treatment is highly effective and that the side effects are few and benign. Intranasal glucocorticosteroids can therefore be considered as first-line treatment for allergic and non-allergic, non-infectious rhinitis and nasal polyps.

Topics: Administration, Topical; Androstadienes; Animals; Beclomethasone; Budesonide; Dexamethasone; Eosinophils; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Nasal Mucosa; Nasal Polyps; Pregnadienediols; Randomized Controlled Trials as Topic; Rhinitis; Treatment Outcome; Triamcinolone Acetonide

The intranasal corticosteroid fluticasone propionate is an effective agent for the treatment of rhinitis, demonstrating potent local anti-inflammatory activity and little, if any, systemic activity. Intranasal fluticasone propionate has shown clinical efficacy similar to that of other intranasal corticosteroids, including beclomethasone (administered at up to a 2-fold higher dosage than fluticasone), budesonide, flunisolide and triamcinolone acetonide, and provides greater relief from nasal symptoms (including nasal blockage) than antihistamine agents and intranasal sodium cromoglycate. Its efficacy in the treatment of seasonal allergic rhinitis and perennial allergic and nonallergic rhinitis has been demonstrated in large well-controlled studies in which the drug maintained adequate control of symptoms when administered in a once daily dose of 200 micrograms. In addition, fluticasone propionate has shown similar efficacy to that of beclomethasone in the treatment of nasal polyps; however, its use in the postoperative setting requires further investigation. Intranasal fluticasone propionate is well tolerated in the majority of patients, the incidence of adverse events being similar to that seen with placebo. Pharmacoeconomic analyses indicate that intranasal fluticasone propionate is significantly more cost-effective than the antihistamines terfenadine and loratadine. Overall quality of life was improved to a similar extent by fluticasone propionate and beclomethasone. In conclusion, recent clinical experience has confirmed that intranasal fluticasone propionate is a convenient, effective and well tolerated alternative to other intranasal corticosteroids and antihistamines for the treatment of rhinitis when administered once daily.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Fluticasone; Humans; Nasal Polyps; Quality of Life; Rhinitis

Topics: Adrenal Cortex Hormones; Cataract; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Exhalation; Fluticasone; Humans; Nasal Polyps; Sinusitis

Standard nasal steroid sprays are often first-line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS-FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS-FLU treatment outcomes in patients who have previously failed nasal steroids.. Using pooled data from the NAVIGATE I and II trials, EDS-FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids.. Of 482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for "switchers" receiving EDS-FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS-FLU 372 μg, comparable improvements were observed in congestion (-0.73 vs -0.62), rhinorrhea (-0.71 vs -0.57), facial pain/pressure (-0.48 vs -0.41), and sense of smell (-0.35 vs -0.30) at week 4 and 22-item Sino-Nasal Outcome Test (-21.01 vs -20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS-FLU 186 μg were similar.. EDS-FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.

Topics: Chronic Disease; Exhalation; Fluticasone; Humans; Nasal Polyps; Nasal Sprays; Rhinitis; Steroids

Chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP) seriously impairs health-related quality of life (HRQoL). This analysis describes the impact of the exhalation delivery system with fluticasone (EDS-FLU) on HRQoL, assessed by the 36-item Short-Form Health Survey version 2 (SF-36v2), and on utilities, assessed via the Short-Form 6-Dimension (SF-6D), in patients with CRSwNP.. Post hoc analysis of pooled randomized clinical trial data (NAVIGATE I and II; N = 643) to examine change from baseline in SF-36v2 and SF-6D at end-of-double-blind (EODB: 16 weeks) and end-of-open-label (EOOL: 24 weeks; following 8 weeks of open-label treatment) for EDS-FLU vs placebo (EDS-PBO). Baseline characteristics predictive of change in SF-36 and SF-6D scores were assessed.. Mean baseline SF-36v2 scores were below population norms. At EODB, mean improvement was greater for all SF-36v2 domain and component scores with EDS-FLU (range: 2.9 [physical functioning] to 5.11 [bodily pain {BP}]) vs EDS-PBO (range: 0.81 [mental health] to 2.87 [BP]) (each comparison p < 0.01); physical and mental component score improvements within the EDS-FLU group exceeded the minimal clinically important difference (MCID). Clinically meaningful and statistically significant improvements in SF-6D utility scores were seen in EDS-FLU-treated patients compared to EDS-PBO-treated patients (0.058 vs 0.023, respectively, p < 0.001). At EOOL, SF-36v2 and SF-6D mean scores were at or above population norms, with clinically meaningful and statistically significant improvements from baseline.. In this pooled analysis of 2 large pivotal EDS-FLU trials, health domain and health utilities improvements were significantly greater with EDS-FLU than EDS-PBO and were comparable to population norms.

Topics: Exhalation; Fluticasone; Health Status; Humans; Nasal Polyps; Quality of Life; Surveys and Questionnaires

Chronic rhinosinusitis is common and sometimes complicated by nasal polyps (NPs). Corticosteroid nasal sprays are often unsatisfactory because they are ineffective at delivering medication to high/deep sites of inflammation.. We sought to assess whether an exhalation delivery system with fluticasone (EDS-FLU) capable of high/deep drug deposition improves outcomes.. Patients (n = 323) 18 years and older with moderate-to-severe congestion and NPs were randomized to twice-daily EDS-FLU (93, 186, or 372 μg) or exhalation delivery system (EDS)-placebo for 24 weeks (16 double-blind plus 8 open-label when all received 372 μg). Coprimary end points were change in nasal congestion/obstruction at 4 weeks and summed bilateral polyp grade at 16 weeks. Secondary end points included symptoms, polyp elimination, and functioning.. EDS-FLU was superior on both coprimary end points (P < .001 vs EDS-placebo, all doses). Mean polyp grade improved continuously through week 24 (P < .009, all comparisons), with polyps eliminated on at least 1 side in approximately 25% of patients at week 24 versus 8.7% with EDS-placebo (P ≤ .014, all comparisons). Sino-Nasal Outcomes Test scores also improved significantly versus those in patients receiving EDS-placebo (-21.1 to -21.4 vs -11.7 at week 16, P < .05 all doses). At the end of the double-blind period, EDS-FLU (all doses) significantly improved all 4 defining disease symptoms. In most patients (68%), those receiving EDS-FLU reported "much" or "very much" improvement. The number of patients eligible for surgery decreased by 62%-67%. The safety profile was similar to that reported in prior trials evaluating conventional corticosteroid nasal sprays in comparable populations.. EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.

Topics: Administration, Intranasal; Adult; Chronic Disease; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Rhinitis; Sinusitis

Chronic rhinosinusitis (CRS) can be divided to CRS without nasal polyps (CRSsNP) and eosinophilic and non-eosinophilic CRS with nasal polyps (CRSwNP). There is little evidence on the efficacy of glucocorticoids and macrolides in different phenotypic patients. The aim of this study was to compare the benefit of glucocorticoids and macrolides following endoscopic sinus surgery (ESS) in different phenotypic CRS.. This study was a prospective single-blind comparative effectiveness trial. A total of 187 Chinese patients with CRS were stratified to CRSsNP and eosinophilic and non-eosinophilic CRSwNP group and then randomized to receive fluticasone propionate nasal spray at 200 microgram or clarithromycin tablet at 250 mg once daily for 3 months after ESS. Oral prednisone was given as a rescue therapy after the stop of study medication. Patients were assessed before ESS and 1, 3, 6 and 12 months after dosing. Symptom severity was scored by patients using visual analog scale method and endoscopic findings were scored by the senior physician blinded to treatment according to European Position Paper on Rhinosinusitis and Nasal polyps 2012.. The total and individual symptom scores, and total and individual endoscopic domain scores were reduced significantly after ESS in both medication groups, whereas no significant difference was observed for two medications at most follow-up visits in each subtype of CRS. No difference in the frequency of subjects with rescue therapy or refractory CRS was found between two medication groups either.. We could not show significant difference of effect between fluticasone propionate and clarithromycin in the post-operative treatment for CRSsNP and eosinophilic and non-eosinophilic CRSwNP patients.

Topics: Anti-Bacterial Agents; Chronic Disease; Clarithromycin; Fluticasone; Humans; Nasal Polyps; Prospective Studies; Rhinitis; Single-Blind Method; Sinusitis

Chronic rhinosinusitis is a common, high-morbidity chronic inflammatory disease, and patients often experience suboptimal outcomes with current medical treatment. The exhalation delivery system with fluticasone (EDS-FLU) may improve care by increasing superior/posterior intranasal corticosteroid deposition.. To evaluate the efficacy and safety of EDS-FLU versus EDS-placebo in patients with nasal polyps (NP). Coprimary end points were change in nasal congestion and polyp grade. Key secondary end points were Sino-Nasal Outcome Test-22 (SNOT-22) and Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R). Other prespecified end points included all 4 cardinal symptoms of NP, 36-Item Short Form Health Survey (SF-36), Patient Global Impression of Change (PGIC), Rhinosinusitis Disability Index (RSDI), and key indicators for surgical intervention.. Randomized, double-blind, EDS-placebo-controlled, multicenter study.. Three hundred twenty-three subjects with NP and moderate-severe congestion/obstruction, most with history of corticosteroid use (94.4%) and/or prior surgery (60.4%), were randomized to EDS-FLU 93 µg, 186 µg, or 372 µg or EDS-placebo twice daily (BID) for 24 weeks (16 double-blind + 8 single-arm extension with EDS-FLU 372 µg BID).. All EDS-FLU doses produced significant improvement in both coprimary end points ( P < .05) and in SNOT-22 total score ( P ≤ .005). EDS-FLU significantly improved all 4 cardinal symptoms of NP ( P < .05), including congestion/obstruction, facial pain/pressure, rhinorrhea/post-nasal drip, and hyposmia/anosmia. Approximately 80% of subjects reported improvement with EDS-FLU, with 65% reporting "much" or "very much" improvement by week 16. Adverse events were generally local in nature and similar to other intranasal steroids studied for similar durations in similar populations, with the most common being epistaxis.. In patients with chronic rhinosinusitis with NP (CRSwNP) who were symptomatic despite high rates of prior intranasal steroid use and/or surgery, EDS-FLU produced statistically significant and clinically meaningful improvements compared to EDS-placebo in multiple subjective and objective outcomes (symptoms, SNOT-22, RSDI, SF-36, PGIC, and NP grade), including all 4 cardinal symptoms of CRSwNP.

Topics: Adult; Chronic Disease; Double-Blind Method; Drug Delivery Systems; Exhalation; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Neoplasm Grading; Placebo Effect; Rhinitis; Sinusitis; Treatment Outcome

Topics: Adult; Aged; Chronic Disease; Dexamethasone; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Nasal Sprays; Natural Orifice Endoscopic Surgery; Postoperative Care; Rhinitis; Secondary Prevention; Sinusitis; Treatment Outcome; Young Adult

Topics: Administration, Topical; Cefixime; Drug Therapy, Combination; Fluticasone; Follow-Up Studies; Furosemide; Humans; Nasal Polyps; Paranasal Sinus Diseases; Postoperative Complications; Research Design; Secondary Prevention

We investigated the effect of topical steroids on clinical outcomes and related immune response of chronic rhinosinusitis with nasal polyp (CRSwNP) patients and in eradicating some polyps. We want to explore a new potential mechanism linked to Th-17 cells.. Prospective, double-blind, placebo-controlled studies with 24 allergic and nonallergic patients were randomized to either placebo or fluticasone furoate for 12 weeks. Assessment of clinical response, endoscopic score with biopsies of the inferior turbinate, and polyps before and after treatment were performed. Biopsies were stained for T-cells, eosinophils, neutrophils, and IL-17A/F.. Steroid treatment improved the mean symptoms scores from 7.12 to 4.02 (P < .01) and the polyp score from 5.13 to 3.31 (P < .05), but the comparison with placebo was not statistically significant in nonallergics due to insufficient study power. Steroid treatment decreased eosinophil counts on allergics but not neutrophils or T-cells. The IL-17A/F expression was higher in nonallergics with high neutrophil counts and was inclined by steroids. Compared to baselines, IL-17 cells were significantly less in allergic individuals and were not observed in allergics and with high neutrophil counts.. Topical steroids were more effective on certain nasal polyp phenotypes. Identification of polyp phenotype might be essential to ensure a better therapeutic response to intranasal corticosteroids.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Chronic Disease; Double-Blind Method; Female; Fluticasone; Humans; Immunoenzyme Techniques; Interleukin-17; Male; Middle Aged; Nasal Polyps; Prospective Studies; Rhinitis; Sinusitis

Nasal steroids are a critical part of the management of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic sinus surgery (ESS). Increasingly, practitioners are using budesonide respules delivered to the sinonasal cavities, which is an off-label use, in lieu of traditional nasal steroids. There has been little research comparing budesonide with traditional nasal steroids and the most effective delivery method of budesonide.. A randomized controlled trial was performed on patients after ESS for CRSwNP in a tertiary care center. Patients were randomized into 1 of 3 groups: group A received fluticasone nasal spray twice daily; group B received budesonide respules via a mucosal atomization device (MAD) twice daily; and group C received budesonide respules instilled via the vertex-to-floor (VF) position twice daily. Primary endpoints were 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy scores at 6 months.. Thirty-two patients were enrolled in the study, 23 of whom completed the 6-month trial. There were no significant differences among groups A, B, and C with respect to age, gender, asthma, aspirin sensitivity, or previous ESS. Group B had a statistically significant greater reduction in SNOT-22 and Lund-Kennedy scores at the primary endpoint of 6 months compared to groups A and C. Group C had the next greatest reduction, which was statistically significant, followed by group A.. Patients treated with budesonide after ESS for CRSwNP had greater improvement in SNOT-22 and Lund-Kennedy scores compared to fluticasone at 6 months. The data supports the use of budesonide respules, particularly with a MAD, over fluticasone for CRSwNP patients after ESS.

Topics: Adult; Budesonide; Chronic Disease; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Nasal Sprays; Nebulizers and Vaporizers; Paranasal Sinuses; Rhinitis; Rhinoplasty; Sinusitis; Treatment Outcome

Clara cell protein 16 (CC16) is an anti-inflammatory protein mainly expressed in the epithelial cells in the upper and lower airways. Eosinophil cationic protein (ECP) is an important marker of eosinophil activity in chronic inflammatory sinonasal diseases. The aim of this study was to evaluate mucosal production of CC16 and ECP in patients with perennial allergic rhinitis (PAR), nonallergic and allergic patients with chronic rhinosinusitis with nasal polyposis (CRSwNP), before and after nasal corticosteroid administration.. Twenty patients with PAR, 20 nonallergic CRSwNP patients, 20 allergic CRSwNP patients, and 20 healthy controls were included. Mucosal cytology samples were taken from all participants for quantification of eosinophils. CC16 and ECP levels were measured in the nasal secretion samples. The patients with chronic sinonasal inflammation were treated with fluticasone nasal spray for 14 days. Nasal symptoms assessment, cytological examination, and CC16 and ECP nasal fluid measurements were performed before and after the corticosteroid treatment.. Mean CC16 concentrations in nasal secretions were significantly lower in patients with PAR (p < 0.05) and allergic CRSwNP patients (p < 0.01) compared to controls. Mean ECP levels were significantly higher in patients with PAR, nonallergic CRSwNP patients, and allergic CRSwNP patients compared to the control group (p < 0.001, p < 0.01, p < 0.001, respectively). After nasal corticosteroid therapy, we found a highly significant increase of CC16 (p < 0.001) and reduction of ECP (p < 0.001) in nasal secretions in all 3 groups of patients.. CC16 and ECP measured in nasal secretions could be reliable markers for assessment of the recovery function of sinonasal mucosa during corticosteroid treatment.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Chronic Disease; Eosinophil Cationic Protein; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Rhinitis; Sinusitis; Uteroglobin

Chronic rhinosinusitis is a common inflammatory condition in western countries. Nasal polyposis has different symptoms such as nasal obstruction, anterior or posterior nasal drip, reduced sense of smell, and facial pain. Medical and endoscopic treatments are the two main treatments for nasal polyposis. Our aim was to compare the efficacy of different methods on olfactory function. This is a non-randomized clinical trial study that was done on 60 patients who were divided into two groups (medical and surgical). Patients were matched based on age, history of smoking, and the severity of obstruction. The radiologist score of Lund-Mackay staging system was used to match patients in two arms of the trial based on the severity of nasal obstruction. Patients in surgery groups underwent functional endoscopic sinus surgery under general anesthesia and then received Fluticasone propionate nasal spray for 8 weeks (400 mcg bd). Patients in the medical group were only prescribed with Fluticasone propionate with the same duration and same dose as mentioned. As a result of treatment protocol, both medical and surgical group experienced improvement in olfactory function but statistical analyses revealed that surgery resulted in better resolution of symptoms. Our observation revealed that combined treatment had a better effect than medical treatment in restoring olfaction in patients with nasal polyposis.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Chronic Disease; Combined Modality Therapy; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Nasal Sprays; Olfaction Disorders; Paranasal Sinuses; Rhinitis; Sinusitis; Treatment Outcome; Young Adult

A combined therapy of fluticasone propionate nasal drops (FPND) and functional endoscopic sinus surgery (FESS) can improve quality of life (QoL). When compared with prior data, the results imply that a generic measure of psychological aspects of QoL may be better than measures of respiratory symptoms and clinical parameters to capture a patient's perception of the disease and its treatment.. To better understand effects of FPND and FESS on generic QoL.. Sixty nasal polyposis patients with concomitant asthma completed participation in a randomized, double-blind, placebo-controlled, 14-week study in which they responded to the General Well-Being Schedule (GWBS).. GWBS scores (i) increased significantly after administration of FPND, independent of FESS (from lower than normal to normal), (ii) increased after FESS independent of FPND (from lower than normal to normal), and (iii) increased additively after FPND and FESS.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Prospective Studies; Quality of Life; Sinusitis

Topics: Administration, Oral; Adult; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Glucocorticoids; Humans; Male; Nasal Polyps; Prednisolone; Time Factors

Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps.. The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment.. Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).. Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Quinolines; Rhinitis, Allergic, Perennial; Sinusitis; Sulfides; Tomography, X-Ray Computed; Treatment Outcome

The aim was to investigate the health impact of nasal polyposis with asthma and to study effects of endoscopic sinus surgery (ESS), and addition of fluticasone propionate nasal drops (FPND), on health related quality of life (HRQoL).. Prospective study of 68 patients with nasal polyposis and asthma. Effects were measured with Study 36-Item Short Form (SF-36). A randomized, double-blind, placebo-controlled 14-weeks phase measuring additive effects of FPND 400 µg twice daily (b.i.d.) was included.. HRQoL was significantly decreased in both Physical Component Summary, PCS, (45 vs 48, p=0.049) and Mental Component Summary, MCS, (43 vs 51, p<0.001) vs reference population. ESS significantly improved PCS, (p=0.027) and MCS (p=0.021) after five weeks. We found significant additional benefit of FPND on three domains (RP, p=0.002; VT, p=0.007; SF, p=0.002). The increase in HRQoL with FPND reached reference population levels in all domains, as well as in both PCS (50, p=0.003) and MCS (52, p=0.002), five weeks after ESS.. FPND 400 µg b.i.d. can be added to ESS in order to improve, and to reach population levels of, HRQoL already five weeks post-ESS. Physicians should evaluate HRQoL and consider ESS with nasal steroids early in their treatment of these patients.

Topics: Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Comorbidity; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Quality of Life

Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied.. The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis.. This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND.. Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables.. Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Olfaction Disorders; Paranasal Sinuses; Peak Expiratory Flow Rate; Prospective Studies; Smell

Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course.. The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 microg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 microg bd and FPANS 200 microg once a day (od) in maintenance and long-term treatment.. Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 microg bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 microg bd during acute period and FPANS 200 microg od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 microg bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade.. After acute period and maintenance periods, FPANS 200 microg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 microg od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events.. The study demonstrated the efficacy of FPANS 200 microg bd in acute treatment and FPANS 200 microg od as a sufficient dose to maintain a long-term efficacy in the treatment for NP.

Topics: Administration, Intranasal; Androstadienes; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps

To assess the efficacy and safety of fluticasone propionate administered using OptiNose's novel delivery device (Opt-FP) in subjects with bilateral mild-to-moderate nasal polyposis.. A prospective, multicentre, randomized, double-blind, placebo-controlled, parallel group study was conducted in adult subjects (n = 109) with mild-to-moderate bilateral nasal polyposis. Subjects received Opt-FP 400 microg or placebo twice daily for 12 weeks. Endpoints included endoscopic assessment of polyp size using Lildholdt's Scale, peak nasal inspiratory flow (PNIF), symptom scores and use of rescue medication.. The proportion of subjects with improvement in summed polyp score >or= 1 (Lildholdt\\'s Scale) was significantly higher with Opt-FP compared with placebo at 4, 8 and 12 weeks (22% vs 7%, p = 0.011, 43% vs 7%, p < 0.001, 57% vs 9%, p < 0.001). After 12 weeks the summed polyp score was reduced by 35% (-0.98 vs +0.23, p < 0.001). PNIF increased progressively during Opt-FP treatment (p < 0.05). Combined symptom score, nasal blockage, discomfort, rhinitis symptoms and sense of smell were all significantly improved. Rescue medication use was lower (3.1% vs 22.4%, p < 0.001). Opt-FP was well tolerated.. Fluticasone propionate (400 microg b.i.d.) administered using OptiNose's breath actuated bi-directional delivery device was an effective and well tolerated treatment for mild-to- moderate bilateral nasal polyposis.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Equipment Design; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Nebulizers and Vaporizers; Prospective Studies; Treatment Outcome; Young Adult

We assessed the efficacy of different forms of fluticasone propionate in the treatment of bilateral nasal polyposis in adult patients.. This double-blind, randomized, parallel group study included 34 patients, aged 16 years or over, with a diagnosis of bilateral nasal polyposis. The patients were randomized to three groups to receive fluticasone propionate in the form of aqueous nasal spray 100 microg twice daily, or nasal drop preparation 400 microg once or twice daily for 12 weeks. Once every four weeks, nasal volumes were measured by acoustic rhinometry and polyp size was assessed by a 4-mm rigid endoscope. Clinical symptom scores were assessed once a week.. The mean nasal polyp scores decreased significantly in all the groups (p<0.005). Total nasal volume did not improve significantly with the nasal spray. Although single daily nasal drop application increased total nasal volume significantly only at the end of treatment (p<0.05), increases with twice daily application were significant at 4, 8, and 12 weeks, compared to the baseline values and corresponding values of the other two groups (p<0.005). Nasal blockage and rhinitis symptom scores improved in all the groups (p<0.05), but the difference from the baseline was highest with twice daily nasal drop application. Smelling showed a significant improvement only with twice daily nasal drop application (p<0.05). In none of the groups did nasal discomfort scores differ significantly from the baseline at the end of treatment.. Nasal drop preparation of fluticasone propionate given twice daily showed the highest efficacy in increasing total nasal volume, decreasing nasal polyp size, and improving smelling and nasal blockage.

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Nasal Polyps; Nose; Prospective Studies; Rhinitis; Rhinometry, Acoustic; Smell; Treatment Outcome; Young Adult

The objective of this study was to determine the influence of individual anatomical differences on intranasal drug deposition. The data of a comparison of seven different administration techniques in ten healthy volunteers was used in this single-blind crossover pilot study. After intranasal administration of a dyed test formulation, endoscopic video imaging was done on seven non-sequential days. The deposition pattern per individual around the head of the middle turbinate was analyzed for each technique and correlated with the individual anatomy. Decreased deposition of dyed test formulation in the target area around the head of the middle turbinate was observed in the presence of minor septal deviations, narrow nasal valve areas, or inferior turbinate hypertrophy; a lateral head position helps to bypass a minor septal deviation. Although results are preliminary, we conclude that anatomy and head position are important factors in the deposition of topical nasal drugs and may be the key to improving individual local nasal (steroid) treatment.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Cross-Over Studies; Endoscopy; Female; Fluticasone; Humans; Male; Nasal Polyps; Nose; Pilot Projects; Posture; Rhinitis; Single-Blind Method; Sinusitis; Treatment Outcome; Turbinates; Videotape Recording

Steroid treatment is the mainstay of therapy for nasal polyps and rhinosinusitis. Oral steroids have considerable systemic side effects, and nasal sprays do not sufficiently reach the middle meatus, where polyps originate. Nasal drops might be a more useful formula to deliver steroids into the middle meatus.. We sought to investigate whether treatment with fluticasone propionate nasal drops (FPNDs) can reduce the need for surgery, as measured by signs and symptoms of nasal polyposis and chronic rhinosinusitis, in patients who are on the waiting list for functional endoscopic sinus surgery (FESS).. Fifty-four patients (28 male) with severe nasal polyposis, chronic rhinosinusitis, or both indicated for FESS were included in a 12-week, double-blind, placebo-controlled study. Use of intranasal steroid spray was stopped at least 4 weeks before randomization. Signs and symptoms were recorded before, during, and at the end of the study period. At the end of the study, a computed tomographic scan was performed, and the need for operation was reassessed by using a standardized scoring method.. FESS was no longer required in 13 of 27 patients treated with FPNDs versus 6 of 27 in the placebo group (P < .05). Six patients from the placebo group dropped out versus 1 from the FPND group. Symptoms of nasal obstruction, rhinorrhea, postnasal drip, and loss of smell were reduced in the FPND group (P < .05). Peak nasal inspiratory flow scores increased significantly (P < .01). Polyp volume decreased in the FPND group (P < .05), and computed tomographic scores improved in both groups (P < .05).. Treatment with FPNDs in patients indicated for FESS can reduce the need for surgery.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Chronic Disease; Double-Blind Method; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Rhinitis; Sinusitis; Solutions

Topical nasal steroids such as beclomethasone dipropionate and fluticasone propionate have been widely used in the treatment of rhinitis and polyposis. An increase in infection has occurred with the use of fluticasone propionate after endoscopic polypectomy.. The purpose of this study was to determine the prevalence of nasal and paranasal infections with the use of topic nasal steroids after endoscopic polypectomy and to compare the recurrence rates of the polyposis.. We conducted a prospective, comparative, open, experimental, longitudinal study at an academic tertiary referral medical center.. One hundred sixty-two patients in whom endoscopic polypectomy had been indicated were randomly divided into 3 groups of 54 patients each. The patients from the first group were treated with saline lavage only. Patients from the second group also received fluticasone propionate 400 microg/day in nasal spray after lavage. Patients from the third group received beclomethasone dipropionate 600 microg/day after lavage. The prevalence of infections and recurrence of polyposis was compared in the 3 groups.. Three patients, 2 in the placebo group and 1 in the beclomethasone group, developed infections during the first 3 months after surgical procedure. The recurrence of polyps in the group without steroids was 44%. In contrast, 15% from the patients treated with fluticasone showed recurrence of polyposis; furthermore, 26% of the patients treated with beclomethasone showed recurrence of polypsosis, with a minimum follow-up of 12 months.. The use of nasal steroids does not seem to increase the prevalence of infections after endoscopic polypectomy.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Otorhinolaryngologic Surgical Procedures; Prevalence; Prospective Studies; Recurrence; Sinusitis

Prostaglandins and leukotrienes are implicated in conditions of both the upper and lower airways. In the former they are deranged in nasal polyposis, intrinsic rhinitis and allergic rhinitis while in the latter they are involved in the pathogenesis of asthma. The aim of the present study was to measure mucosal eicosanoid levels in the three types of rhinitis and compare with controls. In addition, the effect of topical steroids on eicosanoid levels in rhinitis was examined. The levels of prostaglandins E(2) (PGE(2)) and D(2) (PGD(2)) and of leukotrienes E(4) (LTE(4)) and B(4) (LTB(4)) were measured in nasal biopsies from the inferior turbinates of patients suffering from perennial rhinitis and a control group. Rhinitis patients were classified into three categories: perennial allergic rhinitis (PAR), non-allergic rhinitis with eosinophilia (NARES) and noneosinophilic non-allergic rhinitis (NENAR) on the basis of symptoms, secretion eosinophilia, nasal resistance and allergy testing. Patients with rhinitis were randomized into two groups. One received fluticasone propionate nasal spray (FPANS) and the other a placebo (PNS) over a period of six weeks prior to the biopsies. One hundred and one patients with PAR, NARES or NENAR were recruited sequentially and the control group consisted of 21 patients with no evidence of rhinitis but with nasal obstruction due to septal deviation. Untreated rhinitics had significantly lower levels of PGE(2), PGD(2) and LTE(4) than non-rhinitic controls. Six-weeks' treatment with FPANS significantly increased the levels of those eicosanoids in patients with PAR and NARES but they were still significantly below normal. Levels of LTB(4) in all three rhinitis groups were not significantly different from controls and treatment with topical steroids had no effect. Their findings are contrary to current thinking that increased levels of eicosanoids, in particular cysteinyl-leukotrienes, play an important role in the pathogenesis of chronic, non-infective upper airway inflammation.

Topics: Airway Resistance; Androstadienes; Anti-Inflammatory Agents; Chronic Disease; Dinoprostone; Double-Blind Method; Eosinophils; Fluticasone; Humans; Leukocyte Count; Leukotriene B4; Leukotriene E4; Leukotrienes; Nasal Mucosa; Nasal Polyps; Prostaglandin D2; Prostaglandins; Rhinitis; Rhinitis, Allergic, Perennial

Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo-controlled trials.. This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS.. The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS.. A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery.. This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Chronic Disease; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Paranasal Sinuses; Secondary Prevention; Sinusitis; Treatment Outcome

To observe the effects of intranasal Fluticasone propionate on the expression of Aquaporin-5 in nasal polyps and explore the role of AQP-5 in the formation of nasal polyps.. Twenty cases of nasal polyps were selected. Fluticasone propionate were intranasally used in 10 cases of nasal polyps for 7-10 days before operation. The others, treated with nothing, were used as control. Twenty samples nasal polyps were obtained and studied with immunochemistric technique.. The expression of AQP-5 positive cells in the blood vessel endothelium was statistically significantly redueced in the Fluticasone propionate-using group compared with the control group (P < 0.05). The difference of AQP-5 positive cells in mucosal epithelial and glandular epithelium was not statistically significant between the Fluticasone propionate-using group and the control group.. (1) AQP-5 might be a vital factor for the formation edema of nasal polyps. (2) The effects of Fluticasone propionate on nasal polyps may be related to changing the expression of AQP-5 to a degree. (3) The full exploration of regulation and control of Aquaporions can contribute to evaluate the pathogenesis of nasal polyps.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Aquaporin 5; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps

The objectives of the management of nasal polyposis are to eliminate or reduce the size of polyps, reestablish nasal breathing, reduce symptoms of rhinitis, restore the sense of smell, and prevent the recurrence of nasal polyps. Local or systemic steroids have been used in the treatment of nasal polyps, but efficacy of combined (local and systemic) steroids in nasal polyposis has been little investigated. The aim of this study was to evaluate the influence of combined steroid therapy on the symptoms and extent of the disease in patients with nasal polyposis.. Seventeen patients with nasal polyps were treated with combined steroids. Before and after the therapy, polyp size, nasal symptoms, sense of smell, and headache or facial pain were assessed by an established scoring system.. After the therapy, symptom scores of all the patients improved. Of the patients, 12% showed a polyp-free nasal cavity, 76% a clear involution of polyps, and 12% no response to the therapy. There were statistically significant differences (P<0.001) for symptom scores and polyp size. Medical ablation of polyps using steroids was not achieved in 88% patients.. Steroids can reduce polyp sizes and improve the symptoms, but are inadequate to eradicate the polyps. Surgery still plays a major part in the treatment of the nasal polyposis, but steroids can delay the necessity for surgical intervention.

Topics: Administration, Intranasal; Administration, Oral; Adult; Aged; Androstadienes; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged; Nasal Polyps; Prospective Studies; Severity of Illness Index; Smell; Sneezing; Tomography, X-Ray Computed; Treatment Outcome

Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features.. Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression.. Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means.. Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance.. NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.

Topics: Adult; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Basement Membrane; Collagen; Connective Tissue; Double-Blind Method; Female; Fluticasone; Humans; In Situ Hybridization; Interleukin-11; Interleukin-17; Male; Middle Aged; Nasal Polyps

Treatment of nasal polyposis with topical betamethasone is associated with suppression of the hypothalamo-pituitary-adrenal (HPA) axis and, potentially, has adverse effects on bone turnover. Fluticasone propionate is a potent corticosteroid with negligible absorption across the nasal mucosa and extensive first-pass hepatic metabolism. We performed a randomized double-blind study, in patients with nasal polyposis, comparing the effects of 8 weeks' treatment with betamethasone drops or fluticasone nasules on the HPA axis using the 1 micro g tetracosactide test, and on bone turnover using two serum markers. Nine patients were allocated to each treatment. Betamethasone resulted in significant suppression in the tetracosactide test (P = 0.006), but fluticasone did not (P = 0.113). There were no differences in bone turnover or treatment efficacy between treatments. Treatment of nasal polyposis with topical betamethasone drops, but not with fluticasone nasules, suppresses the HPA axis and, given comparable efficacy, fluticasone administered via nasule should be the preferred agent.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Betamethasone; Bone and Bones; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nasal Polyps; Pituitary-Adrenal System

Topical corticosteroids are the accepted medical adjunct to surgery in patients suffering from nasal polyposis. Fluticasone propionate (FP) is a potent, topically active corticosteroid which has been formulated as nasal drops specifically for the treatment of polyposis.. To evaluate dose-related efficacy and tolerability of FP nasal drops (FPND) in the treatment of mild to moderate bilateral polyposis; in a double-blind, placebo-controlled, multicentre international study.. Adult patients (n = 142) with bilateral nasal polyps were randomized to receive either FPND 400 microg once daily (o.d.), FPND 400 microg twice daily (b.i.d.) or placebo for 12 weeks. The majority then entered a further 12 week open period during which all patients received FPND 400 microg o.d. The primary efficacy endpoint was the physicians' visual assessment of polyp size. Secondary clinical endpoints were nasal blockage and overall rhinitis (0-3 scores), peak nasal inspiratory flow (PNIF), olfactory function tests, and requirement for polypectomy. The patients also kept twice daily records of symptom scores, peak nasal inspiratory flow (PNIF) and use of rescue medication.. At the end of the 12 week randomized treatment period, polyp size was reduced significantly by FPND 400 microg b.i.d. as compared with placebo (P = 0.006). Clinical assessments of nasal blockage and overall rhinitis showed significant improvements at several stages of treatment with both doses of FPND. Clinic PNIF was also improved significantly by both doses of FPND in comparison with placebo, and FPND 400 microg b.i.d. was significantly more effective than 400 microg o.d. (P = 0.045). Patient diary card scores supported the clinical assessments. Two patients on placebo required polypectomy and all treatments were well tolerated with a similar incidence of adverse events.. FPND 400 microg once or twice daily is an effective and well-tolerated treatment for bilateral nasal polyposis.

Topics: Administration, Intranasal; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Placebos

Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti-inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis.. To assess efficacy and tolerability of FPND in the treatment of bilateral nasal polyposis in adults.. This multicentre, randomized, parallel-group study compared FPND 400 microgram once daily (o.d.) with placebo for 12 weeks in adult patients with mild to moderate bilateral polyposis. The primary efficacy endpoint was visual assessment of polyp size by the physician at monthly clinic visits. Nasal blockage, rhinitis, peak nasal inspiratory flow (PNIF), olfactory function and requirement for polypectomy were also assessed at visits. The patients kept diary card records of symptoms, PNIF, and use of rescue antihistamine. Additional safety data were provided by a 12-week open extension, when all patients received FPND 400 microgram o.d.. After 12 weeks double-blind treatment with FPND (n = 52) or placebo (n = 52), polyp size was reduced in 27% and 16% of patients, respectively; clinical reduction of nasal blockage significantly favoured FPND over placebo (55% vs 22%; P = 0.002), and clinic PNIF had increased significantly with FPND (by 52 L/min vs -3 L/min for placebo; P < 0.001). Diary card measurements showed significant benefits of FPND vs placebo for daily PNIF, nasal blockage, rhinitis and use of loratadine rescue medication. Both treatments were well tolerated and no serious adverse events occurred during randomized treatment. Epistaxis was more frequent with FPND than placebo but was generally mild and did not result in withdrawals. Mean serum cortisol levels did not change significantly with either treatment.. This study showed FPND 400 microgram o.d. to be an effective and well tolerated treatment for bilateral nasal polyposis in adults.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps

Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone.. We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1beta).. Twenty subjects (9 women and 11 men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of 1 month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 microg or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test.. Fluticasone treatment significantly reduced NP eosinophilia (P =.02) and CD4(+) T lymphocytes (P =.02). Eosinophils expressing the marker EG2 were more significantly reduced (P =.007). Fluticasone also reduced the expression of P-selectin (P =.005) and the number of IL-4 and IL-13 mRNA+ cells (P =.02 and.05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1beta mRNA+ cells in the polyps.. We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Blood Proteins; Double-Blind Method; Endothelium, Vascular; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Gene Expression; Humans; Inflammation Mediators; Interleukin-13; Interleukin-3; Interleukin-4; Male; Middle Aged; Myelin Basic Protein; Nasal Polyps; P-Selectin; Peak Expiratory Flow Rate; Placebos; Ribonucleases; RNA, Messenger; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Corticosteroids are an effective treatment for nasal polyposis. The exact mechanism of action is not certain. Recent research demonstrates that apoptosis (programmed cell death) in inflammatory cells is an important factor in the resolution of inflammation, and apoptosis is induced in eosinophils in cell culture with steroids. We hypothesized that inflammatory cell apoptosis is a key feature of regression of nasal polyps on exposure to steroids and examined this hypothesis in vivo and in vitro.. A double-blind, placebo-controlled pilot study of fluticasone propionate aqueous nasal spray (FPANS) in nasal polyposis in humans in vivo was undertaken, and the effect of treatment on indices of cell death and proliferation measured. In addition, explants of nasal polyp tissue were maintained in vitro in short-term tissue culture with dexamethasone at increasing doses (0.1-50 micromol) over varying time intervals and then analyzed for similar indices of proliferation and cell death.. Apart from a marginal increase in apoptotic:mitotic ratio in epithelium, little difference between the effect of FPANS and placebo was demonstrated in vivo. However, in vitro, apoptotic index was significantly increased in the stromal layers in relation to time of incubation (P = .0169), and a significant dose-response relationship was demonstrated at 24 hours between stromal cell apoptosis and dexamethasone concentration (P = .001). Eosinophil apoptosis was confirmed by in situ end labeling and transmission electron microscopy. No steroid or time effect on epithelial cells was demonstrated in vitro.. Corticosteroids induce apoptosis in inflammatory cells in human nasal polyps in vitro. This is not reflected by a similar response to FPANS at 14 days in vivo, but may still play a part in regression of polyps with other forms of administration or at other time points.

Topics: Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Apoptosis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; In Vitro Techniques; Male; Middle Aged; Nasal Polyps

The efficacy and safety of fluticasone propionate (FP) nasal drops were investigated in two multicentre, randomized, placebo-controlled trials. Patients received FP 400 microg once or twice daily for 12 weeks and then FP 400 microg once daily for a further 12 weeks. FP 400 microg significantly reduced polyp size and improved peak nasal inspiratory flow, rhinitis symptoms and sense of smell when administered twice daily. Significant reductions in polyp size were not achieved with once daily administration, but clinical benefits were observed for peak nasal inspiratory flow. Both dosing regimens were well tolerated, with an overall incidence of adverse events which was similar to placebo.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Fluticasone; Follow-Up Studies; Humans; Nasal Polyps; Time Factors

To investigate the effect of intranasal corticosteroids in the treatment of polyps in patients with severe polyposis listed for surgical treatment and to determine the treatment effect on the progression of the disease.. A double-blind, randomized, parallel-group, placebo-controlled, 12-week study at a single center.. A tertiary referral center in London, England.. Thirty-four patients with severe polyposis listed for endoscopic surgical treatment.. By random allocation, fluticasone propionate aqueous nasal spray (FPANS), 200 microg twice a day; beclomethasone dipropionate aqueous nasal spray, 200 microg twice a day; or placebo nasal spray twice a day was administered. Patients received 2 actuations to each nostril in the morning and in the evening.. Efficacy end points were the need for polypectomy at the end of treatment, the results of acoustic rhinometry, the polyp score, the peak nasal inspiratory flow rate, and an assessment of symptoms.. The polyp score was significantly decreased in the FPANS-treated group (P < or = .01). The nasal cavity volume was significantly increased in both the FPANS-treated group and the group receiving beclomethasone compared with placebo (P < or = .01) at the end of treatment. The percentage change in the mean morning peak nasal inspiratory flow rate was greater in the FPANS-treated group, with a significant effect observed at week 2 (P = .01). Nasal blockage was significantly decreased in both active groups compared with the group receiving placebo. No significant difference was observed between the treatment groups in the number of patients requiring polypectomy.. Fluticasone and beclomethasone aqueous nasal sprays are effective in treating the symptoms of severe nasal polyps. There was some evidence that the group treated with FPANS responded more quickly to intervention and that the magnitude of the response was greater than in the group receiving beclomethasone.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Disease Progression; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Pilot Projects; Treatment Outcome

Topical glucocorticoids are the medical treatment of choice in a majority of patients suffering from nasal polyposis. Fluticasone propionate is a fluorinated steroid reported to be highly effective when used topically in the nose for seasonal and perennial allergic and nonallergic rhinitis.. To evaluate the efficacy and tolerability of intranasal fluticasone propionate in the treatment of long-standing polyposis.. Fifty-five patients with long-standing nasal polyposis were treated over a 26-week period with fluticasone propionate aqueous nasal spray 200 micrograms bid, beclomethasone dipropionate aqueous nasal spray 200 micrograms bid or placebo, administered intranasally in an aqueous spray in a double-blind, placebo-controlled parallel-group design at a single center. The primary efficacy endpoint was the physicians' assessment of symptoms and polyp score. Peak nasal inspiratory flow was performed twice daily and on every visit to evaluate the effect of the corticosteroids on nasal air flow.. A significant difference in the primary efficacy endpoint between fluticasone propionate aqueous nasal spray and beclomethasone dipropionate aqueous nasal spray compared with placebo was seen after 14 weeks of treatment. This was further verified by the peak nasal inspiratory flow results. There was some evidence of earlier onset in the fluticasone propionate aqueous nasal spray group compared with the beclomethasone dipropionate aqueous nasal spray group after 4 weeks in terms of the primary efficacy endpoint. From the daily record cards patients receiving fluticasone propionate aqueous nasal spray had a significantly higher percentage of days on which they required no rescue medication (P < .009) and a higher percentage of days with an overall nasal blockage score on waking of < 2 (P < .013) when compared with placebo-treated patients. No other statistically significant results were found between the two active compounds.. Fluticasone propionate aqueous nasal spray 200 micrograms bid and beclomethasone dipropionate aqueous nasal spray 200 micrograms bid are effective in treating the symptoms of nasal polyps, with some evidence that fluticasone propionate aqueous nasal spray has a faster onset of action and is tolerated at least as well as beclomethasone dipropionate aqueous nasal spray at the same dose.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Polyps; Placebos

To test whether the use of fluticasone dipropionate nasal spray after endoscopic ethmoidectomy for multiple polyps is associated with a high incidence of infection. DESIGN. Randomized control study comparing the incidence of infection with the use of beclomethasone dipropionate or fluticasone propionate nasal spray after functional endoscopic sphenoethmoidectomy. Patients were followed up for 6 to 12 months.. Sixty patients with recurrent bilateral nasal polyps underwent functional endoscopic sphenoethmoidectomy and were then randomly allocated into 2 groups of 30 patients each. One group received beclomethasone dipropionate spray (100 micrograms in each nostril every 12 hours), and the other group received fluticasone propionate spray (100 micrograms/d in each nostril).. In the fluticasone propionate group, 6 patients (20%) developed acute gram-positive pansinusitis requiring hospitalization and discontinuation of treatment.. The use of fluticasone dipropionate aqueous nasal spray for the postoperative control of recurrent nasal polyps seems to be associated with a high incidence of acute pansinusitis.

Topics: Acute Disease; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Combined Modality Therapy; Endoscopy; Female; Fluticasone; Humans; Incidence; Male; Middle Aged; Nasal Polyps; Postoperative Care; Postoperative Complications; Sinusitis

Sinus surgery removes inflamed tissue, restores airflow, and improves delivery of medication into surgically opened spaces. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE. We aimed to compare EDS-FLU treatment responses in patients with recurrent symptoms after endoscopic sinus surgery (ESS) and patients who have never had sinus surgery.. Data were pooled from two large, controlled trials (NAVIGATE I and II) for exploratory analyses. Chronic rhinosinusitis symptoms, polyp grade, and quality-of-life measures were compared between patients with prior ESS and those without prior ESS.. Patients with prior ESS (exhalation delivery system-placebo [n = 53], EDS-FLU 186 μg [n = 52], and EDS-FLU 372 μg [n = 49]) and unoperated patients (exhalation delivery system-placebo [n = 108], EDS-FLU 186 μg [n = 108], and EDS-FLU 372 μg [n = 111]) treated with EDS-FLU reported similar and substantial benefits as measured by multiple symptom and quality-of-life/functioning outcomes (congestion score, 22-Item Sinonasal Outcomes Test [SNOT-22], Rhinosinusitis Disability Index [RSDI], Patient Global Impression of Change) and by nasal polyp grade. In previously operated patients, unlike surgery-naive patients, multiple outcomes (SNOT-22, RSDI, polyp grade) consistently showed numerically but not statistically greater responses to the higher dose.. Patients with recurrent symptoms after sinus surgery who were treated with EDS-FLU demonstrated significant symptom and quality-of-life improvement. Unlike unoperated patients, patients with prior ESS had a numerically but not statistically greater response to the higher dose of EDS-FLU (two sprays per nostril twice a day).

Topics: Chronic Disease; Endoscopy; Exhalation; Fluticasone; Humans; Nasal Polyps; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Treatment Outcome

Topics: Chronic Disease; Fluticasone; Humans; Nasal Polyps; Rhinitis; Sinusitis

Topics: Fluticasone; Humans; Nasal Polyps; Sinusitis

Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP).. Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC).. 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Topics: Chronic Disease; Endoscopy; Exhalation; Fluticasone; Humans; Nasal Polyps; Prospective Studies; Rhinitis; Sinusitis

Topics: Adrenal Cortex Hormones; Double-Blind Method; Exhalation; Fluticasone; Humans; Nasal Polyps; Rhinitis

Topics: Double-Blind Method; Exhalation; Fluticasone; Humans; Nasal Polyps

Topics: Adrenal Cortex Hormones; Double-Blind Method; Exhalation; Fluticasone; Humans; Nasal Polyps

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin-eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Biofilms; Chronic Disease; Drug Therapy, Combination; Female; Fluticasone; Humans; In Vitro Techniques; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Prospective Studies; Pseudomonas aeruginosa; Rhinitis; Sinusitis; Sodium Chloride; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae

Nasal and oral corticosteroid therapy is the ultimate treatment for sinonasal polyposis. Although there are numerous clinical studies regarding the factors associated with the formation of nasal polyposis, there is not enough literature on how these factors are influenced by steroid treatment. Twenty-one patients that had no prior medical therapy for nasal polyposis or had received medical therapy at least 6 months earlier were included in the study. Patients were treated with oral and nasal corticosteroid therapy. Nasal polyp biopsies were taken before and after medical treatment and immunohistochemical staining for cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were applied to the specimens. In this study, we tried to demonstrate the effects of corticosteroid therapy on nasal polyposis tissue immunohistochemically. There was no change at immunohistochemical expression level of COX-2; however, the decline of immunohistochemical expression levels of VEGF and iNOS was statistically significant. Short-term steroid therapy does not affect COX-2 level of the nasal polyposis tissue, but has an influence on iNOS and VEGF levels. Our findings were harmonious with those of the previous studies of the literature. Further studies are needed to demonstrate the long-term effects with a larger patient group.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adult; Androstadienes; Cyclooxygenase 2; Female; Fluticasone; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Polyps; Nitric Oxide Synthase Type II; Prednisolone; Vascular Endothelial Growth Factor A; Young Adult

NF-ĸB is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-ĸB inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than CRSwNP. The aim of study isto evaluate the ability of DHMEQ to reducethe inflammatory recruiters on CRSwNP and to compare its anti-inflammatory profile as a single-agent or in association with fluticasone propionate (FP).. nasal polyp fibroblasts were cultured in TNF-α enriched media. Cells were submitted to three different concentrations (1, 10 and 100nM) of either FP, DHMEQ or both. Inflammatory response was accessed by VCAM-1, ICAM-1 and RANTES expression (by RTQ-PCR) and protein levels by ELISA. Nuclear translocation of NF-ĸB was also evaluated.. both FP and DHMEQ inhibited inflammatory recruiters' production and NF-ĸB nuclear translocation. Interestingly, the anti-inflammatory effect from the association steroids plus DHMEQ was more intense than of each drug in separate.. DHMEQ seems efficient in modulating the inflammatory process in CRSwNP. The synergic anti-inflammatory effect of DHMEQ and steroids may be a promising strategy to be explored, particularly in the setting of steroid-resistant NP.

Topics: Active Transport, Cell Nucleus; Androstadienes; Anti-Inflammatory Agents; Benzamides; Cell Survival; Cells, Cultured; Chemokine CCL5; Cyclohexanones; Cytokines; Fibroblasts; Fluticasone; Gene Expression; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Nasal Polyps; NF-kappa B; Rhinitis; Sinusitis; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Transforming growth factor (TGF)-beta may play a significant role in nasal polyposis pathogenesis, possibly through fibroblast activation. We studied the effects of two TGF-beta isoforms (TGF-beta1 and TGF-beta2) on nasal polyposis fibroblasts by evaluating cell proliferation and differentiation into myofibroblasts. In addition, the inhibitory activity of different concentrations of fluticasone propionate (F.P.) was tested in this in vitro system. Primary nasal polyp tissue-derived fibroblasts were stimulated with different concentrations (1, 10 and 20 ng/ml) of TGF-beta1 and TGF-beta2 for different incubation periods (24, 48 and 72 h) and cell proliferation [3H thymidine ([3H]TdR) incorporation] and alpha-smooth muscle actin (alpha-SMA) expression (immunocytochemistry) was evaluated. The lowest concentration of TGF-beta1 (1 ng/ml) induced a significant increase in [3H]TdR incorporation at 48 and 72 h (p<0.05, each comparison), while in the presence of TGF-beta (10 ng/ml) and TGF-beta2 (1 ng/ml) the enhancement in cell proliferation was significant only after 48 h (p<0.05, each comparison with the unstimulated cells). In contrast, a significant increase in alpha-SMA expression was observed in the presence of the two highest concentration of both TGF-beta isoforms, at 48 and 72 h for TGF-beta1 (p<0.05, each comparison), but only at 72 h for TGF-beta2 (<0.05, each comparison). Finally, at all concentrations tested, F.P. significantly inhibited the TGF-beta1 and TGF-beta2-induced 3HTdR incorporation (p<0.01, each comparison) and the alpha-SMA expression (p<0.05, each comparison). Thus, in vitro different concentrations of TGF-beta1 and TGF-beta2 appear to sequentially stimulate primary nasal polyp tissue-derived fibroblast proliferation and myofibroblast differentiation. These activities are effectively inhibited by F.P.

Topics: Actins; Adult; Androstadienes; Anti-Inflammatory Agents; Cell Differentiation; Cell Proliferation; Female; Fibroblasts; Fluticasone; Humans; In Vitro Techniques; Male; Nasal Polyps; Thymidine; Transforming Growth Factor beta; Transforming Growth Factor beta1; Transforming Growth Factor beta2

Topical steroids did not affect expression of growth-related oncogene-alpha (GRO-alpha) in nasal polyps. The results of this study suggest roles for steroid-resistant gene expression in the pathogenesis of nasal polyps and point to the need for additional pharmacological strategies.. Infiltration of inflammatory cells is believed to play a role in the development of nasal polyps. GRO-alpha is a chemokine that recruits and activates neutrophils and also possesses growth stimulatory and angiogenetic properties. An increased presence of GRO-alpha has been demonstrated in nasal polyps compared with normal nasal tissue. In this study we evaluate the presence and expression levels of GRO-alpha in nasal polyps before and after glucocorticoid treatment.. Nasal polyps were surgically removed in patients before and 6 weeks after treatment with topically applied fluticasone. GRO-alpha gene expression and the presence of GRO-alpha peptide were detected in polyp tissue by means of in situ hybridization, quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.. Strong GRO-alpha gene expression and the presence of GRO-alpha peptide were seen in both the epithelium and stromal inflammatory cells of nasal polyps. No differences in gene expression levels in tissue homogenates were found when untreated polyp tissue was compared with polyps treated for 6 weeks with topically applied steroids.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Chemokine CXCL1; Chemokines; Chemokines, CXC; Female; Fluticasone; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Nasal Polyps; Oncogenes; Reverse Transcriptase Polymerase Chain Reaction

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 microg.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Eosinophils; ErbB Receptors; Fluticasone; Humans; Interleukin-8; Mucin 5AC; Mucins; Nasal Polyps; Neutrophil Infiltration; Tumor Necrosis Factor-alpha

To examine the influence of fluticasone propionate (FP) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts in vitro.. Fibroblasts derived from five nasal polyps were stimulated with tumor necrosis factor (TNF)-alpha in the presence of various concentrations of FP. The influence of FP on MMP production was assessed by examining the levels of MMP-2 and -9 in culture supernatants using ELISA. We also examined the influence of FP on MMP mRNA expression using reverse transcriptase polymerase chain reaction.. The addition of FP caused significant suppression of MMP-2 and -9 production from nasal polyp fibroblasts in response to TNF-alpha stimulation. MMP mRNA expression was also suppressed by the addition of FP to cell cultures. The minimum concentration of the agent required to cause suppression was 10(-5) M.. These results suggest that the inhibitory action of FP on tissue remodeling may underlie the clinical efficacy of corticosteroids in nasal polyposis.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Cells, Cultured; Female; Fibroblasts; Fluticasone; Gene Expression Regulation, Enzymologic; Humans; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Middle Aged; Nasal Polyps; RNA, Messenger; Tissue Inhibitor of Metalloproteinases

Nasal polyposis is treated by surgery and/or by medication but in parts without permanent remission. Fibroblasts and their proliferation are involved in the complex mechanism of polyp genesis. Therefore we have analysed the influence of 12 medications on fibroblasts from nasal polyps growing in vitro.. Nasal polyps, obtained during usual surgical procedure, are enzymatically digested and cultured in serum containing media. The growing cells are identified as fibroblasts using flow cytometry with a AS02-FITC antibody (Dianova). The analysis is achieved with 5 - 6 different fibroblast cultures in each medicament tested, mostly using concentrations of the active substance from 0.006 to 1.333 mg/ml. The fibroblasts are cultured 4 days in the presence of active substances or as controls. Finally the cells are trypsinated and counted.. Mometason, Beclomethason, Fluticason, Verapamil and Timolol are the group with the strongest reduction of fibroblasts. Mometason shows a reduction to 6 % of controls at a concentration of 30 micro g/ml whereas the reduction at this concentration amounts to 30 - 60 % in the other members of this group. Mesazalin, Methylprednisolone and Pentoxifylline demonstrate the smallest influence; Prednisolon-21-hydrogen-succinate, Pilocarpin, Piroxicam and Diclofenac show an effect on a middle level.. A strong reduction of fibroblasts from nasal polyps in vitro is possible with usual rhinological medicaments but also with unusual substances in this field.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Androstadienes; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Beclomethasone; Calcium Channel Blockers; Cells, Cultured; Culture Media; Diclofenac; Fibroblasts; Fluticasone; Glucocorticoids; Hematologic Agents; Humans; In Vitro Techniques; Mesalamine; Methylprednisolone; Mometasone Furoate; Muscarinic Agonists; Nasal Polyps; Pentoxifylline; Pilocarpine; Piroxicam; Prednisolone; Pregnadienediols; Time Factors; Timolol; Verapamil

To study the effects of intranasal FP on the expression of AQP-2 in nasal polyps.. Fourteen cases of type II phase 3 and 12 cases of type III nasal polyps were selected. FP were intranasally used in 7 cases of type II phase 3 and 6 cases of type III nasal polyps for 7 days before operation. The others, treated with nothing, were used as control. 26 nasal polyps were obtained and studied with immunohistochemical technique.. The volume of nasal polyps in FP-using group became smaller. Both the number of AQP-2 positive cells and the area density were significantly lower in the FP-using group than in the control group (P < 0.01).. Under the action of intranasal FP the expression of AQP-2 reduced, so is the volume of nasal polyps. It indicated that AQP-2 contributed to edema of nasal polyps and FP may lesson edema through changing the expression of AQP-2.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Aquaporin 2; Aquaporins; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Budesonide; Child; Female; Fluticasone; Humans; Male; Mometasone Furoate; Nasal Polyps; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Singapore; Sinusitis; Triamcinolone Acetonide

Besides being highly effective in the treatment of allergic and nonallergic rhinitis with eosinophilia, intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. We evaluated the ability of fluticasone propionate to downregulate fibroblast functions related to nasal inflammation and remodeling.. Primary nasal polyp tissue-derived fibroblasts were stimulated with tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 or basic fibroblast growth factor (bFGF) in the presence of fluticasone propionate (0.1-100 nM). Fibroblast proliferation, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression and eotaxin release were then evaluated.. As compared with unstimulated cultures, a significant increase in fibroblast proliferation was observed when the cells were stimulated with bFGF (p < 0.05), but not with TNF-alpha or IL-4 (p > 0.05). TNF-alpha induced an upregulation of ICAM-1 expression (p < 0.05), which was not seen in fibroblasts cultured in the presence of IL-4 or bFGF. No changes in VCAM-1 expression were induced by TNF-alpha, IL-4 or bFGF, whereas both TNF-alpha and IL-4 increased eotaxin release (p < 0.05). Both bFGF-induced fibroblast proliferation and TNF-alpha-induced ICAM-1 expression were significantly reduced by fluticasone, starting at the dose of 1 and 10 nM, respectively (p < 0.05). Fluticasone at concentrations of 1-100 nM effectively inhibited eotaxin release by TNF-alpha- or IL-4-stimulated fibroblasts (p < 0.05).. The pharmacologic activity of fluticasone in patients with chronic upper airway inflammatory disease may include inhibition of resident fibroblast functions involved in airway inflammation and remodeling.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Cell Division; Chemokine CCL11; Chemokines, CC; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factor 2; Fibroblasts; Flow Cytometry; Fluticasone; Glucocorticoids; Humans; Intercellular Adhesion Molecule-1; Interleukin-4; Male; Nasal Polyps; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Nasal polyposis disease is an inflammatory disorder with intense eosinophilic infiltration of respiratory mucosa that is often difficult to control with topical steroids. Recent evidence suggests that overexpression of the glucocorticoid receptor splice variant GRbeta in inflammatory cells might contribute to steroid insensitivity in diseases such as asthma.. The purposes of this investigation were to determine whether nasal polyp (NP) inflammatory cells overexpress GRbeta and to examine whether GRbeta overexpression is associated with insensitivity to the potent topical steroid fluticasone propionate (FP).. Biopsies were obtained from 10 subjects with NPs before and 4 weeks after treatment with intranasal FP. Middle turbinates biopsies from 6 healthy, nonallergic subjects served as normal controls. Biopsies were immunostained for inflammatory cell markers as well as GRbeta and probed for various cytokine mRNA. The anti-inflammatory response to FP was examined in relation to pretreatment levels of GRbeta expression.. The total numbers of inflammatory cells were increased in NPs. The percentage of inflammatory cells expressing GRbeta was also increased (40.5% +/- 19.2% vs 16.1% +/- 4.0%, P =.009). GRbeta expression in NPs was almost exclusive to T lymphocytes, eosinophils, and macrophages. An inverse correlation was observed between the baseline inflammatory cell GRbeta expression and the reduction after FP treatment in EG2-positive eosinophils, CD4-positive T lymphocytes, endothelial VCAM-1 expression, and IL-4 mRNA-positive cells. NPs that were "FP-insensitive" in terms of suppression of eosinophil numbers (major basic protein-positive) had a significantly greater percentage of GRbeta-positive inflammatory cells, a higher ratio of GRbeta-positive/GRalpha-positive cells, and increased numbers of GRbeta-positive eosinophils and macrophages in comparison with those that were "FP-sensitive." "FP-insensitive" NPs also demonstrated a higher percentage of IL-5-positive inflammatory cells expressing GRbeta before and after FP treatment.. GRbeta expression appears to be a marker of steroid insensitivity in NPs. Expression of GRbeta by NP inflammatory cells, particularly T cells and eosinophils, might render them resistant to suppression by topical steroids and thereby contribute to persistent NP inflammation.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Drug Resistance; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Interleukin-5; Leukocyte Count; Male; Nasal Polyps; Receptors, Glucocorticoid; T-Lymphocytes

A variety of corticosteroid delivery systems have been considered for the treatment of nasal polyposis. Safety considerations favour local delivery of the drug to the nasal cavity. No topical delivery system is entirely without problems, however, and formulations must address issues of microbiological quality, drug stability, reproducible drug delivery and adequate drug distribution at site, while also offering environmental and patient acceptability. Fluticasone propionate has been formulated in a new nasal drop preparation. As a highly water-insoluble compound, the active fluticasone propionate requires micronization to an optimal particle size and subsequent dispersion with a surface-active wetting agent. The product is presented in a unit dose low-density polyethylene container, manufactured by a blow-fill-seal process and stored in an aluminium foil overwrap. Micronized active has been used to promote optimal local drug delivery, and excipients have been selected for low irritancy potential and high formulation stability. There is no microbiological risk with fluticasone propionate unit dose nasal drops 400 microg and therefore no need to include a preservative in the preparation. They provide a convenient and effective treatment option for patients with nasal polyposis.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Chemistry, Pharmaceutical; Drug Packaging; Drug Stability; Fluticasone; Humans; Nasal Polyps

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reaction, However, the mechanism of accumulation of these cells has not yet been well clarified. We hypothesized that cytokines generated from the nasal epithelial cells contributed to the accumulation of these cells in the nasal epithelial layer. Recently tumor necrosis factor (TNF) was shown to promote polymorphonuclear neutrophils and eosinophils migration. And also TNF increased eosinophil binding to vascular endothelial cells. In this in vitro study we examined whether or not nasal epithelial cells can produce TNF-alpha and also whether or not glucocorticosteroid fluticasone propionate (FP) can modulate TNF-alpha production from nasal epithelial cells. Nasal epithelial cells constitutively produce TNF-alpha in accordance with the nasal epithelial cells' number and this was substantially increased in the state of nasal epithelial cell's proliferating. FP significantly reduced the level of TNF-alpha in the supernatant of cultured nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days caused significant reduction of TNF-alpha level in the supernatant of cultured nasal epithelial cells during a further period of 6 days without FP. These data support the concept that structural cells play an active role in the control of allergic and related inflammatory processes.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Cells, Cultured; Depression, Chemical; Epithelium; Female; Fluticasone; Humans; Male; Nasal Mucosa; Nasal Polyps; Rhinitis, Allergic, Perennial; Tumor Necrosis Factor-alpha