fluticasone and Rhinitis--Allergic--Perennial

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Benzimidazoles; Butyrophenones; Cyproheptadine; Fluticasone; Histamine H1 Antagonists; Humans; Omalizumab; Phthalazines; Piperidines; Pregnenediones; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

During the last few years, fixed combinations of intranasal antihistamines and corticosteroids have been introduced for treatment of allergic rhinitis. The aim of this systematic review was to assess recent patents and clinical evidence for fixed combinations of intranasal antihistamines and intranasal corticosteroids in allergic rhinitis. Data base searches revealed that intranasal combinations of the antihistamine azelastine with the corticosteroids mometasone furoate, ciclesonide and fluticasone propionate, respectively, have been patented. Four randomized, double-blinded, parallel-group, placebo-controlled, multicenter trials sponsored by the manufacturer evaluated the fixed combination of intranasal azelastine 125 µg and fluticasone propionate 50 µg administered as one dose per nostril b.i.d. in patients with moderate-to-severe symptomatic allergic rhinitis ≥ 12 years of age. Three of the studies were published as a meta-analysis which found the fixed combination of azelastine and fluticasone propionate statistically significantly more efficacious in reducing baseline total nasal symptom score by 5.7 as compared to azelastine (4.4; P < 0.001), fluticasone propionate (5.1; P < 0.001) and placebo (3.0; P < 0.001). The findings were supported by secondary assessments of scores of specific nasal and ocular symptoms. Pharmacokinetic studies have revealed no drug-drug interactions but a discrete increase in bioavailability of fluticasone propionate which was considered clinically unimportant. Further efficacy and quality-of-life studies of combination products of nasal antihistamines and corticosteroids are needed, especially, in primary care settings and in children before fixed combination treatment can be considered first line therapy in allergic rhinitis. Fixed combination treatment of azelastine and fluticasone propionate may offer additional benefit to selected populations of adolescents and adults with moderate-to-severe symptoms.

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Androstadienes; Animals; Drug Combinations; Evidence-Based Medicine; Fluticasone; Histamine Antagonists; Humans; Mometasone Furoate; Patents as Topic; Phthalazines; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Topics: Allergens; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Bronchial Provocation Tests; Bronchodilator Agents; Environmental Exposure; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Animals; Anti-Allergic Agents; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Chronic Disease; Diagnosis, Differential; Drug Administration Schedule; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Nurse Practitioners; Nurse's Role; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Triamcinolone

Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized.. To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia.. Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea.. Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 microg or 400 microg compared with placebo; thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups, respectively, to -64 in the placebo group. The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were similar to changes seen in the total population; mean change in TNSS for the FP 400 microg group was somewhat greater than changes seen in the total population.. Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Skin Tests

Topical administration of corticosteroids can reduce the total dose of corticosteroid required to treat the patient and minimize side effects. This logic has led to the development of intranasal corticosteroids (INCS) for allergic and perennial rhinitis. The second generation of these compounds includes beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. There is evidence that the INCS are effective in rhinitis; however, there is concern about the potential for these compounds to cause growth suppression. In one study, beclomethasone dipropionate significantly reduced growth in children; however, treatment of children with mometasone furoate nasal spray for 1 year showed no signs of growth suppression. It is evident that the differences among INCS lie in their pharmacokinetics. Structural differences among the various INCS influence their metabolism. The goal of INCS therapy is to have a high ratio of topical to systemic activity. The drug delivery device, absorption of the drug, and drug distribution all contribute to effective topical activity of an INCS. In addition, individual drug metabolism and elimination (half-life and drug clearance) also contribute to the therapeutic index of a drug. Overall, the second-generation INCS cause minimal systemic effects at recommended doses.

Topics: Absorption; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Child; Drug Delivery Systems; Fluocinolone Acetonide; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship; Tissue Distribution; Triamcinolone Acetonide

Triamcinolone is a commonly used synthetic corticosteroid that has recently been tested in a large clinical trial for chronic obstructive pulmonary disease and shown to have some benefits. To our knowledge, there are no reviews of the pharmacotherapy of triamcinolone. This review has a brief overview of the pharmacology of triamcinolone, followed by a discussion of the clinical trials with triamcinolone. Triamcinolone is used in the treatment of respiratory inflammation, rheumatoid arthritis and a variety of other inflammatory conditions.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Astemizole; Asthma; Child; Clinical Trials as Topic; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Fluticasone; Humans; Injections, Intramuscular; Loratadine; Lung Diseases, Obstructive; Macular Degeneration; Molecular Structure; Nasal Mucosa; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship; Triamcinolone

Fluticasone propionate is an established corticosteroid administered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma. Mometasone furoate, a closely related corticosteroid currently available in an intranasal formulation, is being investigated in an oral inhalation formulation for the treatment of asthma.. This article reviews available data on the comparative structure-activity relationships, chemistry, pharmacology, pharmacokinetics, and systemic bioavailability of fluticasone propionate and mometasone furoate to assess whether claims of differences in the absolute systemic bioavailability of the 2 compounds are supported by the published literature.. Information for this review was identified through a MEDLINE search of the literature from 1966 to the present that contained the term mometasone or fluticasone. The resulting list was narrowed by excluding articles dealing with dermatologic applications. A systematic review was conducted of the identified literature pertaining to the molecular structure, topical potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agents. Additionally, the pharmacology of the 2 moieties was assessed by a review of the available literature on receptor binding affinity, transactivation and transrepression potency, and inhibition of inflammatory-cell cytokine expression.. Based on the available data, fluticasone propionate and mometasone furoate have similar physicochemical properties and structure-activity relationships. When administered intranasally, mometasone furoate is reported to have comparable relative systemic bioavailability to that of fluticasone propionate (mean plasma area under the curve, 123 pmol x h/L vs 112 pmol x h/L, respectively). When administered as a single dose by dry powder inhaler, orally inhaled fluticasone propionate is reported to have a total systemic bioavailability of approximately 17%, whereas that of mometasone furoate is reported to be < 1%. However, the mometasone furoate bioavailability study that reported the latter value used lower drug doses and a less sensitive assay than the fluticasone propionate bioavailability study. When multiple-dose data were used, mometasone furoate had an estimated 11% systemic bioavailability, similar to that of fluticasone propionate.. Inhaled fluticasone propionate and mometasone furoate appear to have comparable potential systemic absorption and, based on the total systemic bioavailabilities of the parent compounds, have a low potential for systemic side effects at the recommended clinical doses. However, in the case of mometasone furoate, the contribution of the active metabolites to systemic effects has not been adequately assessed.

Topics: Administration, Intranasal; Androstadienes; Biological Availability; Cytokines; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Receptors, Glucocorticoid; Rhinitis, Allergic, Perennial; Time Factors

Allergic rhinitis manifests itself clinically due to the local release of mediators from activated cells within the nasal mucosa. Treatment strategies aim either to reduce the effects of these mediators on the sensory neural and vascular end organs, or to reduce the tissue accumulation of the activated cells that generate them. Corticosteroids intervene at a number of steps in the inflammatory pathway, and, by reducing the release of cytokines and chemokines, inhibit cell recruitment and activation. These effects are evident both in vivo and in vitro. While antihistamines also have some anti-inflammatory effects in vitro, these require higher concentrations than with corticosteroids and are not consistently reproduced in vivo. In addition, although antihistamines and corticosteroids might appear to have complementary mechanisms of action, clinical trials suggest that their co-administration does not confer any additional long-term benefits compared with that achieved with corticosteroids alone. Topical corticosteroids are therefore the preferred anti-inflammatory therapy for persistent allergic rhinitis.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Cell Degranulation; Cytokines; Fluticasone; Histamine H1 Antagonists; Humans; Mast Cells; Rhinitis, Allergic, Perennial; T-Lymphocytes

Topical intranasal corticosteroids (INS) are the most effective treatment for allergic rhinitis and are being increasingly prescribed to children. Due to the potent inhibition of childhood growth seen with oral corticosteroids, it is important to examine whether INS could have similar effects. The evidence available suggests that some INS, such as beclomethasone dipropionate (BDP), may slow growth when used regularly for prolonged periods. However, newer INS such as fluticasone propionate (FP) and mometasone furoate, which have substantially reduced bioavailability via gastrointestinal absorption, are unlikely to do so. Well-designed prospective studies are needed to distinguish those INS with reduced or absent effects on growth. In practice, choosing an INS which optimises the ratio of therapeutic effect to systemic bioavailability will probably reduce the risk of growth suppression to a negligible level.

Topics: Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Child; Child, Preschool; Fluticasone; Growth; Humans; Rhinitis, Allergic, Perennial

Intranasal steroids (INSs) are established as first-line treatment for allergic rhinitis. Extensive use of INSs with few reported adverse events supports the safety of these medications. Nevertheless, the prescription of more potent INSs for consistent and more prolonged use to younger and older patients, often in combination with inhaled corticosteroids, justifies the careful examination of their potential adverse systemic effects. Systemic bioavailability of INSs, by way of nasal and intestinal absorption, can be substantial; but current INSs vary significantly in their degree of first-pass hepatic inactivation and clearance from the body of the swallowed drug. For safety studies of INSs, distinguishing detectable physiologic perturbations from important adverse events is aided by an understanding of normal endocrine physiology and the methods used to test these systems. A review of available information indicates that (1) sensitive tests can measure the effects of INSs on biologic feedback systems, but they do not accurately predict clinically relevant adverse effects; (2) the primary factors that influence the relationship between therapeutic and adverse systemic effects of INSs are dosing frequency and efficiency of hepatic inactivation of swallowed drug; (3) INS treatment in recommended doses does not cause clinically significant hypothalamic-pituitary-adrenal axis suppression; (4) growth suppression can occur with twice-daily administration of certain INSs but does not appear to occur with once-daily dosing or with agents with more complete first-pass hepatic inactivation; (5) harmful effects of INSs on bone metabolism have not yet been adequately studied but would not be expected with the use of an INS dose and dosing frequency that do not suppress basal hypothalamic-pituitary-adrenal axis function or growth; and (6) these conclusions apply to INS treatment alone and in recommended doses-the risk of adverse effects in individual patients who are treated with INSs is increased by excessive dosing or concomitant inhaled corticosteroid or other topical corticosteroid therapy.

Topics: Administration, Intranasal; Androstadienes; Beclomethasone; Budesonide; Endocrinology; Fluocinolone Acetonide; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Steroids; Triamcinolone Acetonide

The anti-inflammatory activity of corticosteroids has prompted the exploration of their use in the treatment of allergic rhinitis. The development of intranasal steroids has resulted in several agents with quick actions, localized effects, and great efficacy in the treatment of seasonal allergic rhinitis and the prophylactic management of perennial rhinitis. This article presents a concise review of the preclinical and clinical evidence with these new agents and provides data-based guidance for the selection of optimal agents. The survey reveals that mometasone furoate, a new inhaled steroid with topical activity, has the greatest binding affinity for the glucocorticoid receptor, followed by fluticasone propionate, budesonide, triamcinolone acetonide, and dexamethasone. Mometasone furoate also has strong anti-inflammatory activity, with IL-4 and IL-5 inhibition activities equivalent to those of fluticasone propionate. Clinically, both mometasone furoate and fluticasone propionate appear to be well tolerated, to have quick onsets of action, and to be equivalent in efficacy in the treatment of seasonal allergic and perennial rhinitis. Of the intranasal steroids currently available, mometasone furoate has been shown to have the least systemic availability and, consequently, is expected to have the fewest systemic side effects. Some suppression of overnight cortisol levels has been reported with fluticasone propionate (indicative of hypothalamic-pituitary-adrenal axis suppression).

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Biological Availability; Clinical Trials as Topic; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Drug Evaluation; Fluticasone; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone propionate (FP) is a new topical corticosteroid spray for the treatment of allergic rhinitis and asthma. FP has been shown to be effective for the treatment of adult and pediatric asthma, even at rather low doses (25 microg twice daily [b.i.d.]); many studies in asthma have shown clinical efficacy of fluticasone at half the dose of the comparison steroid (such as beclomethasone dipropionate [BDP] or budesonide [BUD]). However, exact dose comparisons cannot be made because dose-ranging comparison studies have not been done. Studies in allergic rhinitis in children and adults have shown good efficacy in FP-treated patients at a dose of 200 microg once daily (o.d.), intranasally. In summary, FP is effective in both asthma and allergic rhinitis.. FP has minimal systemic activity because the portion of drug that is swallowed is not absorbed from the gut. Thus, the amount available for systemic activity is only that which is absorbed through the nasal mucosa (in the treatment of rhinitis) or through the alveoli of the lungs (in the treatment of asthma). When laboratory assays of adrenal function or bone formation are measured, FP and other inhaled corticosteroids can be shown to cause suppression of these markers, especially at high doses. There have been no consistent reports of clinical adrenal suppression or osteoporosis caused by FP. In summary, the risk-benefit ratio of FP at the usual doses (therapeutic ratio) is very favorable. High doses may show evidence of suppression of the hypothalamic pituitary axis as measured by in vitro tests, but evidence of corresponding clinical adverse effects is lacking.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Fluticasone; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Risk Assessment

Allergic rhinitis (AR) is a common allergic disease. It affects people worldwide and traditional Chinese medicine is becoming popular among AR patients because it has a definite clinical effect and there are few adverse reactions. Lung qi deficiency and cold syndrome (LQDCS) is a frequent type of AR, and the Chinese herbal medicine bimin decoction (BMD) is prescribed for it. This study compared the clinical efficacy of BMD for AR patients with LQDCS to the conventional medicine loratadine and fluticasone nasal spray.. The study was an open-label non-inferiority randomized controlled trial. A total of 108 AR patients with LQDCS aged 19 to 60 were randomly allocated in a 1:1 ratio to the BMD group or the control group by the central computer system in Beijing Hospital of Traditional Chinese Medicine from January 2017 to April 2018. In total, 98 participants completed the study (BMD group n = 51 and control group n = 47). Patients in the BMD group received BMD while those in the control group received fluticasone nasal spray and loratadine tablets for 4 weeks. The primary outcome was the change in the Total Nasal Symptom Score (TNSS) between the baseline and the end of treatment. Changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal resistance, and acoustic rhinometry parameters were secondary outcomes. All side effects due to the treatments were recorded.. After the 4-week treatment, the total TNSS was significantly reduced in both groups compared to the baseline (P <  0.05). No significant between-groups differences were observed for changes in TNSS scores [- 0.298 (95% confidence interval -0.640 to 0.140)], which was within the defined non-inferiority margin. RQLQ in both groups decreased significantly (P <  0.001) from baseline, though a more obvious reduction was observed for the BMD group (P <  0.001). There were no significant differences in nasal resistance, nasal volume, or nasal minimum cross-sectional area between groups after treatment (P > 0.05).. These findings indicate that BMD helps relieve the symptoms of perennial AR and improves rhinitis-related quality of life. Our study indicates that BMD is non-inferior to loratadine tablets and fluticasone nasal spray for AR patients with LQDCS.. Chinese Clinical Trial Registry, ChiCTR-INR-16010063. Registered on 2 December 2016.

Topics: Adult; Anti-Allergic Agents; Drugs, Chinese Herbal; Female; Fluticasone; Humans; Loratadine; Male; Middle Aged; Nasal Obstruction; Nasal Sprays; Quality of Life; Rhinitis, Allergic, Perennial; Sneezing; Surveys and Questionnaires; Treatment Outcome; Young Adult

Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR). Triamcinolone acetonide is a nasal corticosteroid preparation indicated for the treatment of seasonal and perennial AR (PAR) in different countries worldwide.. In order to determine the efficacy of triamcinolone acetonide in the treatment of PAR, the non-inferiority of triamcinolone acetonide to fluticasone propionate was assessed in Russian adults.. In this randomized, double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial, a total of 260 patients with persistent PAR were randomized to receive either triamcinolone acetonide or fluticasone propionate nasal sprays for 4 weeks. The efficacy in symptom control was evaluated using the reflective total nasal symptom score (rTNSS) from baseline (day 0) to day 28. Safety was assessed through the reporting of adverse events.. The rTNSS mean values decreased from baseline to the end of study treatment (day 28) in both groups: -8.2 ± 3.0 in the triamcinolone acetonide arm versus -8.0 ± 2.8 in the fluticasone propionate arm. The mean difference between the groups (triamcinolone acetonide - fluticasone propionate) for rTNSS change from baseline was -0.2 (95% confidence interval -0.89 to 0.54), with an upper confidence limit of 0.54, which is lower than the non-inferiority margin of 0.8. Triamcinolone acetonide was well tolerated, with no difference in adverse event occurrence compared with fluticasone propionate.. Triamcinolone acetonide proved to be non-inferior to fluticasone propionate in adult patients with PAR; both treatments decreased rTNSS values and showed a good safety profile.

Topics: Administration, Intranasal; Adult; Allergens; Anti-Allergic Agents; Female; Fluticasone; Humans; Male; Quality of Life; Rhinitis, Allergic, Perennial; Skin Tests; Treatment Outcome; Triamcinolone Acetonide

Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR).. We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM-induced murine model of allergic airway disease.. Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-γ, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo.. A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN-γ had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability.. We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR.

Topics: Adult; Animals; Anti-Inflammatory Agents; Biomarkers; Case-Control Studies; Dextrans; Female; Fluorescein-5-isothiocyanate; Fluticasone; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Nasal Mucosa; Occludin; Permeability; Pyroglyphidae; Real-Time Polymerase Chain Reaction; Rhinitis, Allergic, Perennial; Tight Junctions; Zonula Occludens-1 Protein

To assess the applicability of the Peak Nasal Inspiratory Flow (PNIF) curves in follow-up of children in the treatment of allergic rhinitis.. Prospective study of 40 patients with AR, grouped in corticosteroid spray versus physiological saline solution use. Follow up for 10 weeks through clinical score and PNIF percentages in relation to the reference curves, with was-out at week 8. Statistical assessment of the effect of treatment on variation of PNIF and clinical score was calculated by ANOVA model and Multiple Comparison of Means Test - Least Significant Difference.. There was a statistically significant influence of the group, time and interaction between time and group on PNIF percentages. Throughout follow up, patients from the treatment group had mean PNIF percentages significantly higher than the placebo group. Clinical score results also demonstrated a statistically significant influence between the groups, time and interaction between time and group.. Increase in PNIF percentage values observed in children treated with intranasal corticosteroids revealed the applicability of PNIF curves in their follow up.

Topics: Adolescent; Airway Resistance; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Inhalation; Inspiratory Capacity; Male; Prospective Studies; Reference Values; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Treatment Outcome

Various studies have investigated the efficacies of mometasone furoate monohydrate (MFM) and fluticasone propionate (FP) nasal sprays for adults. However, research on their effectiveness for children is limited. This study compares the efficacies of MFM and FP nasal sprays in pediatric patients with perennial-allergic rhinitis.. For this study, 94 perennial allergic rhinitis patients aged 6-12 years were randomly assigned to two treatment groups: an MFM group and an FP group. Treatment was provided for 4 weeks. The effects of the two agents were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and total symptom scores (TSSs). Nasal-peak expiratory flow rates and eosinophil percentage in nasal smears were also compared between the two groups.. Patients in the MFM group exhibited significant improvement in their TSS (t = -2.65, p < 0.05). A detailed TSS analysis showed MFM to be more effective for relieving nasal symptoms, whereas FP was more effective for relieving non-nasal symptoms. Patient questionnaire scores suggested a significant reduction in symptoms for both the MFM (t = -7.23, p < 0.01) and FP (t = -5.43, p < 0.01) groups. The flow rate test results indicated significant improvements in the MFM group (t = 2.27, p < 0.05).. Following the 4-week therapy, MFM provided greater improvement compared to FP for symptoms of childhood perennial-allergic rhinitis. Based on their TSSs, the MFM group experienced more effective relief of nasal symptoms, whereas the FP group experienced more effective relief of non-nasal symptoms.

Topics: Allergens; Androstadienes; Animals; Anti-Allergic Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Dust; Female; Fluticasone; Follow-Up Studies; Humans; Male; Mites; Mometasone Furoate; Nasal Sprays; Patient Satisfaction; Pregnadienediols; Prospective Studies; Quality of Life; Rhinitis, Allergic, Perennial; Risk Assessment; Severity of Illness Index; Treatment Outcome

β(2)-Agonists have previously been shown to be effective inhibitors of mediator release from airway mucosal mast cells.. To evaluate the effects of intranasal salmeterol and fluticasone propionate alone and in combination on the response to nasal adenosine monophosphate (AMP) challenge to assess mast cell activation.. Twenty-three patients with persistent allergic rhinitis completed a randomized, double-blind, placebo-controlled, 4-way crossover trial. They received once daily treatment with placebo, salmeterol, 50 μg, fluticasone propionate, 500 μg, or fluticasone propionate and salmeterol combination, 500/50 μg, delivered via an antistatic spacer with nasal adapter for 1 week each, with trough measurements being made 12 hours after the first and last dose. The primary outcome was the maximum percentage decrease in peak nasal inspiratory flow after nasal AMP challenge.. For the primary outcome there was significant protection after single and long-term dosing with fluticasone alone and fluticasone-salmeterol combination, whereas salmeterol alone only afforded protection after the first dose. Fluticasone-salmeterol combination and fluticasone but not salmeterol conferred significant chronic dosing effects on secondary outcomes of nasal symptoms and disease-specific quality of life. There was no potentiation of the response to fluticasone by salmeterol on any outcomes when given in combination.. Chronic dosing with fluticasone but not salmeterol confers anti-inflammatory activity against nasal AMP challenge, but there was no potentiation of fluticasone when given in combination with salmeterol. Thus, salmeterol may not be an effective treatment for use in allergic rhinitis.. clinicaltrials.gov Identifier: NCT01388595.

Topics: Adenosine Monophosphate; Administration, Intranasal; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Rhinitis, Allergic, Perennial; Salmeterol Xinafoate; Treatment Outcome

Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid.. Twenty five participants were randomized to receive two weeks of 100 microg/day (Low dose) or 500 microg/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 microg/day with intranasal fluticasone 200 microg/day (Combined) in a double-blind cross-over fashion.. Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC(20) from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, -0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV(1) and asthma quality of life.. High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function.

Topics: Administration, Inhalation; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Breath Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Young Adult

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

Guidelines for the treatment of patients with allergic rhinitis (AR) recommend intranasal corticosteroids as first-line therapy. In clinical trials, however, only 50% of patients obtain excellent symptom control.. To evaluate the effectiveness of montelukast add-on therapy in patients with perennial AR (PAR) who have incomplete relief of symptoms after 2 weeks of treatment with intranasal fluticasone propionate.. We performed a 4-week parallel, randomized, double-blind, placebo-controlled trial. One hundred two patients with a history of PAR and a positive skin test reaction to perennial allergens were recruited. They completed the Rhinitis Quality of Life Questionnaire (RQLQ) and were given intranasal fluticasone propionate, 200 microg daily. They were asked to complete symptom diary cards twice daily. After 2 weeks of treatment, patients with a mean total nasal symptom score of at least 4 during the past week (n = 54) were randomized to receive either montelukast (n = 28) or placebo (n = 26) in addition to the continued use of fluticasone propionate. At weeks 3 and 4, the RQLQ was completed again and symptom diary cards were collected.. Compared with baseline, there were significant improvements in almost all domains of the RQLQ while taking fluticasone propionate (P < .001). A similar trend was observed for nasal symptom scores. After randomization to receive montelukast or placebo, there were no significant differences in RQLQ measures or nasal symptom scores between the groups during the 2 weeks of combination therapy.. The addition of montelukast to an intranasal corticosteroid for the treatment of PAR with residual symptoms is no more effective than is placebo.

Topics: Acetates; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Chemotherapy, Adjuvant; Cyclopropanes; Feasibility Studies; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Quality of Life; Quinolines; Rhinitis, Allergic, Perennial; Skin Tests; Sulfides; Surveys and Questionnaires; Treatment Outcome

There are few data on the clinical equivalence of different nasal corticosteroids in persistent allergic rhinitis (AR). Studies measuring plasma concentrations after a single dose may not predict relative systemic bioactivity at steady state.. To compare a test formulation of fluticasone propionate with the innovator using a noninferiority design.. Twenty-three patients with persistent AR were randomized to completion in a double-blind, placebo-controlled, crossover manner to receive the formulations at 200 microg/d for 4 weeks, with baselines measured after 2-week run-in and washout periods. The primary outcome measure was the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) score.. Both formulations produced significant improvements in MiniRQLQ scores as change from baseline (P < .001), with a nonsignificant mean difference (test vs innovator) of -0.06 U (95% confidence interval [CI], -0.41 to 0.52 U) and the lower bound of the 95% CI being above the predefined noninferiority limit of -0.7 U. Both formulations produced significant improvements in peak nasal inspiratory flow rates as change from baseline (P < .01), with a nonsignificant mean difference of 0.5 L x min(-1) (95% CI, 9.8 to 10.8 L x min(-1)). There were also significant reductions in total nasal symptom scores (P < .01), with a nonsignificant mean difference of 0.4 U (95% CI, 0.3 to 1.1 U). No significant suppression of the 10-hour overnight urinary cortisol to creatinine ratio was seen with either formulation.. The test formulation was noninferior to the innovator for the primary outcome of MiniRQLQ score. The secondary efficacy and safety end points also support the interchangeability of the 2 formulations.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Allergic Agents; Case-Control Studies; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Rhinitis, Allergic, Perennial; Surveys and Questionnaires

To evaluate the safety and efficacy of once-daily (QD) fluticasone furoate (FF) nasal spray in children with perennial allergic rhinitis (PAR).. A global, randomized, double-blind, placebo-controlled study.. Pediatric patients (aged 2-11 years; n = 558) with PAR received once-daily placebo, FF 110 microg, or FF 55 microg for 12 weeks. Efficacy was evaluated by nasal symptom scores. General safety and corticosteroid-specific safety (nasal and ophthalmic examinations, and hypothalamic-pituitary-adrenal assessments) were assessed.. No findings of clinical concern were identified from the safety assessments. For primary efficacy analysis of mean change from baseline over the first 4 weeks of treatment in daily reflective total nasal symptom score, FF 55 microg demonstrated significant improvement (P = 0.003) compared with placebo; however, the improvement for FF 110 microg versus placebo did not reach statistical significance (P = 0.073).. FF QD was well tolerated and demonstrated efficacy in children aged 2 to 11 years with PAR.

Topics: Administration, Oral; Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Male; Rhinitis, Allergic, Perennial; Treatment Outcome

Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR).. The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR.. This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment.. Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF.. In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Mucosa; Odorants; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sensation; Sensory Thresholds; Surveys and Questionnaires; Taste; Treatment Outcome; United States

There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases.. The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days.. A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared.. Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators.. A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.

Topics: Adenosine A2 Receptor Antagonists; Adenosine A3 Receptor Antagonists; Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Betamethasone; Biomarkers; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Interleukin-5; Interleukin-8; Male; Middle Aged; Nasal Lavage Fluid; Nasal Provocation Tests; Placebos; Purinergic P1 Receptor Antagonists; Purines; Rhinitis, Allergic, Perennial; Tetrazoles; Time Factors; Treatment Failure; Tryptases

Allergic rhinitis (AR) and asthma coexist frequently and a dual treatment is recommended by prescribing topical nasal plus oral inhaled corticosteroids. The purpose of this study was to assess the efficacy of a nasally inhaled corticosteroid aiming at concomitant control of AR and asthma. A controlled trial was conducted among 60 patients with AR and asthma, aged 6-18 years, who were randomized into two groups. During 8 weeks, the experimental group (30 patients) received exclusively fluticasone propionate hydrofluoroalkane (FP-HFA) inhaled through the nose (mouth closed) using a large volume spacer attached to a face mask. The comparison group (30 patients) received a nasal spray of isotonic saline plus oral inhalation of FP-HFA through a mouthpiece attached to the same spacer. Clinical scores for AR and asthma, nasal inspiratory peak flow (NIPF), and spirometry were assessed by blinded observers. There was a significant improvement in AR scores and NIPF in the experimental group (P or= 0.20). Prebronchodilator FEV(1) (% predicted value) improved by 10% in both groups, comparing values at inclusion with those obtained at the end of follow up. Our results suggest that nasally inhaled FP-HFA through a spacer may control AR and asthma in children and adolescents. This approach is likely to result in higher compliance, lower costs, and fewer side effects.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Rhinitis, Allergic, Perennial; Treatment Outcome

The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER).. Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios.. Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg, and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose.. FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER.

Topics: Adenosine Monophosphate; Adolescent; Adult; Aged; Androstadienes; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Provocation Tests; Quality of Life; Rhinitis, Allergic, Perennial; Treatment Outcome

Despite constant exposure to micro-organisms and other immunogenic environmental factors, relatively very few immunological responses are initiated in the nasal mucosa. Although several mechanisms could play a role in maintaining this immune suppressive milieu, none of them have been validated. Previous data from our group suggested that locally produced interleukin (IL)-10 could be involved in maintaining local homeostasis.. To investigate the role of epithelial IL-10 expression in the manifestation of allergic symptoms, we used immunohistochemistry to study the expression of IL-10 in the nasal epithelium of healthy individuals and house dust mite allergic patients. In the allergic patients, we determined potential correlations of epithelial expression with allergic symptoms, both at baseline and after allergen provocation.. IL-10 is expressed in the basal and differentiated epithelial cells of both healthy individuals and allergic rhinitis patients. In the allergic individuals, there is a strong negative correlation at baseline between the epithelial expression level of IL-10 and rhinorrhoea and sneezing, but not between that expression level and nasal blockage or peak nasal inspiratory flow (PNIF). This correlation disappears with steroid treatment or after allergen provocation, although the expression at baseline seems to predict PNIF scores after provocation.. Our data not only reveals IL-10 expression by human nasal epithelial cells, but also suggests that nasal epithelial IL-10 regulates allergic symptoms. Targeting the regulation mechanisms affecting IL-10 or targeting the regulation mechanism affected by IL-10 could constitute new options for the treatment of allergic disease.

Topics: Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Antigens, Dermatophagoides; Female; Fluticasone; Humans; Interleukin-10; Male; Middle Aged; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Perennial

Fluticasone furoate is a novel-enhanced affinity glucocorticoid and its long-term safety must be assessed. This study was designed to assess the safety and tolerability of 12-month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR).. In this randomized, double-blind, placebo-controlled, parallel-group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 microg (n = 605) or vehicle placebo nasal spray (n = 201) for 12 months, following a 7- to 14-day screening period. Safety was assessed by monitoring adverse events (AEs), 24-h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples.. Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24-h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration.. Long-term (12-month) administration of fluticasone furoate 110 microg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Rhinitis, Allergic, Perennial

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.

Topics: Adult; Analysis of Variance; Androstadienes; Anti-Allergic Agents; Antihypertensive Agents; Biomarkers; Blood Pressure; C-Reactive Protein; Female; Fluticasone; Humans; Hypertension; Male; Middle Aged; Quality of Life; Rhinitis, Allergic, Perennial; Severity of Illness Index; Sodium Chloride; Surveys and Questionnaires; Terfenadine; Treatment Outcome

As a result of the all-year-round exposure to house dust mite (HDM), perennial rhinitis patients never have a clear symptom-free period. In this study, we investigated whether, despite these symptoms, we can still use nasal HDM provocations to study perennial allergic rhinitis and the effects of treatment.. In a parallel-group study, after 1 week treatment with either fluticasone propionate aqueous nasal spray (FPANS) or placebo, 20 patients, allergic to HDM, registered symptoms (nasal obstruction, rhinorrhoea, sneezing, pruritus and eye symptoms) using three different scoring methods [Lebel, categorical and visual analogue scale (VAS)] and peak nasal inspiratory flow (PNIF) after HDM provocations. Provocations were performed with 1000 biological units/ml and 24 h later with 10,000 biological units/ml of HDM. Before and after the provocations, nasal mucosa biopsies were taken for immunohistochemical staining to determine the number of eosinophils.. House dust mite provocations resulted in an increase in symptoms and a decrease in PNIF. Even at high-dose provocation, the FPANS group registered significantly lower symptoms than the placebo group for nasal blockage, sneezing, eye symptoms, and PNIF in both early and late phases. FPANS also suppressed rhinorrhoea during the late phase and the influx of eosinophils in the lamina propria.. Despite the high background of symptoms, allergic responses can be induced in this perennial rhinitis model. The VAS score seems most suited to detect these changes and the suppression of symptoms by 7 days of FPANS treatment. Epithelial eosinophilia at baseline was correlated positively with the severity of the reaction after the first provocation.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Animals; Dust; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Mites; Nasal Mucosa; Nasal Provocation Tests; Reproducibility of Results; Rhinitis, Allergic, Perennial; Time Factors

Topics: Acetates; Administration, Intranasal; Androstadienes; Circadian Rhythm; Cyclopropanes; Double-Blind Method; Fluticasone; Humans; Leukotriene Antagonists; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides

Data on intranasal corticosteroids suggest that individual product attributes may influence patient preference for therapy in allergic rhinitis. The study objective was to compare product sensory attributes and their impact upon patient preference for scent-free mometasone furoate nasal spray (MFNS) versus fluticasone propionate nasal spray (FPNS) in patients with symptomatic allergic rhinitis.. In a double-blind, crossover study, 100 patients were randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients rated the study drugs by completing an individual product sensory attributes questionnaire at the end of each period of drug administration. An overall sensory preference questionnaire was completed following crossover.. A significantly greater number of patients preferred MFNS to FPNS (p < 0.05). MFNS was superior for a number of individual sensory attributes based on mean patient ratings: significantly fewer patients perceived scent/odor (immediately and 2 minutes after drug administration; p < 0.001), taste (immediately after drug administration; p = 0.002), and after-taste (2 minutes after drug administration; p = 0.007) with MFNS compared with FPNS. Similarly, product sensory attribute preference data demonstrated that twice the number of patients preferred MFNS to FPNS for scent/odor (p = 0.0005), immediate taste (p = 0.005), and after-taste (p = 0.005). Fifty-four percent of patients said they would choose a prescription for MFNS compared with 33% for FPNS (p = 0.03). In addition, 47% of patients would be more likely to comply (use daily as directed) with MFNS compared with 25% with FPNS (p = 0.03).. Several individual sensory attributes of MFNS were rated significantly superior to FPNS. Overall, based on the tested sensory attributes, patients preferred MFNS to FPNS therapy for the treatment of allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Double-Blind Method; Fluticasone; Humans; Middle Aged; Mometasone Furoate; Patient Satisfaction; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients.. To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma.. A total of 863 patients (mean baseline FEV1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 microg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 microg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use.. FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (p < or = 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (p < or = 0.001) in all treatment groups, but improvements were comparable across the treatment groups.. In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

Topics: Acetates; Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Selection; Quinolines; Reproducibility of Results; Respiratory Distress Syndrome; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Sleep Wake Disorders; Sulfides; Treatment Outcome; Wakefulness

To investigate the effect of the nasal corticosteroid fluticasone propionate on the bioavailability and pharmacokinetics of single-dose intranasal hydromorphone hydrochloride in patients with allergic rhinitis.. Randomized, three-way, crossover pharmacokinetic study.. University clinical research unit.. Twelve patients with allergic rhinitis.. Hydromorphone hydrochloride 2.0 mg was administered by intravenous infusion (treatment A), intranasal spray without allergic rhinitis treatment (treatment B), and intranasal spray after 6 days of fluticasone propionate (treatment C). Blood samples were collected serially from 0-16 hours.. Pharmacokinetic parameters were determined by noncompartmental methods. An analysis of variance (ANOVA) model was used for statistical analysis. Mean (% coefficient of variation) absolute bioavailability of intranasal hydromorphone was 51.9% (28.2) and 46.9% (30.3) in patients with allergic rhinitis with and without treatment with fluticasone propionate, respectively. Mean maximum concentration (Cmax) values were 3.02 and 3.56 ng/ml, respectively. No statistical differences in Cmax and area under the concentration versus time curve were detected between intranasal treatments. Bioavailability values for both intranasal treatments were lower than those in healthy volunteers (57%). Median time to Cmax (Tmax) values were significantly different (p=0.02) for treatments B and C (15 and 30 min, respectively) using rank-transformed Tmax for ANOVA. Adverse effects were consistent with known effects of hydromorphone administered by other routes, with the exception of bad taste after intranasal administration.. Hydromorphone was rapidly absorbed after nasal administration, with maximum concentrations occurring for most subjects within 30 minutes. Allergic rhinitis may affect pain management strategies for intranasal hydromorphone, with a delay in onset of action for patients treated with fluticasone propionate.

Topics: Administration, Intranasal; Adult; Androstadienes; Area Under Curve; Biological Availability; Cross-Over Studies; Drug Therapy; Female; Fluticasone; Humans; Hydromorphone; Injections, Intravenous; Male; Middle Aged; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

To compare the safety and efficacy of fluticasone propionate aqueous nasal spray (FPANS) and oral ketotifen in children aged 2-4 years with perennial rhinitis. A randomized, multicentre, double-blind, double dummy, placebo-controlled study. Paediatric patients between the ages of 2-4 years with perennial rhinitis. Rhinitis symptoms score (parent-rated), clinical evaluation of symptoms (investigator-rated) and adverse event profiles during the treatment period. Patients treated with FPANS had a significant reduction in both the total night-time rhinitis symptom assessment for weeks 4-6 (p-value 0.036), and the total daytime rhinitis symptom score over the same period (p-value 0.049). Generally, except for nasal itching/rubbing over weeks 1-3, the patients taking FPANS had lower recorded symptom scores for all individual symptoms measured. Nasal blockage, in particular, was significantly reduced over the 4-6 week period (p-value 0.027). The overall investigator-rated clinical evaluation showed substantial improvement or improvement in nine of 12 of the children taking FPANS compared with four of 14 taking ketotifen. Finally, there were no reports of serious adverse events, the incidence of drug-related adverse events was low and there was no statistical difference between the groups. FPANS may be an appropriate treatment to control the symptoms of rhinitis in children between 2 and 4 years old.

Topics: Administration, Intranasal; Administration, Oral; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Child, Preschool; Double-Blind Method; Female; Fluticasone; Histamine H1 Antagonists; Humans; Ketotifen; Male; Rhinitis, Allergic, Perennial; Treatment Outcome

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

The purpose of this study was to evaluate the effects of triamcinolone acetonide (TAA) and fluticasone propionate (FP) aqueous nasal sprays on short-term lower-leg growth velocity and hypothalamic-pituitary-adrenal (HPA-axis function in pediatric subjects.. In this controlled, double-blinded (TAA) or single-blinded (FP), four-way crossover trial, 59 subjects (mean age: 7.2 years) were randomized to receive each of four 2-week treatments in random order: TAA nasal spray 110 microg, TAA nasal spray 220 microg, FP nasal spray 200 microg, and placebo, administered by a third party once daily with a 2-week washout period between treatments. Lower-leg growth velocity was measured by knemometry, and HPA-axis function was measured using 12-hour overnight urinary cortisol levels.. Forty-nine subjects completed all four treatments and were included in the analyses. Mean growth velocity (+/- standard error) was 0.46 (+/- 0.06) mm/week for placebo, 0.37 (+/- 0.06) and 0.31 (+/- 0.06) mm/week for TAA nasal spray 110 and 220 microg, respectively, and 0.37 (+/- 0.06) mm/week for FP nasal spray. The treatment effect on mean growth velocity compared with placebo was -19.6% with TAA 110 microg, -32.6% with TAA 220 microg, and -21.7% with FP; none of these effects was considered statistically or clinically significant according to predefined criteria. No significant differences in changes in urine cortisol/creatinine ratios were observed between TAA 110 microg or 220 microg and placebo (4.38, 3.60, and -0.67, respectively, P > or = 0.157). In contrast, the change in mean urine cortisol/creatinine ratio values for FP (-3.59) were significantly lower compared with TAA 220 microg (P = 0.033) and placebo (P = 0.003). Knemometry exhibited less time-dependent variability than overnight urinary cortisol measurements.. Neither TAA nor FP had a clinically significant effect on lower-leg growth velocity. In contrast to FP, TAA nasal spray did not significantly affect HPA-axis function when used over a 2-week interval.

Topics: Administration, Intranasal; Androstadienes; Bone Development; Child; Child Welfare; Child, Preschool; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Observer Variation; Pennsylvania; Pituitary-Adrenal System; Rhinitis, Allergic, Perennial; Single-Blind Method; Time Factors; Treatment Outcome; Triamcinolone Acetonide

Fluticasone propionate aqueous nasal spray (FP) at the highest recommended doses does not affect hypothalamic-pituitary-adrenal (HPA) axis function in adults or older children, but its potential effects in children younger than 4 years have not been previously studied. This randomized, double-blind, placebo-controlled study evaluated the effects of FP on HPA axis function measured by 12-hour urinary-free cortisol levels in children 2 to 3 years of age.. Patients ages 2 to 3 years with symptoms of allergic rhinitis were administered FP 200 microg/day (FP200 QD) or vehicle placebo for 6 weeks.. The FP200 QD group (n = 33) was equivalent to the placebo group (n = 32) in mean change from baseline in the primary safety measure of 12-hour creatinine-corrected urinary-free cortisol concentration (geometric mean difference [standard error; SE] for placebo-FP200 QD = 0.96 [1.20]; 95% confidence interval 0.66, 1.39) at the end of the treatment period. The adjusted geometric mean change from baseline value was 0.98 for FP200 QD (SE = 1.14) and 0.94 for placebo (SE = 1.15); a value of 1.0 reflects no change from baseline. Cough and fever were the most common adverse events reported in either group.. FP200 QD was equivalent to placebo with respect to effects on HPA axis function measured by 12-hour urinary-free cortisol in 2- and 3-year-old patients. FP200 QD was well-tolerated in these very young children with allergic rhinitis.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Chronic rhinosinusitis is frequently associated with asthma. A Th2 cytokine pattern has been recently reported in chronic rhinosinusitis in asthmatic children.. To evaluate the effects of treating concomitant chronic rhinosinusitis on respiratory symptoms and function and immunopathological parameters in asthmatic children.. Eighteen children with moderate asthma (age range, 5 to 12 years) poorly controlled by high doses of inhaled corticosteroids and chronic rhinosinusitis were evaluated for symptoms, spirometry, and inflammation at baseline, after treatment, and 1 month after suspension of treatment. All of the children were treated with a combination of amoxicillin and clavulanate (20 mg/kg twice daily) and fluticasone propionate aqueous nasal spray (100 microg/d) for 14 days. A short course of oral corticosteroids was also prescribed (deflazacort, 1 mg/kg daily for 2 days, 0.5 mg/kg daily for 4 days, and 0.25 mg/kg daily for 4 days). Rhinosinusal lavage for cytokine measurements and a nasal scraping for cytologic analysis were performed in all patients before and after medical treatment.. A negative endoscopy result was demonstrated in 15 children after treatment. Symptoms and respiratory function significantly improved after treatment and 1 month later; 8 children had intermittent asthma and 10 had mild asthma. A significant reduction of inflammatory cell numbers was detected in all asthmatic children. Interleukin 4 levels significantly decreased (P < 0.001), whereas interferon-y levels increased (P < 0.001).. Treatment of chronic rhinosinusitis is able to improve symptoms and respiratory function in asthmatic children, reducing inflammatory cells and reversing the cytokine pattern from a Th2 toward a Th1 profile.

Topics: Amoxicillin-Potassium Clavulanate Combination; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Drug Therapy, Combination; Endoscopy; Female; Fluticasone; Forced Expiratory Volume; Humans; Interferon-gamma; Interleukin-4; Male; Neutrophils; Pregnenediones; Rhinitis, Allergic, Perennial; Sinusitis

Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens.. These 2 studies compared patients' perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS).. In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, 1-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study 2, 100-microg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any).. A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in both studies), and a wet feel in both the nose and throat (study 1, P < 0.004; study 2, P < 0.002) with BANS than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P < 0.001; study 2, P < 0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant).. On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Budesonide; Cross-Over Studies; Female; Fluticasone; Humans; Male; Middle Aged; Pharmaceutical Solutions; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires

Intranasal corticosteroid preparations can relieve symptoms of allergic rhinitis. Different aqueous corticosteroid forms have been developed for intranasal use. The objectives of this study were to compare efficacy and safety between fluticasone propionate and budesonide in the treatment for patients with allergic rhinitis.. The study was conducted in a prospective and randomized manner; a total of 24 adult patients were enrolled. All patients received MAST allergen test at entry and again at 2 months after treatments. Fourteen patients received fluticasone propionate 200 microg once daily, and 10 patients received budesonide 200 microg twice daily. To investigate the efficacy of fluticasone propionate and budesonide, a subjective scoring system was designed to evaluate the symptom improvement of patients. Adverse events were recorded on a diary card then were analyzed. Mann-Whitney U test and Kruskal-Wallis 1-way analysis of variance were used for statistical analysis.. Analysis on patient-based symptom scores revealed that both fluticasone propionate and budesonide were equally efficacious in improving the symptoms of nasal blockage, sneezing, nasal itching, and watery rhinorrhea. There were no significant side effects reported for both groups during this follow-up period. However, analysis showed that the fluticasone propionate group demonstrated significantly greater improvement in some MAST allergen tests (Candida, mite, house dust; P < 0.05).. Clinically, fluticasone propionate 200 microg once daily was efficacious as budesonide 200 microg twice daily in the relief of allergic rhinitis symptoms. However, fluticasone propionate can achieve greater immunologic improvement. Both preparations showed no evidence of short-term side effects.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Budesonide; Drug Administration Schedule; Female; Fluticasone; Humans; Immunoglobulin E; Lectins, C-Type; Male; Membrane Glycoproteins; Prospective Studies; Receptors, Immunologic; Rhinitis, Allergic, Perennial; Trans-Activators

One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for the latter purpose.. This study compared the efficacy of combined use of fluticasone and olopatadine with combined use of fluticasone and fexofenadine in the treatment of the signs and symptoms of allergic rhinoconjunctivitis.. This 2-site, randomized, double-masked, placebo-controlled, parallel-group study employed the conjunctival allergen challenge (CAC) model, a standardized method of inducing ocular and nasal signs and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC to determine the dose of allergen required to elicit a positive reaction. The allergen dose was confirmed at visit 2, and, according to a randomization schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill; fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo pill, and tear substitute. CAC took place at visit 3, after patients had used the assigned medications for 2 weeks. Study medication was instilled 2 hours before CAC, after which allergic signs and symptoms were graded on standardized scales. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms.. Eighty subjects completed the study: 30 received fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo. Women constituted 63.8% of the study population and men 36.3%; 91.3% were white, 3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of fluticasone and olopatadine produced significantly greater improvements in ocular itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine (P < 0.05). There were no significant differences in redness scores between groups; however, concomitant use of fluticasone and olopatadine produced significantly greater improvements in redness at 2 time points in each of the 3 vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and fluticasone and fexofenadine produced significantly greater improvement in redness at 1 time point in I vessel bed compared with placebo (both comparisons, P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy scores.. In this study, concomitant use of the topical agents fluticasone and olopatadine was more effective than concomitant use of fluticasone plus fexofenadine for overall treatment of the signs and symptoms of induced allergic rhinoconjunctivitis.

Topics: Administration, Intranasal; Administration, Topical; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Conjunctivitis, Allergic; Dibenzoxepins; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Histamine H1 Antagonists; Humans; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Rhinitis, Allergic, Perennial; Terfenadine; Treatment Outcome

Although they have comparable safety and efficacy profiles, different intranasal corticosteroids possess different sensory/chemical properties that can be easily differentiated by patients, and which may influence their preference and compliance.. We sought to compare patient assessments of sensory attributes of three intranasal corticosteroid sprays: triamcinolone acetonide aqueous (TAA), fluticasone propionate (FP), and mometasone furoate (MF).. In a multicenter, randomized, double-blind, crossover study, 95 patients with allergic rhinitis rated 14 sensory items (100-point scales), product preference, and likelihood of compliance with treatment.. Immediately after administration, compared with MF, TAA was rated as having significantly better comfort during administration, less irritation, less odor strength, preferred odor, more moistness of nose/throat, milder taste (all P < or = 0.001), and preferred taste (P < or = 0.01). Compared with FP, TAA was rated as having significantly less odor strength, preferred odor (both P < or = 0.001), more moistness of nose/throat (P < or = 0.01), and milder taste (P < or = 0.05). Two minutes after application, TAA was rated as having less aftertaste than FP (P < or = 0.01) or MF (P < or = 0.001), and produced significantly less irritation (FP P < or = 0.05; MF P < or = 0.01). Of patients, 54.7% said they would prefer a prescription of TAA over one for MF (24.2%; P = 0.001) or FP (21.1%; P = 0.001). More patients indicated that they would be more compliant with treatment if given the TAA prescription (67.4%) than if given a prescription with FP (54.7%) or MF (49.5%).. Several of the TAA sensory attributes were preferred over those of MF and FP. Patient preference may play a role in enhancing treatment compliance. Such findings indicate that TAA nasal spray may be a better choice than MF or FP in the treatment of seasonal and perennial allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Patient Satisfaction; Perception; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Triamcinolone Acetonide

To evaluate whether 1 year of continuous treatment with intranasal fluticasone propionate would lead to atrophy in the nasal mucosa compared with an active control, oral terfenadine.. Prospective, randomized, multicenter, open-label, parallel-group study.. Two tertiary care academic institutions.. Seventy-five subjects older than 18 years with perennial allergic rhinitis.. Patients received either fluticasone propionate aqueous nasal spray, 200 microg once daily, or terfenadine, 60 mg twice daily, for 1 year. Nasal biopsy specimens were obtained before and after 1 year of treatment and were evaluated for evidence of atrophy.. Epithelial and collagen layer thickness of the nasal mucosa as assessed by light microscopy and the presence and degree of edema, and regularity of collagen fibrils as assessed by electron microscopy. Analyses were performed without knowledge of subject identity or treatment assignment.. Neither fluticasone nor terfenadine treatment led to atrophy in the nasal mucosa by clinical or histologic observation. No significant changes from baseline were observed for any assessment of atrophy. In contrast to what would have been expected if atrophy were to occur, mean epithelial layer thickness in the fluticasone group significantly increased compared with terfenadine treatment (P = .03).. Treatment with intranasal fluticasone for 1 year increases the thickness of the nasal epithelium as compared with a year's treatment with terfenadine and does not lead to atrophy in the nasal mucosa. The increased thickness in the fluticasone treatment may represent repair from epithelial damage caused by chronic allergic inflammation.

Topics: Administration, Intranasal; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Atrophy; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Mucosa; Prospective Studies; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Terfenadine

Previous studies comparing the corticosteroids fluticasone propionate (FP) and budesonide (BUD) in both perennial and seasonal rhinitis have shown no consistent difference between treatments. However, the therapeutic outcomes may have been influenced by study design.. To compare the effect of FP aqueous nasal spray (ANS; 200 microg/day) with BUD reservoir powder device (RPD; 200 microg/day) on rhinitis symptoms, productivity loss and device preference in patients with perennial rhinitis.. After a 2-week run-in period, 440 patients were randomized to receive either FPANS, BUD RPD or matched placebo (ANS or RPD) for 8 weeks, followed by an open-label 4-week follow-up treatment with FPANS. Patients completed diary card visual analogue scores for nasal symptoms, and questionnaires on satisfaction with the treatment and preferred choice of device.. During weeks 1-4, the visual analogue total nasal symptom scores (VATNS) in the FPANS group were significantly lower than scores in the BUD RPD group (mean difference = -17.8; 95% CI = -34.4, -1.3; P = 0.036). FPANS also significantly reduced the VATNS compared with the ANS placebo at all time-points assessed (P < or = 0.005). BUD RPD did not significantly differ from the RPD placebo at weeks 5-8 (P = 0.167), or the ANS placebo at any time-point (P < or = 0.151). Over the 8-week treatment period FPANS was significantly more effective than BUD RPD at reducing sneezing (mean difference = -4.4; 95% CI = -8.6, -0.3; P = 0.036) and nasal itching (mean difference = -5.3; 95% CI = -9.9, -0.8; P = 0.022), and was significantly superior to the ANS placebo for all symptoms assessed at weeks 1-4 and 1-8 (P < 0.016). At the same time-points BUD RPD was no better at alleviating nasal itching than the RPD placebo (P < or = 0.306), and compared with the ANS placebo, significantly reduced only one symptom; nasal blockage (P < or = 0.016). After 8 weeks of treatment, patients preferred the ANS device to the RPD (P < 0.001), and at 12 weeks a significantly greater number of patients were satisfied with FPANS treatment compared with BUD RPD (P = 0.0019) or the respective placebos (P = 0.0001).. FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo-controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Budesonide; Child; Confidence Intervals; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Powders; Rhinitis, Allergic, Perennial; Therapeutic Equivalency; Treatment Outcome

An economic evaluation was performed analyzing direct medical costs in Canada for the treatment of perennial allergic rhinitis (PAR) with budesonide aqueous nasal spray and fluticasone propionate nasal spray. Three hundred fourteen patients with at least a 1-year history of PAR were randomized into a double-blind, parallel-group study of 6 weeks' duration. The treatments were daily doses of budesonide 256 microg, fluticasone propionate 200 microg, or placebo. Both active treatments produced significantly lower mean scores for overall nasal symptoms compared with placebo, and both were well tolerated. Budesonide was significantly more effective than fluticasone in reducing "blocked nose.". A retrospective cost-effectiveness analysis utilizing the clinical trial data was performed on the total costs of (1) budesonide-based and (2) fluticasone-based treatment strategies, including the relative importance of the drug costs in both strategies.. The average treatment cost per patient in Canada over 12 months in the budesonide group was CAD 389.85 which was 23.3% lower than in the fluticasone group, which was CAD 508.06, due to lower drug acquisition costs (for the year 1998).. Budesonide aqueous nasal spray was shown to be more cost-effective than fluticasone propionate nasal spray in the treatment of perennial allergic rhinitis. This result is valid in the province of Ontario, Canada and in many other settings with the same structure of relative prices. The result is mainly driven by a difference in drug cost.

Topics: Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Budesonide; Canada; Cost-Benefit Analysis; Double-Blind Method; Fluticasone; Health Care Costs; Humans; Retrospective Studies; Rhinitis, Allergic, Perennial

One hundred and ten patients with perennial allergic rhinitis, currently symptomatic, were treated with fluticasone proprionate nasal spray (Flixonase) in open, multicentre efficacy and safety study. The drug studied statistically significantly decreased all symptoms of the disease conjunctivitis included, in the first week of treatment in the patient's and doctor's assessment. The full effect of treatment was revealed in the third week. There was significant protective effect observed during two weeks after the cessation of treatment. Adverse events were mild and occurred in fifteen cases, in two cases could be due to the drug (< 2%).

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Perennial

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Budesonide; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Reproducibility of Results; Rhinitis, Allergic, Perennial; Single-Blind Method; Treatment Outcome

The effect of long-term topical nasal corticosteroid therapy on nasal inflammatory cells is unclear.. To investigate the long-term effect of fluticasone propionate aqueous nasal spray (FPANS) on nasal mucosal inflammatory cells and efficacy in a 1-year study in patients with perennial allergic rhinitis.. In a 1-year, double-blind, placebo-controlled study of duration we investigated the influence of a topical corticosteroid (FPANS), on Langerhans' cells (CD1a+ cells), T cells, mast cells, eosinophils and macrophages in nasal mucosa in 42 patients with perennial allergic rhinitis. Efficacy was evaluated by nasal symptom score.. The FPANS group experienced significantly less sneezing and nasal itching compared with the placebo group. The total symptom score in the FPANS group declined significantly in comparison with baseline (P = 0.007) and placebo group (P = 0.009). After 1 year of active treatment, a significant decrease was seen in the epithelium in numbers of Langerhans' cells, CD3+, CD4+, CD8+ cells, mast cells and eosinophils. In the lamina propria, there was a significant decrease in eosinophils.. These findings show that FPANS treatment results in a decrease of nasal inflammatory cells. Furthermore, the efficacy of FPANS improves after prolonged treatment.

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Langerhans Cells; Macrophages; Male; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Perennial; T-Lymphocytes; Time Factors

In a 1-year, placebo-controlled, double-blind, randomized study the long-term effect of Fluticasone Propionate Aqueous Nasal Spray (FPANS) in 42 patients with a perennial allergic rhinitis was studied with regard to safety and efficacy. Twenty-nine patients completed the entire treatment period. After 1 year of treatment no deleterious changes consequent on therapy were observed in nasal mucosal biopsies. The appearance of the epithelial layer, the degree of cellular infiltration, the extent to which the sinusoids were dilated and the degree of tissue oedema improved or remained unchanged in 93% of the patients of the FPANS group, versus 75% of the placebo group, and worsened in 7% of the FPANS group versus 25% of the placebo group. Assessment of the changes in haematological, biochemical, urinary, plasma cortisol levels, and in the findings during nasal examination revealed no significant differences between the two treatment groups. After 1 year of treatment symptom scores for sneezing, nasal itching, and total symptom score were significantly better in the FPANS treated group (P < 0.05, P < 0.05, P < 0.01). An initial reduction in total symptom score was found after 4 weeks FPANS treatment with a further reduction after 8 months of FPANS treatment. These findings suggest that the maximum efficacy of topical intranasal steroids is reached after long-term treatment, and thus advocates longer usage before treatment is stopped because of presumed inefficacy.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Biopsy; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Nasal Mucosa; Rhinitis, Allergic, Perennial; Time Factors

Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis.. The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test.. In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol.. There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations.. These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis.. The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray.. This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment).. Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P =.03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P =. 009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P =.01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient.. Once daily budesonide aqueous nasal spray, 256 microgram, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 microgram, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Allergic Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Rhinitis, Allergic, Perennial

Acoustic rhinometry (AR) was used for objective measurements of nasal cavity dimensions in conjunction with a 100-mm horizontal visual analogue scale (VAS) for simultaneous subjective assessments of nasal sensations of airflow. Studies were conducted on 45 patients with perennial allergic rhinitis before, during and after a 2-week period of treatment with oral emedastine difumarate, azelastine hydrochloride, and xiao qing long tang (a homeopathic decongestant), as well as intranasal fluticasone propionate aqueous nasal spray. During the treatment period, there was a significant increase in the right and left minimum cross-sectional areas (MCA) of the nose and/or nasal cavity volumes (NCV) in all groups. The average increase in MCA ranged from 21-39% after 1 week of treatment and 16-39% after 2 weeks, whereas that in the NCV ranged from 16-24% and 19-24%, respectively. Post-treatment measurements were not significantly different from the corresponding pre-treatment ones. These findings were in close agreement with that obtained with VAS, demonstrating that AR can be used to validate the application of VAS in the evaluation of nasal airflow during medical therapy.

Topics: Acoustics; Administration, Intranasal; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Benzimidazoles; Evaluation Studies as Topic; Female; Fluticasone; Follow-Up Studies; Histamine H1 Antagonists; Homeopathy; Humans; Imidazoles; Male; Middle Aged; Naphazoline; Nasal Cavity; Nasal Decongestants; Nasal Obstruction; Nose; Phthalazines; Pulmonary Ventilation; Reproducibility of Results; Rhinitis, Allergic, Perennial

The reduction of symptoms due to treatment with corticosteroids varies among patients with perennial rhinitis. Most patients will respond but a few patients respond less to these drugs.. To investigate the association in reduction of symptoms due to glucocorticoids and glucocorticoid receptor characteristics in patients with perennial allergic rhinitis, in vitro glucocorticoid receptor binding studies were performed with peripheral blood mononuclear cells using dexamethasone and in vitro production of mediators were measured.. During a double-blind placebo-controlled crossover study, 200 micrograms fluticasone propionate aqueous nasal spray (in the active treatment period) and placebo (in the placebo treatment period) were administered twice daily for 2 weeks to 22 patients allergic to house dust mite. At the end of both treatment periods symptoms were scored after allergen provocation (100, 1000, 10000 BU/mL) and during the 9.5 hours after this challenge. Receptor binding studies with dexamethasone were performed with peripheral blood mononuclear cells. Leukotriene B4 produced by monocytes in vitro and soluble interleukin-2 receptor released by lymphocytes in vitro and cortisol levels in plasma were determined.. No significant partial correlations of the number of the peripheral blood mononuclear cell glucocorticoid receptors (6821 +/- 5669 binding sites per cell) and the affinity (Kd: 16.5 +/- 13.51 nmol/L) for the glucocorticoid receptors with the symptom score (placebo: 4.3 +/- 2.45 pts; fluticasone: 2.4 +/- 1.55 pts) after active treatment were found. Also no significant partial correlations of the levels of leukotriene B4 (45.6 +/- 105.3 ng/10(6) cells) produced by monocytes in vitro, soluble interleukin-2 receptor (734 +/- 237 ng/10(6) cells) released by lymphocytes in vitro and cortisol levels (571 +/- 236 ng/mL) in plasma with the symptom score after active treatment were found.. The reduction of symptoms due to topical fluticasone propionate in patients with rhinitis and allergy to house dust mite is not correlated with the characteristics of the glucocorticoid receptor.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Leukocytes, Mononuclear; Leukotriene B4; Male; Middle Aged; Receptors, Glucocorticoid; Receptors, Interleukin-2; Rhinitis, Allergic, Perennial; Solubility

Topical corticosteroid is now accepted as safe and most effective in controlling all symptoms of both allergic and nonallergic rhinitis. Fluticasone propionate aqueous nasal spray is a new once daily topical corticosteroid preparation.. To evaluate the efficacy and safety of fluticasone propionate in children 5 to 11 years of age with perennial allergic rhinitis.. A double-blind, placebo-controlled, parallel group of 127 recruited patients of whom 106 were evaluated. Treatment with once daily fluticasone propionate 100 micrograms or placebo for 4 weeks followed by a 2-week followup period. Fifty-three patients of each group were treated with fluticasone propionate or placebo by randomized assignment.. There was no statistical significance of the sex, mean age, weight, and height of the two groups. Patients treated with fluticasone propionate showed a significant decrease in total symptom scores rated by physicians at 2 weeks and 4 weeks, respectively (P < .01, P < .05). The rhinitis symptom scores in treatment group rated by patients (nasal blockage, sneezing, rhinorrhea) were significantly decreased at 2 weeks (P < .05, P < .01). Nasal symptoms as assessed by doctors (turbinate swelling, color of nasal mucosa, secretion, and postnasal drip) also decreased at 2 and 4 weeks, but were not statistically significant, except for the secretion at 2 weeks and postnasal drip at 4 weeks (P < .05). There was no evidence of effects on adrenal function by morning plasma cortisol concentration between the two groups.. Fluticasone propionate was safe and effective in children aged 5 to 11 years with perennial allergic rhinitis.

Topics: Administration, Inhalation; Aerosols; Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Nasal Mucosa; Rhinitis, Allergic, Perennial; Time Factors; Turbinates

Mometasone furoate (Nasonex), in a new once-daily aqueous nasal spray formulation, has been shown to be as effective and well-tolerated as twice-daily beclomethasone dipropionate aqueous nasal spray in treating symptoms of seasonal allergic rhinitis and perennial rhinitis.. To compare the effectiveness and tolerability of mometasone furoate to placebo and to fluticasone propionate aqueous nasal spray, all treatments administered once-daily, in patients with perennial rhinitis.. This was a 3-month, randomized, double-blind, double dummy, parallel group study in 550 patients, aged 12 to 77 years, at 25 centers in Canada, Latin America, and Europe. Patients allergic to at least one perennial allergen, with confirmed allergy history, skin test positivity, and moderate to severe symptomatology, were eligible to receive one of the following treatments, once daily in the morning: mometasone furoate 200 micrograms, fluticasone propionate 200 micrograms, or placebo. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment.. Four hundred fifty-nine patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < .01) more effective than placebo and was not statistically different from fluticasone propionate (percent reductions from baseline were 37, 39, and 22 for mometasone furoate, fluticasone propionate, and placebo, respectively). Generally, similar trends were seen for physician-evaluated total nasal symptoms, and patient-rated and physician-rated overall condition and response to therapy. Overall, mometasone furoate was at least as effective as fluticasone propionate at equivalent doses. There was no evidence of tachyphylaxis. All treatments were well tolerated.. Mometasone furoate and fluticasone propionate adequately controlled symptoms of perennial rhinitis and were well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents, Non-Steroidal; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial

Mometasone furoate (Nasonex), in a new once-daily aqueous nasal spray formulation, has been shown to be as effective and well-tolerated as twice-daily beclomethasone dipropionate aqueous nasal spray in treating symptoms of seasonal allergic rhinitis and perennial rhinitis.. To compare the effectiveness and tolerability of mometasone furoate to placebo and of fluticasone propionate aqueous nasal spray, all treatments administered once-daily, in patients with perennial rhinitis.. This was a 3-month, randomized, double-blind, double dummy, parallel group study in 550 patients, aged 12 to 77 years, at 25 centers in Canada, Latin America, and Europe. Patients allergic to at least one perennial allergen, with confirmed allergy history, skin test positivity, and moderate to severe symptomatology, were eligible to receive one of the following treatments, once daily in the morning: mometasone furoate 200 micrograms, fluticasone propionate 200 micrograms, or placebo. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment.. Four hundred fifty-nine patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < .01) more effective than placebo and was not statistically different from fluticasone propionate (percent reductions from baseline were 37, 39, and 22 for mometasone furoate, fluticasone propionate, and placebo, respectively). Generally, similar trends were seen for physician-evaluated total nasal symptoms, and patient-rated and physician-rated overall condition and response to therapy. Overall, mometasone furoate was at least as effective as fluticasone propionate at equivalent doses. There was no evidence of tachyphylaxis. All treatments were well tolerated.. Mometasone furoate and fluticasone propionate adequately controlled symptoms of perennial rhinitis and were well tolerated.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Placebos; Pregnadienediols; Rhinitis, Allergic, Perennial; Skin Tests; Treatment Failure

Intranasal corticosteroids have been shown to be more effective than oral antihistamines for the treatment of seasonal allergic rhinitis. However, there are some who question whether intranasally administered corticosteroids should be used due to potential systemic effects. Fluticasone propionate, a potent corticosteroid with high specificity for the glucocorticoid receptor, is available as an aqueous nasal spray for the treatment of allergic rhinitis. To determine whether the efficacy of fluticasone propionate aqueous nasal spray (FPANS) was due to direct topical effects on the nasal mucosa or to indirect systemic effects following absorption from the nasal mucosa or from the swallowed portion of an intranasal dose, FPANS 200 micrograms once daily was compared with oral fluticasone propionate 5 mg or 10 mg once daily or placebo for 2 weeks in patients with seasonal allergic rhinitis. These oral dosages were chosen to yield low but consistent plasma fluticasone propionate concentrations. Both clinician- and patient-rated scores for nasal obstruction, rhinorrhoea, sneezing, and nasal itching were significantly lower in the intranasal fluticasone propionate group compared with both oral fluticasone propionate groups. A separate placebo-controlled study was conducted in patients with perennial rhinitis to determine if administration of FPANS 200 micrograms once daily for 1 year was associated with adverse systemic effects. At the 1-year assessment, there were no significant effects on bone mineral density or on biochemical markers of bone turnover. Similarly, there was no evidence of posterior subcapsular cataracts nor of glaucoma. Furthermore, there were no significant effects on hypothalamic-pituitary adrenal axis function as assessed by plasma cortisol and 24-h urinary cortisol response to the 6-h cosyntropin stimulation test. These data confirm that the efficacy of FPANS for the treatment of allergic rhinitis results from direct topical effects, thus reducing the likelihood of adverse systemic effects.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Double-Blind Method; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Immune System; Male; Nasal Mucosa; Pituitary-Adrenal System; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

A total of 535 children aged 4-11 years with perennial rhinitis were recruited to two double-blind studies performed at 56 centres in eight European countries, Israel, and South Africa. One study compared the efficacy and tolerability of fluticasone propionate aqueous nasal spray (FPANS), at either 100 micrograms once daily (od) or 100 micrograms twice daily (bd), with beclomethasone dipropionate (BDPANS) 200 micrograms bd for 12 weeks in 120 children aged 6-11 years. The second study compared FPANS 100 micrograms od with FPANS 200 micrograms od and placebo for 4 weeks in 415 children aged 4-11 years. Efficacy was determined by means of patient assessments of nasal symptoms of perennial rhinitis and by investigator assessments of symptoms and nasal condition. The symptoms of nasal blockage, on waking and during the day, sneezing, rhinorrhoea, and nasal itching were assessed by the investigator at clinic visits and by the completion of a patient daily diary card. Safety was assessed by collection of adverse event information, routine haematology and biochemistry testing, and monitoring plasma cortisol levels. FPANS demonstrated good control of symptoms at each dose regimen, which was equivalent or superior to BDPANS and superior to placebo. There was no difference between the dose regimens of FPANS. FPANS was as well tolerated as placebo and BDPANS. It is concluded that FPANS 100 micrograms od is an effective and well-tolerated treatment for perennial rhinitis in children aged 4-11 years.

Topics: Aerosols; Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Rhinitis, Allergic, Perennial

The mechanism of action of topical intranasal steroids is obscure. To investigate this, we have studied the effects of a topical intranasal corticosteroid, fluticasone propionate on nasal airflow resistance (Rnaw), secretions, cytological smears and symptoms. Fluticasone propionate aqueous nasal spray was given to 11 patients with perennial allergic rhinitis in a double-blind, placebo-controlled study. On each day, patients were challenged with ascending doses of histamine. Rnaw, secretion volume, total protein, mucin, lysozyme and albumin were measured. Nasal smears were taken and sneezes counted. Diary card data were collected for both treatment periods. There was a significant, dose-related increase in Rnaw and sneezing on histamine challenge. A single dose of fluticasone had no effect on any parameter. After 4 weeks of treatment, resistance measurements were reduced (post-challenge g.m.2.8 cmH2O/l/s, Q1-Q3 1.6-4.8; placebo 4.2, 2.9-5.3: P < 0.0001) as were baseline secretion volumes (mean 2.4 ml/5 min, c.i.1.9-3.0; placebo 3.3, 2.8-3.8: P < 0.05). Eosinophil counts were suppressed (fluticasone 5.8%, c.i. 4.0-15.7; placebo 23.3%, 12.4-34.1: P < 0.05) and the composite symptom score reduced (P < 0.05). Fluticasone has long-term effects on the nasal response to histamine in perennial allergic rhinitis and part of this effect is likely to be vascular.

Topics: Administration, Topical; Adult; Aged; Airway Resistance; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Fluticasone; Histamine; Humans; Male; Middle Aged; Placebos; Rhinitis, Allergic, Perennial

Fluticasone propionate is a new potent, topically active corticosteroid with negligable oral bioavailability. Data on its comparative efficacy in perennial allergic and non-allergic rhinitis are limited.. To compare the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 micrograms once or twice daily with beclomethasone dipropionate aqueous nasal spray (BPD) 200 micrograms twice daily and placebo in patients with allergic and non-allergic perennial rhinitis.. The 12-week study had a multicentre, double-blind, randomized, parallel group design. Efficacy was assessed from symptom scores recorded on daily diary cards.. FPANS 200 micrograms once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non-allergic perennial rhinitis. There were few adverse events and no treatment-related abnormalities in laboratory measurements in either FPANS-treated group. Comparison between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied.. In the majority of patients FPANS 200 micrograms once daily in as effective as BDP 200 micrograms twice daily in the relief of perennial allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Rhinitis; Rhinitis, Allergic, Perennial

Symptoms of allergic rhinitis are associated with increased numbers of inflammatory cells in the nasal mucosa. The effects of fluticasone propionate on the nasal mucosal cells of patients with symptomatic allergic rhinitis were evaluated in seven multicentre, double-blind, parallel-group, placebo-controlled, randomised studies. In three seasonal allergic rhinitis studies, significantly more patients receiving fluticasone propionate had a decrease in nasal eosinophils following treatment compared with patients receiving placebo. Similarly, more patients receiving fluticasone propionate had a decrease in nasal basophilic cells, but differences from placebo were not significant in all studies. Nearly identical results were observed in two 24-week perennial allergic rhinitis studies: significantly more patients receiving fluticasone propionate or beclomethasone dipropionate had a decrease in nasal eosinophils compared with patients receiving placebo. Furthermore, a higher percentage of patients receiving corticosteroids also had a decrease in the number of basophilic cells. In two separate seasonal allergic rhinitis studies, significantly more patients receiving fluticasone propionate had a decrease in nasal eosinophils compared with patients receiving terfenadine or astemizole, respectively. The decrease in nasal basophilic cells was also significantly greater with fluticasone propionate compared with astemizole. Inhibition of mediator release from eosinophilic and basophilic cells has also been demonstrated in patients receiving fluticasone propionate compared with patients receiving antihistamines. The results of these studies suggest that the therapeutic benefits of fluticasone propionate aqueous nasal spray in the treatment of seasonal and perennial allergic rhinitis may be related to its ability to reduce nasal mucosal inflammatory cells and to inhibit local mediator activity.

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Nasal Mucosa; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans' cells and T-cells play an important role. Langerhans' cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T-cells by the IgE-positive Langerhans' cells. The T-cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T-cells is not usually influenced by corticosteroid treatment; however, the function of the T-cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans' cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T-cell stimulation may result in a reduction of the reactions that are dependent on T-cell-derived mediators.

Topics: Administration, Topical; Aerosols; Androstadienes; Anti-Inflammatory Agents; Antigen-Presenting Cells; Double-Blind Method; Eosinophils; Fluticasone; Glucocorticoids; Humans; Inflammation; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Perennial; T-Lymphocytes

The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined.. Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house dust mite. In a double blind placebo controlled crossover study fluticasone propionate 200 micrograms aqueous nasal spray was administered twice daily for two weeks. In response to provocation with house dust mite extract (after four basal nasal lavages) nasal lavages were performed every hour for 9.5 hours by washing the nose with saline. In addition, a similar lavage protocol was performed in healthy volunteers with or without challenge with phosphate buffered saline.. Nitric oxide is present in nasal lavage fluid in detectable amounts (range 10-50 microM), the level gradually increasing with time in both patients and controls after a decrease during the four basal lavages. Treatment with fluticasone propionate aqueous nasal spray did not affect initial basal production of nitric oxide nor production following provocation with house dust mite extract.. Production of nitric oxide in nasal mucosa determined in sequential nasal washings is not affected by therapeutic doses of intranasal steroids.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Animals; Anti-Inflammatory Agents; Cross-Over Studies; Double-Blind Method; Dust; Female; Fluticasone; Glucocorticoids; Humans; Male; Mites; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Nitric Oxide; Rhinitis, Allergic, Perennial

The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double-blind, placebo-controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a+ cells), HLA-DR+ cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CD1a+ cells and HLA-DR+ cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Antigens, CD; Double-Blind Method; Female; Fluticasone; Glucocorticoids; HLA-DR Antigens; Humans; Langerhans Cells; Male; Nasal Mucosa; Placebos; Rhinitis, Allergic, Perennial; T-Lymphocytes

There is circumstantial evidence that the incidence of allergic rhinitis is becoming increasingly common. There may also be a need for more potent drugs with minimal local and systemic side effects. This study has compared the efficacy and safety of budesonide delivered as nasal dry powder with fluticasone propionate aqueous nasal spray in the treatment of perennial allergic rhinitis. Ninety-eight patients participated in a randomized, parallel group and partly blinded study. Treatment consisted of budesonide dry powder (Rhinocort Turbuhaler) at once daily doses of 200 micrograms (n = 24) or 400 micrograms (n = 22), fluticasone propionate (200 micrograms) once daily (n = 25), and placebo for budesonide dry powder (n = 27). A six-week treatment period was preceded by a two-week baseline period without treatment. Efficacy was assessed by daily subjective scoring of nasal symptoms. Safety was assessed by rhinoscopy, analysis of urine cortisol, and questioning of adverse events. All active treatments were significantly superior to placebo in controlling nasal symptoms. No significant differences in efficacy were found between the two budesonide regimens and fluticasone propionate. Adverse events were few and minor, and non-significantly distributed between treatments. In conclusion, this study shows that budesonide dry powder administered from Turbuhaler (200 or 400 micrograms) and fluticasone propionate aqueous spray (200 micrograms) administered in once daily doses, are effective and safe treatments of perennial allergic rhinitis. These novel treatments may enhance the current available alternatives in clinical practice.

Topics: Administration, Topical; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Budesonide; Female; Fluticasone; Glucocorticoids; Humans; Male; Powders; Pregnenediones; Rhinitis, Allergic, Perennial; Time Factors

Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli.. To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity.. Twenty-four rhinitis patients allergic to house dust mite (HDM), participated in a double-blind, placebo-controlled crossover study. After 2 week's treatment with placebo or 200 micrograms FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreactivity was determined by histamine challenge 24 h later.. Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%, 69% and 63% after 100, 1000 and 10,000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU/mL (P = 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32% and sneezes with 41%.. FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.

Topics: Administration, Intranasal; Adult; Androstadienes; Animals; Anti-Inflammatory Agents; Antigens, Dermatophagoides; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Glycoproteins; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Male; Middle Aged; Mites; Nasal Mucosa; Rhinitis, Allergic, Perennial

The investigations were carried out on 13 children with seasonal rhinitis, and in 10 children with perennial rhinitis. The fluticasone propionate (Flixonase-Glaxo) was introduced in acute state of disease: one dose to each nostril (100 micrograms) for the patient 7-11 years old, and in the patients under 11 years old--two doses to each nostril (200 micrograms) in the morning, during 3 weeks. The clinical effects were established using score-system in 0-3 points scale which included essential symptoms like: itching, sneezing, nasal blockade, rhinorrhoea, mucosal oedema and eyes irritation. Very good and good effects of the treatment in patients with seasonal rhinitis in 93% of children was observed. In the group of patients with perennial rhinitis, very good and good results, was observed in 80% of children. Easy dosage, high efficacy, very nice smell and no side-effects make this medicine very usefull in the treatment of allergic rhinitis in children.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Child; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

Nasal cytograms of patients with allergic rhinitis contain increased numbers of eosinophils and basophilic cells. Neutrophils are also more numerous in cytograms of allergic persons. Topical intranasal corticosteroid therapy for allergic rhinitis has been shown to decrease the numbers of some inflammatory cell types. Fluticasone propionate aqueous nasal spray, a potent synthetic corticosteroid preparation, is effective therapy for seasonal and perennial allergic rhinitis.. Nasal mucosal scrapings were obtained with a Rhinoprobe (Apotex Scientific, Inc. Arlington, Texas) before and after therapy with fluticasone propionate aqueous nasal spray at several doses in patients with either seasonal allergic rhinitis (2 to 4 weeks' therapy) or perennial allergic rhinitis (24 weeks' therapy). More than 1000 paired nasal cytograms obtained from patients participating in five multicenter studies were evaluated.. The percentage of patients with nasal eosinophils (p < 0.01, most studies) and basophilic cells (p < 0.05, most studies) decreased significantly after treatment with fluticasone propionate compared with placebo-treated patients. Similar findings were observed with beclomethasone dipropionate in one study. The number of neutrophils remained relatively unchanged after treatment with the intranasal corticosteroids or placebo.. These findings suggest that the therapeutic benefits of topical intranasal fluticasone propionate and beclomethasone dipropionate for the therapy of seasonal and perennial allergic rhinitis are reflected by the decrease in inflammatory cells in the nasal mucosa.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Nasal Mucosa; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

The efficacy of intranasal fluticasone propionate 200 micrograms once daily or 100 micrograms twice daily in treating perennial allergic rhinitis was evaluated in a randomized, double-blind, placebo-controlled study of 24 weeks' duration in 365 patients. Clinician-rated and patient-rated total nasal symptom severity scores were improved within 1 week of treatment with either regimen of fluticasone propionate and improvement was maintained over the 24-week treatment period. Clinician-rated overall evaluation indicated a significantly better response in the two fluticasone propionate groups compared with the placebo group. All efficacy evaluations indicated no difference in response between the fluticasone propionate 200 micrograms once-daily and 100 micrograms twice-daily groups. Patients in both fluticasone propionate groups had significantly less nasal obstruction upon awakening than the placebo group at all assessment periods. Fewer patients in either fluticasone propionate group used antihistamine rescue medication compared with the placebo group. The percentage of patients with nasal eosinophils and basophils at the end of the 24-week treatment period was significantly lower in both fluticasone propionate groups compared with the placebo group. Safety evaluations indicated that intranasal fluticasone propionate was as safe as placebo when given as 200 micrograms once daily or 100 micrograms twice daily. The incidence of drug-related adverse events was similar among the fluticasone propionate and placebo groups except for the incidence of epistaxis and blood in nasal mucus which was somewhat higher in the fluticasone propionate twice-daily group. There was no changes in the opthalmic examinations to suggest corticosteriod-induced posterior subcapsular cataract formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Child; Double-Blind Method; Fluticasone; Humans; Hydrocortisone; Middle Aged; Rhinitis, Allergic, Perennial; Severity of Illness Index; Time Factors

Two hundred and fifty-one patients, aged 16 years and over, with perennial rhinitis were recruited to this multicentre, randomized, double-blind, parallel group study. One hundred and fifty-nine patients received fluticasone propionate (200 micrograms) aqueous nasal spray (FPANS) twice daily, and 83 patients received beclomethasone dipropionate (200 micrograms) aqueous nasal spray (BDPANS) twice daily; treatment randomization being 2:1, respectively, in order to increase the number of patients in the FPANS group as FPANS was the drug under study. After 1 year of treatment, nasal blockage (p = 0.002), nasal discharge (p = 0.002) and eye watering/irritation (p = 0.048) were significantly improved in patients treated with FPANS twice daily, compared to patients treated with BDPANS twice daily. The symptom grades for nasal itching (p = 0.052) were improved in the FPANS group, but just failed to attain statistical significance at the 5% level. The symptom grades for sneezing tended to be better for the FPANS group, but the difference was not statistically significant. Assessment of changes in the findings during nasal examination (rhinoscopy) and in haematological, biochemical and urinary parameters, and measurements of plasma cortisol levels during the one year of treatment with the study drugs, showed that there were no clinically significant differences between the two treatment groups and that the study drugs were equally well tolerated. This study indicates that long-term use of FPANS provides better relief than BDPANS for most of the symptoms of perennial rhinitis.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Double-Blind Method; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Perennial; Time Factors

Fluticasone propionate aqueous nasal spray, a new potent corticosteroid, is effective when given once or twice daily for seasonal allergic rhinitis.. Fluticasone propionate was compared with beclomethasone dipropionate in a multicenter double-blind, randomized, placebo-controlled, parallel-group study in 466 patients with perennial allergic rhinitis. Adults and adolescents (aged 12 to 71 years) with moderate to severe symptoms, nasal eosinophilia, and a positive skin test reaction (> or = 2+) to a perennial allergen received fluticasone propionate aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice daily, or placebo for 6 months.. Clinician- and patient-rated scores for nasal obstruction (including obstruction on awakening), rhinorrhea, sneezing, and nasal itching were reduced by the first visit at 7 days after initiation of active treatment and remained lower than those of patients receiving placebo throughout the 6-month treatment period. Nasal eosinophilia was reduced in significantly more patients receiving active treatment. The incidence of adverse events was similar in all four treatment groups except for blood in nasal mucus, which was reported by significantly more patients in the two twice-daily active treatment groups compared with the placebo group. There was no evidence of systemic effects of fluticasone propionate. There were no significant differences between fluticasone propionate given once or twice daily or beclomethasone dipropionate given twice daily for any efficacy or safety evaluation.. Fluticasone propionate aqueous nasal spray given once daily in the morning is safe and effective therapy for perennial allergic rhinitis and is as effective as twice daily dosing with fluticasone propionate or beclomethasone dipropionate.

Topics: Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Rhinitis, Allergic, Perennial

Topics: Administration, Intranasal; Adult; Airway Resistance; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Glucocorticoids; Humans; Male; Mucociliary Clearance; Rhinitis, Allergic, Perennial

MP 29-02, which contains fluticasone propionate and azelastine hydrochloride, is used as a topical nasal application for the treatment of seasonal and perennial allergic rhinitis. Although a multitude of data is available on the clinical symptom reduction and treatment safety of MP 29-02, the effect of MP 29-02 on ciliary beat frequency (CBF) has not been evaluated thus far.. MP 29-02-containing solution was applied at concentrations of 2.5, 5, 10, and 20% to 14 healthy subjects, and nasal ciliated epithelial cells were then visualized using a phase-contrast microscope. CBF was measured after the application of MP 29-02. For a comparison, fluticasone propionate was used. CBF measurements were then performed for 15 min at 22 °C. Ringer's solution was applied as a negative control.. MP 29-02 significantly reduced CBF at all the tested concentrations compared with that of the control group within the observation time. At a 2.5% concentration, MP 29-02 significantly reduced CBF from 6.81 Hz (SD ± 1.35 Hz) at baseline to 4.88 Hz (SD ± 1.52 Hz, p < 0.001) after 15 min. In contrast, for fluticasone propionate, a significant reduction was observed only with the 20% concentration after 5, 10, and 15 min.. MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.

Topics: Administration, Intranasal; Adult; Androstadienes; Drug Combinations; Epithelial Cells; Female; Fluticasone; Humans; In Vitro Techniques; Male; Middle Aged; Nasal Mucosa; Phthalazines; Rhinitis, Allergic, Perennial

The purpose of this study was to investigate the effect of MP-AzeFlu on olfaction and the interaction between severity of allergic rhinitis and olfactory improvement after therapy.. A prospective, multicenter, observational study was performed on 47 patients with persistent allergic rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and the proof of allergen sensitization from positive skin-prick tests, specific immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory function was assessed at baseline and at 1 and 3 months of therapy using the "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a visual analog scale (VAS) at each given time-point.. MP-AzeFlu was found to be associated with a significant improvement in TDI score, from 23.7 at baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of treatment. Furthermore, a highly significant improvement of symptoms over time (p < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be demonstrated. Most importantly, there was a highly significant interaction between the severity of allergic rhinitis and olfactory function (p < 0.001) and VAS (p < 0.001).. MP-AzeFlu is associated with olfactory improvement in persistent allergic rhinitis patients. Further, the modified ARIA severity classification is an indicator of patients' olfactory function. Moreover, assessment of olfaction seems to be a reliable indicator of the clinical success of antiallergic/antiinflammatory therapy.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Female; Fluticasone; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic, Perennial; Smell; Treatment Outcome; Young Adult

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Fluticasone; Humans; Phthalazines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Allergic rhinitis affects over 20% of the UK population. It can have a significant impact on quality of life and interferes with both attendance and performance at school and at work.1 Intranasal corticosteroids are widely recognised as the most effective symptomatic treatment available, but oral or intranasal new generation antihistamines are usually offered as first-line treatment for intermittent symptoms.1,2 Patients with moderate to severe allergic rhinitis may require a combination of drugs, and many patients only achieve limited control of their symptoms.3 Dymista is described as a novel intranasal formulation combining the antihistamine azelastine hydrochloride with the corticosteroid fluticasone propionate.3 It is licensed for the relief of symptoms of moderate to severe seasonal and perennial allergic rhinitis in adults and adolescents if monotherapy with either intranasal antihistamine or glucocorticoid is not considered sufficient.4 The manufacturer claims that compared with fluticasone or azelastine alone, Dymista is twice as effective (when placebo effect is excluded) in providing relief from both nasal and ocular symptoms, and leads to greater overall relief from nasal symptoms. It also claims that Dymista controls nasal symptoms up to 6 days faster than fluticasone.5 Here we consider the evidence for Dymista and whether it represents a significant advantage in the management of patients with allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Drug Combinations; Fluticasone; Humans; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Time Factors

Topics: Acetates; Adult; Aminophenols; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Cystic Fibrosis; Female; Fluticasone; Humans; Leukotriene Antagonists; Paranasal Sinus Diseases; Quinolines; Quinolones; Rhinitis, Allergic, Perennial; Sulfides; Treatment Outcome; Young Adult

Allergic rhinitis is a very common disease that causes high economic costs. Furthermore inadequate treatment can lead to bronchial asthma. Against this background, drugs for the treatment of allergic rhinitis should be evaluated from a comprehensive medical-economic perspective. The new combination of an antihistamine and a corticosteroid, introduced in the market in 2013, emerges as useful pharmaceutical alternative, both with regard to the medical outcome parameters as well as cost-effectiveness.

Topics: Absenteeism; Administration, Intranasal; Adolescent; Adult; Androstadienes; Asthma; Child; Child, Preschool; Cost-Benefit Analysis; Drug Combinations; Female; Fluticasone; Germany; Humans; Male; National Health Programs; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Socioeconomic Factors

An Afro-Caribbean girl showed localized hair depigmentation during treatment with inhaled fluticasone propionate. Although skin depigmentation is common after topical use of corticosteroids, hair depigmentation has never been reported with inhaled corticosteroids. The mechanisms underlying corticosteroid-induced skin depigmentation are not completely understood, but accepted hypotheses suggest a direct cytotoxic effect, changes in ground substance, vasoconstriction, mechanical effects of edema, or a dysregulation of melanogenesis.

Topics: Androstadienes; Animals; Anti-Allergic Agents; Asthma; Child, Preschool; Conjunctivitis; Edema; Female; Fluticasone; Hair Color; Hair Diseases; Humans; Pyroglyphidae; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; Vasoconstriction

We present two patients with allergic rhinitis who developed perioral dermatitis (PD) after initiating intranasal steroid spray. Both patients had been previously misdiagnosed as having contact or seborrheic dermatitis, and therefore inappropriately and unsuccessfully treated with topical steroids. Physicians should be aware of this potential side effect of intranasal steroids to avoid incorrect therapeutic measures. In the setting of nasal steroids use, PD probably is an under-reported and commonly misdiagnosed condition that should be thought when a patient treated with nasal steroids present with small erythematous papules, papulovesicles, and papulopustules occurring against a background of redness, beginning in the nasolabial areas and spreading rapidly to the perioral zone.

Topics: Administration, Intranasal; Adolescent; Androstadienes; Anti-Allergic Agents; Child; Dermatitis, Perioral; Female; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial

Topics: Administration, Inhalation; Androstadienes; Anti-Allergic Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Eye; Female; Fluticasone; Follow-Up Studies; Humans; Male; Nasal Cavity; Nasal Sprays; Retrospective Studies; Rhinitis, Allergic, Perennial; Severity of Illness Index; Treatment Outcome

Although systemic, topical, and periocular corticosteroid administration have long been associated with ocular side effects, there has been little evidence to suggest that long-term inhaled corticosteroids can cause ocular side effects. The aim of this study was to evaluate the effects of long term treatment inhaled fluticasone propionate spray usage the recommended dose on some ocular functions in pediatric patients with asthma.. The study group consisted of 266 prepubertal children with asthma who had used inhaled fluticasone propionate spray at 3-6 years intermittently. One hundred and sixty children who were newly diagnosed with asthma without any treatment made up the control group. Schirmer test results, central corneal thickness, visual acuity, intraocular pressure, cataract formation, keratometry and tear break-up time compared between study and control groups.. The ages of the 266 study patients (150 male) were between 7 and 11 years. The average age (±SEM) was 8.2±1.7 years, and the mean (±SEM) a daily dose of 323 μg (range 250-450 μg) inhaled fluticasone propionate spray, with 865.2±215 g total steroid use during treatment. Eye functions including cataract formation, corneal ectasia, ocular hypertension or glaucoma, and dry eye were not observed in any of the patients in the study group and were not correlated with total steroid dosage (t=0.150, p=0.384).. Our findings suggest that long-term intermittent treatment for 3-6 years with inhaled fluticasone propionate spray, as much as average 320 μg daily, in children with asthma seems to be safe for some eye functions.

Topics: Androstadienes; Asthma; Bronchodilator Agents; Case-Control Studies; Child; Female; Fluticasone; Humans; Intraocular Pressure; Male; Rhinitis, Allergic, Perennial; Tears; Time Factors; Visual Acuity

To investigate the dynamic process of the nasal mucosal remodeling, and the effect of the fluticasone propionate (FP) to remodeling, by establish animal model of allergic rhinitis (AR).. One hundred and twenty Sprague-Dawley (SD) rats were randomly divided into three groups: the normal Group A used as controls and experimental groups: Group B and C, each group had 40 rats. After the animal model were established successfully by OVA+ Al (OH)3 and disposed, then, the dynamic process of the nasal mucosal remodeling was observed, through HE staining and transmission electron microscopic section in special times.. The Group B, C nasal epithelium and cilia were not complete, eosinophil-based inflammatory cell infiltration, basement membrane thickening, collagen deposition, and a small amount of fibrosis could be found, but the structure of cells were not damaged. While those changes could not be observed in the Group A. The morphological changes of the nasal mucosa of Group B aggravated gradually under persistent allergen exposure, even stripped to the basement membrane in whole epithelial layers, cell and tissue structure were destroyed seriously. The morphological changes of nasal mucosa of Group C did not further increase, but still showed varying degrees of cilia arranged in uneven fashion, basement membrane thickening, collagen deposition and fibrous hyperplasia after treatment by FP.. Remodeling happens in the nasal mucosa, which would be aggravated, and even becomes irreversible if the allergen exposure continues persistently. The FP can relieve the clinical symptoms, slow down and even reverse the remodeling of AR. And it is ineffective when the changes become irreversible.

Topics: Androstadienes; Animals; Disease Models, Animal; Female; Fluticasone; Male; Nasal Mucosa; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic, Perennial

Intranasal corticosteroids (INS) are the first line treatment for allergic rhinitis (AR). To guide clinical decision-making, we created a therapeutic index (TIX) for INS reflecting efficacy and safety.. A Medline search (1966 to June 2009) was carried out to identify all placebo-controlled randomized trials, and observational reports for safety issues, with Dexamethasone, Budesonide (BUD), Fluticasone propionate (FP), Fluticasone furoate (FF), Flunisolide, Mometasone furoate (MF), Triamcinolone (TRIAM), and Beclomethasone dipropionate (BDP) as treatment for AR. Data on three efficacy (nasal symptoms, ocular symptoms, global assessment) and three safety outcomes (epistaxis, growth, systemic ocular effects) were extracted. Meta analyses were performed for each INS and outcome and results were categorised into scores by quartiles. Scores of the three efficacy and safety outcomes were summed up to create summation scores for efficacy (ES) and side effects (AES), respectively with a maximum of 9 points. The TIX was then defined as the ratio of ES and AES.. Data of 84 studies were extracted. Based on availability of data, a TIX was calculated for 6 substances. BUD showed the highest efficacy score followed by MF and TRIAM. The lowest scores for side effects were achieved by MF and TRIAM followed by FP. These findings resulted in TIX scores of 7 and 5 for MF and TRIAM, respectively, indicating a high efficacy and low potential of adverse events. Medium scores were reached by BUD and FP and lower scores by BDP and FF.. Although safety and efficacy is proven for all available INS by multiple studies, the systematic aggregation and analysis of data allows for a differentiated summary on clinically important features.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Treatment Outcome; Triamcinolone

Intranasal corticosteroids (INCSs) seem to be the best medication available to control and eliminate symptoms of allergic rhinitis. However, the amounts of nasal steroids prescribed and used were not directly proportional to the number of allergic rhinitis cases in Turkey. Herein, we aimed to clarify the unexpectedly low prescription and use of INCSs in Turkey by checking the outlook of patients' and physicians' perspectives. The patients' perspective on oral and nasal steroids was evaluated with a custom-designed questionnaire drawn up specifically for this preliminary study. The physicians' perspective on prescribing nasal steroids was evaluated with the data obtained from the IMS Health Turkey reports. The findings we obtained in this survey by analyzing data from the self-administered questionnaires showed that among these young people, oral and nasal steroids were on the whole well-known drugs. Hence, even though steroids in general are well-known drugs, the young people we surveyed mainly remained uninformed about their safety. The incidence of using nasal steroids if prescribed is higher than the one with oral steroids; that may be due to the lack of knowledge about nasal steroids. The analysis of the IMS Health Turkey data for nasal steroid prescriptions between 2005 and 2008 shows that the market share has increased steadily. The role of INCSs in the treatment of allergic rhinitis is increasingly being recognized as an appropriate and effective treatment option. However, patients' and parents' concerns over the safety of INCS therapy have frequently resulted in their being positioned as a second-line treatment choice. Physicians need to be aware that patients may have a significant information gap. Instructing the family and caregivers about the correct use of INCS therapy is an important part of treatment.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Attitude of Health Personnel; Budesonide; Drug Prescriptions; Female; Fluticasone; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Surveys and Questionnaires; Triamcinolone; Young Adult

To clarify the role of glucocorticoid receptor-beta in resistance to glucocorticoid therapy for allergic rhinitis, we studied 37 tissue samples from 20 patients with severe allergic rhinitis, and samples from age-matched controls.. Patients were treated with intranasal fluticasone for 6 months and inferior turbinectomy was performed for patients with poor response to glucocorticoid treatment. The expression of glucocorticoid receptor-alpha (GR-alpha), glucocorticoid receptor-beta (GR-beta), and nuclear factor-kappaB (NF-kappaB) in nasal mucosa was studied immunohistochemically.. GR-alpha and NF-kappaB were expressed to a similar extent in patients and controls, but GR-beta was expressed significantly more in patients, resulting in an increased GR-beta/GR-alpha ratio.. Our findings suggest that GR-beta plays an important role in resistance to glucocorticoid therapy for allergic rhinitis, and its expression might be used as an additional parameter indicating steroid resistance in allergic rhinitis.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Drug Resistance; Female; Fluticasone; Humans; Male; Microscopy, Fluorescence; Nasal Mucosa; NF-kappa B; Receptors, Glucocorticoid; Reference Values; Rhinitis, Allergic, Perennial; Young Adult

Recent guidelines reveal that allergic rhinitis impairs quality of life. Neuropeptides play a central role in allergy-related nasal inflammation. The objective of this study was to analyze the release of neuropeptides (substance P, neurokinin A, and vasoactive intestinal peptide) in nasal lavage and their modification by intranasal fluticasone propionate as an established therapy in patients with allergic rhinitis.. Eleven patients with proven allergic rhinitis induced by house dust mite were challenged before and after administration of fluticasone propionate nasal spray. Nasal lavage samples were collected after allergen challenge, and neuropeptides were measured using enzyme-linked immunosorbent assay. Values for histamine, protein, and human serum albumin were also recorded. Eight healthy individuals were included as nonatopic controls.. The neuropeptides investigated were detectable in nasal lavage fluid in both patients and controls. Treatment with fluticasone propionate significantly decreased clinical response to allergen challenge (P < .01) compared with the controls and led to a decrease in values for substance P, neurokinin A, vasoactive intestinal peptide, histamine release, human serum albumin, and total protein after allergen challenge (P < .01).. The demonstration of proinflammatory neuropeptides in NAL and suppression of their release after allergen challenge caused by a topical corticosteroid suggest a role for neuropeptides in allergic inflammation. Diminished release of neuropeptides induced b fluticasone propionate was accompanied by an improvement in the clinical symptoms of patients with persistent allergic rhinitis.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Antigens, Dermatophagoides; Female; Fluticasone; Histamine; Humans; Male; Middle Aged; Nasal Lavage Fluid; Neurokinin A; Rhinitis, Allergic, Perennial; Serum Albumin; Statistics, Nonparametric; Substance P; Vasoactive Intestinal Peptide; Young Adult

Persistent allergic rhinitis (AR) and asthma constitute a common comorbidity. Combined treatment is recommended by prescribing intranasal plus oral inhaled corticosteroids. This study was carried out to assess the efficacy of an alternative regimen to treat this condition. All recruited patients suffered from persistent AR and asthma. Diagnosis and classification of AR and asthma were based on international guidelines. The experimental group received fluticasone propionate (FP), 500microg/day during six weeks, inhaled exclusively through the nose using a valved large volume spacer attached to a face mask. The comparison group also received the same dose of orally inhaled FP, during the same time period, plus intranasal aqueous fluticasone, 200microg/day. There were no statistical differences between both groups regarding AR and asthma severity, clinical scores, acoustic rhinometry, lung function, and FeNO upon admission and during the follow up period. Intragroup analysis demonstrated a significant improvement for allergic rhinitis and asthma scores as well as for FeNO from admission to the sixth week (p<0.01) in both groups. Results suggest that exclusive nasally inhaled fluticasone propionate should be considered as an alternative step in the management of patients suffering from AR and asthma comorbidity.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Androstadienes; Asthma; Child; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Perennial; Treatment Outcome; Young Adult

To investigate the effects of fluticasone on expression of basic fibroblast growth factor and mRNA in allergic rhinitis rats.. Ninety Sprague-Dawley rats were randomly divided into three groups(n = 30 for each), including AR group, control group and fluticasone treatment group. In this experiment, the rat model of AR was established by the ovalbumin challenge methods. The expression of the protein of basic fibroblast growth factor and mRNA were detected with immunohistochemistry methods and in RT-PCR methods.. The protein and mRNA expression of basic fibroblast growth factor in nasal tissue was significantly higher in the AR group than that in control group (P < 0.01), and it was much lower in the treatment group than that in the AR group (P < 0.01), but still higher than that in the control group (P < 0.01). The epithelial cell was the chief expression cell.. The basic fibroblast growth factor participates in the pathogenesis of AR, and inhaled fluticasone can significantly inhabit the expression of the protein and mRNA of basic fibroblast growth factor in the chronic stage of AR, thus preventing the airway remodeling.

Topics: Androstadienes; Animals; Female; Fibroblast Growth Factor 2; Fluticasone; Male; Nasal Mucosa; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic, Perennial; RNA, Messenger

To investigate the expression and distribution of aquaporin 5 (AQP5) in allergic rhinitis (AR) treated by fluticasone propionate and levocabastine.. Forty Wistar rats were divided randomly into AR (n=30) and control groups (n=10). After AR models were established, the AR rats were divided evenly into F group, L group and AR control group. Three groups were treated respectively for 28 days, then the expression of AQP5 in nasal mucous membrane were detected by immunohistochemistry assay.. The distribution of AQP5 was consistent in all groups. The expression of AQP5 in F group was significantly different from L group and AR group (P<0.05), while there was no significant difference between that of AR group and L group (P>0.05). The expression of AQP5 in L group was significantly different from that in control group (P<0.05).. High expressions of AQP5 in rat with AR indicated the positive correlation between AQP5 and AR. AQP5 might be one of pathological factors of AR concerned with glands excessive secretion and tissue edema. Glucocorticoid can down-regulate the expression of AQP5, but H1-receptor antagonist can not reduce the expression of AQP5.

Topics: Androstadienes; Animals; Aquaporin 5; Fluticasone; Nasal Mucosa; Piperidines; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial

Recent research has indicated that sphingosine 1-phosphate plays a role in allergy. This study examined the effect of allergen challenge on the expression of sphingosine 1-phosphate receptors on the eosinophils of allergic rhinitis patients, and the effect of steroid treatment on this expression.. A prospective, non-randomised study.. The study had three parts. Firstly, sphingosine 1-phosphate receptor expression on the eosinophils of allergic rhinitis patients and control patients was determined. Secondly, sphingosine 1-phosphate receptor expression was quantified pre- and post-allergen challenge, before and after a short course of fluticasone propionate; all patients underwent symptom scoring and peak nasal inspiratory flow measurement pre- and post-allergen challenge, both before and after steroid or saline treatment. Thirdly, the effect of sphingosine 1-phosphate on eosinophil migration was examined.. The eosinophils of both allergic rhinitis patients and controls expressed sphingosine 1-phosphate1, 3, 4, and 5. Eosinophils from all allergic rhinitis patients demonstrated up-regulation in sphingosine 1-phosphate expression after allergen challenge. These changes were statistically very significant for sphingosine 1-phosphate1, 4, and 5, and moderately significant for sphingosine 1-phosphate3. Sphingosine 1-phosphate receptor expression up-regulation was abolished in the steroid-treated group after allergen challenge; however, the saline-treated group showed no change in sphingosine 1-phosphate receptor expression after allergen challenge. Peak nasal inspiratory flow scores were significantly diminished after allergen challenge prior to treatment, but not after a course of topical nasal steroids. Sphingosine 1-phosphate induced eosinophil chemotaxis was increased following allergen challenge in allergic rhinitis subjects.. Local intranasal steroid therapy acts directly to block allergen-induced up-regulation of sphingosine 1-phosphate receptors on the peripheral eosinophils of allergic rhinitis patients, and this is coincident with post-challenge peak nasal inspiratory flow measurement improvements. These observations support the idea that such an increase in sphingosine 1-phosphate receptor expression is clinically relevant in allergic rhinitis, with potential consequences for eosinophil migration and survival.

Topics: Administration, Topical; Adult; Androstadienes; Cell Movement; Cells, Cultured; Eosinophils; Female; Fluticasone; Gene Expression; Humans; Male; Middle Aged; Nasal Provocation Tests; Prospective Studies; Receptors, Lysosphingolipid; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic, Perennial; Steroids; Up-Regulation; Young Adult

By means of the detection of the numbers of CD34(+) cells and eosinophils (EOS), and the level of IL-5 in peripheral blood from normal controls and patients with allergic rhinitis pre- or post-treatment, the role of EOS-stem cells paths for treatment effect in allergic rhinitis (AR) was studied so as to find the convenient and quick indicators which could be used to evaluate the clinical therapeutic effect and adjust the methods of the hormone therapy.. There were 2 groups. (1) experimental group: 44 patients, including 24 males and 20 females with a age range of 7 to 68 years old. The patients received the treatment of fluticasone spurt for four weeks. (2) CONTROL GROUP: 30 cases, from normal health examination. The EOS numbers, CD4(+) cell numbers and the IL-5 level were examined in control group as well as before and after therapy in experimental group.. The IL-5 level and CD numbers before therapy in experimental group were (88.25 +/- 33.47) ng/L, (9.24 +/- 2.15)/10(5), significantly higher than that after therapy and experimental group which were (44.34 +/- 16.32) ng/L, (6.31 +/- 1.83)/10(5) and (31.24 +/- 8.43) ng/L, (3.47 +/- 1.32)/10(5) respectively. The IL-5 level was positively correlated with the CD34(+) number pre-and post treatment in experimental group (r = 0.64, P <0.01; (r = 0.61, P <0.01). The EOS number was positively correlated with the level of IL-5 (r = 0.64, P <0.01).. IL-5 and CD34(+) cells can be regarded as indicators to evaluate the therapeutic effect. The EOS, CD34(+) cells and the level of IL-5 in the peripheral blood are correlated with the pathogenesis of AR, suggesting that there is a related path between the local nasal tissue of AR patients and the marrow.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Antigens, CD34; Bone Marrow Cells; Case-Control Studies; Child; Eosinophils; Female; Fluticasone; Humans; Interleukin-5; Male; Middle Aged; Rhinitis, Allergic, Perennial; Stem Cells; Young Adult

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Rhinitis, Allergic, Perennial

Topics: Administration, Intranasal; Administration, Oral; Androstadienes; Double-Blind Method; Eye Diseases; Fluticasone; Histamine H1 Antagonists; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Budesonide; Drug Administration Schedule; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Triamcinolone Acetonide

Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled fluticasone.. A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (Investigation of Montelukast as a Partner Agent for Complementary Therapy) [corrected] including 1490 adults with chronic asthma, aged 15-72 years, with FEV(1) 50-90% of predicted and > or =12% increase in FEV(1) after salbutamol administration, treated with either montelukast 10 mg daily or salmeterol 50 microg twice daily in addition to fluticasone 200 microg, was undertaken. Asthma-related medical resource use included medical visits (defined as either an unscheduled visit [to a general practitioner, a specialist or a non-medical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids.. A self-reported history of concomitant AR was identified in 60% of the patients (n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.12-4.80) and asthma attack (OR=1.35, 95% CI=1.03-1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations.. Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR.

Topics: Acetates; Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cyclopropanes; Double-Blind Method; Emergencies; Female; Fluticasone; Humans; Male; Patient Acceptance of Health Care; Quinolines; Rhinitis, Allergic, Perennial; Risk Factors; Salmeterol Xinafoate; Sulfides

Allergic rhinitis is characterized by an inflammatory response consequent to allergen exposure. Intranasal corticosteroids represent a first line treatment, but there is no adequate knowledge concerning the duration of symptomatic and antiinflammatory effects after their suspension. Thus, we aimed at investigating this issue.. Twelve children with persistent allergic rhinitis were treated with FPANS for 30 days and were followed for 12 days after its suspension. Nasal symptoms, considered as TSS, and inflammatory cells, recovered by nasal scraping, were evaluated.. FPANS significantly reduced TSS (p<0.0001), neutrophils (p<0.001), and eosinophils (p<0.0001) after 4 days of treatment. Symptoms and cellular infiltrate quickly reappeared after suspension (respectively after 3 days for symptoms (p<0.05), after 4 days for neutrophils (p<0.05), and 6 days for eosinophils (p<0.001).. These findings suggest that nasal corticosteroid treatment is highly effective in nasal symptoms' relief and inflammation's control, but its suspension induces a rapid reappearance of them.

Topics: Administration, Intranasal; Adolescent; Androstadienes; Animals; Anti-Inflammatory Agents; Child; Drug Administration Schedule; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Mites; Nasal Mucosa; Neutrophils; Recurrence; Rhinitis, Allergic, Perennial; Time Factors

To compare product attributes, preferences, and expected compliance associated with triamcinolone acetonide aqueous (TAA-AQ), fluticasone propionate (FP), and mometasone furoate (MF) nasal sprays in patients with allergic rhinitis.. Data from 2 randomized, double-blind crossover studies with identical design were pooled (N = 215). Patients completed a 14-item sensory attributes questionnaire immediately after each product, and stated their preference and expected compliance with a prescription after receiving all products.. Compared with FP and MF, TAA-AQ was associated with significantly less odor and greater liking of odor ( P < 0.001); and less taste, less dryness of nose/throat, less aftertaste, and greater overall liking ( P < 0.05). Significantly more patients preferred most a prescription of TAA-AQ (50.0%) versus FP (25.0%; P < 0.001) and MF (25.0%; P < 0.001), and would "definitely comply" with TAA-AQ (62.5%) versus FP (49.0%; P < 0.01) and MF (51.0%; P < 0.01).. TAA-AQ was associated with significantly more positive sensory attributes, higher preference, and better expected compliance than FP and MF.. Patients' preferences for the sensory attributes of an intranasal corticosteroid may affect adherence to treatment.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Patient Compliance; Patient Satisfaction; Pregnadienediols; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Triamcinolone Acetonide

Perennial allergic rhinitis (PAR) is an increasing problem for which new and exciting therapies are being developed. A T(H)2-polarized cytokine pattern is thought to predominate regulating local IgE synthesis and cell recruitment in PAR and the development of intranasal steroids has resulted in several agents with quick actions, localized effects and great efficacy in its management. The aim of work was to determine the differences in the local expression of IL-4 and IL-5 in patients with PAR compared to non-atopic healthy controls and investigate the relationship between the expression of these cytokines and the clinical aspects of the disease. Also to evaluate local expression of these cytokines in some of these patients before and after treatment with intranasal steroids (fluticasone proprionate). Nasal biopsies from 37 patients with PAR before therapy and from 8 of them after receiving corticosteroids as local nasal spray were taken. PAR was confirmed by a history of perennial nasal blockage, discharge, and/or sneeze for at least 2 years before the study and by positive skin prick test. Also nasal biopsies were taken from 20 age and gender matched non-atopic controls. Biopsies were analyzed using a reverse transcription-polymerase chain reaction (RT-PCR) to investigate local expression of IL-4 mRNA. Enzyme immunoassay was used for estimation of IL-5 levels in the nasal mucosa. By using the ROC curve; (11 pg/ml) was estimated as a cut-off value for IL-5 where levels below this cut off were considered negative. This study showed that the most common causative allergens in PAR were mite dust, followed by wool & pigeon then mixed moulds. There was a significant relation between expression of IL-4 and IL-5 and the occurrence of allergic rhinitis where mRNA of IL-4 was detected in 17/37 [46%] of patient group and in 3/20 (15%) of the control group (P < 0.05). IL-5 levels were more than the calculated cut off value in 22/37 (59.5%) of patient group as compared to 4/20 (20%) in the control group (P < 0.01). Also a high significant association was found between IL-4 & IL-5 (P < 0.01) in patient group. However, no significant relation was found between signs & symptoms of AR or patients' age or gender and cytokines expression. Corticosteroid nasal spray treatment showed a significant reduction in IL-4 gene expression and IL-5 positivity (P < 0.05). It is concluded that IL-4 & IL-5 have an important role in the pathogenesis of PAR and corticosteroid nasal spray

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Chi-Square Distribution; Child; Enzyme-Linked Immunosorbent Assay; Female; Fluticasone; Gene Expression; Humans; Interleukin-4; Interleukin-5; Intradermal Tests; Male; Middle Aged; Nasal Mucosa; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis, Allergic, Perennial; RNA

To investigate the effect of fluticasone propionate (FP) on the symptom of nasal obstruction and to assess the correlation between the subjective visual analogue score (VAS) and the objective acoustic rhinometry (AR) measurements.. A prospective study of 45 consecutive patients, 30 males and 15 females with a mean age of 27 years (range: 16-59 years), with moderate/severe symptoms of perennial rhinitis who were treated by FP nasal spray for 4 weeks. AR and VAS were used to evaluate, compare and correlate the efficacy of FP nasal sprays.. There was a significant improvement in the VAS post-treatment (3.9) compared with pre-treatment (6.3). There was also a significant increase in the nasal volume (V) and minimum cross-sectional area (MCA) after intranasal FP. Good correlation between the total MCA and total V was noted. Subjective improvements in symptoms did not correlate well with objective measurements as the correlation between VAS and AR was poor.. Our study provides subjective and objective evidence on the efficacy of intranasal FP in improving nasal obstruction in perennial rhinitis. AR also proved to be a useful instrument in monitoring the effectiveness of medical therapy for perennial rhinitis.

Topics: Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Prospective Studies; Rhinitis, Allergic, Perennial; Rhinometry, Acoustic; Treatment Outcome

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

In allergic rhinitis, allergenic stimulation causes the release of various mediators that induce symptoms and the development of chronic inflammation, which, in turn, is caused by cells involved in the late phase of inflammation, such as eosinophils. The eosinophils also cause damage at the mucosal level through the secretion of eosinophil cationic protein and other preformed factors contained in their granules. The objective was to verify the efficacy of fluticasone propionate aqueous nasal spray in patients with allergic rhinitis; in a retrospective study, we have evaluated mediators of inflammation, making correlations with the clinical symptoms score during and outside the pollen season.. Forty patients with allergic rhinitis and 15 normal controls were included in our study. Eosinophil cationic protein, eosinophil chemotactic activity, and blood and nasal lavage eosinophil count were evaluated as laboratory parameters.. We found a significant increase in nasal lavage levels of eosinophil cationic protein in allergic patients, and this was strictly correlated with the clinical symptoms score. No differences were found in the eosinophil count of allergic patients and in the serum eosinophil cationic protein of patients sensitized to seasonal allergens in comparison with normal subjects. By contrast, an increase in serum eosinophil cationic protein level was found in patients sensitized to perennial allergens. After topical administration of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage eosinophil cationic protein secretion was obtained with a reduction of eosinophil chemotactic activity at the local level. This reduction correlated with an improvement of clinical symptoms.. The clinical improvement and reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic activity after administration of fluticasone propionate aqueous nasal spray further confirms the role of this treatment in allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Blood Proteins; Chemotaxis; Child; Eosinophil Granule Proteins; Eosinophilia; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Lavage Fluid; Retrospective Studies; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Ribonucleases

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Rhinitis, Allergic, Perennial

Once-daily use of nasally applied glucocorticoids was demonstrated to be effective in the treatment of allergic rhinitis. The aim of the study was to measure concentrations of fluticasone propionate (FP) in nasal secretion and nasal tissue over a period of 1 day after a single application of 100 microg FP.. Twenty-six patients applied nasal FP spray at different time intervals before surgery. Cotton swabs, used to clean the mucosal surface, and resected nasal tissue were extracted. FP concentrations were determined by RIA.. FP was found in nasal secretions in concentrations from 15 to 1 microg/g over a period of 20 h, and in nasal tissue in concentrations from 200 to 13 ng/g up to 24 h after the single application.. The long-persisting high concentrations of FP provide the pharmacokinetic basis for once-daily treatment.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Humans; Male; Middle Aged; Mucous Membrane; Nasal Mucosa; Radioimmunoassay; Rhinitis, Allergic, Perennial; Time Factors; Treatment Outcome

In an attempt to study the pathogenesis of mucosal hypersensitivity in allergic rhinitis, we investigated the suppressive effects of cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced hypersensitivity to topical histamine challenge.. Actively sensitized Dunkin-Hartley guinea pigs.. OA and alum were applied to guinea pigs intraperitoneally 3 times at two-week intervals. After general sensitization, OA inhalation was performed every day for 6 days as topical sensitization. Before inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5 mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was measured before and after the inhalation. Moreover, in actively (general and topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5 days and histamine sensitivity was evaluated before and after the application.. We found that histamine sensitivity was significantly increased by nasal antigen challenge in this guinea pig model, and that the occurrence of histamine hypersensitivity was inhibited by the pretreatment with CyA and glucocorticosteroids. Although multiple administration of FP gradually reduced the histamine hypersensitivity according to the period of administration, it did not significantly alter the histamine hypersensitivity after the occurrence of hypersensitivity.. It is concluded that CyA and glucocorticosteroids suppress antigen-induced histamine hypersensitivity in a guinea pig model of allergic rhinitis.

Topics: Administration, Inhalation; Androstadienes; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Cyclosporine; Disease Models, Animal; Drug Hypersensitivity; Fluticasone; Glucocorticoids; Guinea Pigs; Histamine; Immunosuppressive Agents; Injections, Intraperitoneal; Male; Ovalbumin; Rhinitis, Allergic, Perennial

The use of intranasal steroids for the treatment of allergic and vasomotor rhinitis has doubled during the past 5 years. The number of reported cases of nasal septum perforation has increased correspondingly. The mechanism behind this is unknown, and steroid-induced septum perforation is rarely described in the literature. In order to describe the course of events and to form an idea of the extent of the problem, we have reviewed the cases reported at our clinic and compiled reports on side-effects from the Swedish Medical Products Agency. In our department we found 32 patients with septum perforation (21 women and 11 men). The most common risk factor for septum perforation was steroid treatment, 11 cases (10 women, 1 man, average age 33 years, range 19-49 years). The information obtained from the Swedish Medical Products Agency showed that 38 cases of steroid induced septum perforation had been reported during the past 10 years. The number of side-effects per million Defined Daily Dose (DDD) was averaged to 0.21. The risk of perforation is greatest during the first 12 months of treatment and the majority of cases involves young women. We conclude that septum perforation due to nasal sprays are underreported in Sweden and that perforations are most likely to appear in young females during their first months of medication.

Topics: Administration, Intranasal; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aerosols; Aged; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Child; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Septum; Nose Diseases; Retrospective Studies; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Rhinitis, Vasomotor; Sex Factors; Sweden; Time Factors

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Child; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

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

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Fluticasone; Humans; Rhinitis, Allergic, Perennial

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reactions and nasal polyps. We have already demonstrated that fluticasone propionate (FP) inhibits the accumulation of mast cells and eosinophils locally, and also improves the nasal symptoms of patients with allergic rhinitis. We hypothesized that cytokines generated from nasal epithelial cells possibly contribute to the accumulation of cells and eosinophils in the nasal epithelial layer. In this experiment we examined the inhibitory effect of FP on the production of GM-CSF, IL-6 and IL-8 by culturing of nasal epithelial cells in vitro. Our results show that FP significantly reduces the level of GM-CSF, IL-6 and IL-8 in the supernatant of culture media of nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days causes a significant reduction of GM-CSF levels in the supernatant of culture-media of cultured nasal epithelial cells during the subsequent period of 6 days without FP. These results provide evidence that FP inhibits the accumulation of mast cells and eosinophils in the mucoepithelial layer of the nasal membrane.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Cell Count; Cells, Cultured; Depression, Chemical; Eosinophils; Epithelium; Female; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-6; Interleukin-8; Male; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Perennial