fluticasone and Rhinitis--Allergic--Seasonal

Allergic rhinitis is a prevalent disease, which can be classed as seasonal (SAR) or perennial. In addition to nasal symptoms, up to 75% of sufferers experience itching, redness, and tearing of the eyes. Intranasal corticosteroids are effective in controlling the allergic nasal symptoms, and increasing evidence suggests that they also can relieve some of the allergic ocular symptoms.. To evaluate the magnitude of efficacy of triamcinolone acetonide (TAA) compared with placebo or fluticasone propionate (FP) on ocular symptom improvement in patients with SAR.. A meta-analysis of summary data from 8 randomized, double- or single-blind trials, assessing mean change in total or individual (tearing, redness, and itching) eye symptoms was conducted. Trials that administered a daily dose of 220 μg TAA vs placebo or 200 μg FP over at least 2 weeks' duration, in patients aged 12 years or older with SAR, were analyzed.. Total eye symptom reduction after 2 weeks was greater with TAA than placebo, with a mean treatment difference of -0.32 (95% CI, -0.444 to -0.203). In addition, significant reductions in tearing, but not itching or redness, were observed after TAA treatment compared with placebo. No significant treatment difference was seen between TAA and FP in total ocular symptoms at any of the time points measured (weeks 1, 2, 3, and overall). All treatments exhibited similar safety profiles and were deemed well tolerated.. The meta-analysis demonstrated the positive clinical improvements TAA has on total ocular allergy symptoms, especially tearing, in addition to its recognized nasal symptom efficacy in SAR.

Topics: Administration, Intranasal; Anti-Allergic Agents; Female; Fluticasone; Humans; Immunosuppressive Agents; Male; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Symptom Assessment; Treatment Outcome; Triamcinolone Acetonide

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: Androstadienes; Animals; Clinical Trials as Topic; Drug Combinations; Fluticasone; Humans; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal

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

We performed a systematic review of randomized, controlled trials to determine whether intranasal corticosteroids offered an advantage over topical antihistamines in the treatment of allergic rhinitis.. We searched for studies using MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical companies, and references of included trials.. Criteria for considering trials included: 1) published randomized controlled trials; 2) single- or double-blind studies; and 3) presence of one of the following clinical outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of life and side effects.. Nine studies including 648 subjects (mean age 30.4 years, range 13 to 73) with allergic rhinitis were selected. Intranasal corticosteroids produced significantly greater reduction of total nasal symptoms (standardized mean difference -0.36, 95% confidence interval -0.57 to -0.14), sneezing (-0.41, -0.57 to -0.24), rhinorrhea (-0.47, -0.64 to -0.29), itching (-0.38, -0.56 to -0.19), and nasal blockage (-0.86, -1.07 to -0.64) than did topical antihistamines. There was no significant difference between treatments for ocular symptoms (-0.07, -0.27 to 0.12). The effects on sneezing, rhinorrhea, itching, and ocular symptoms were significantly heterogeneous between studies. Other outcomes (total nasal symptom score and nasal blockage) were homogeneous between studies. Subgroup and sensitivity analysis suggested that most of the heterogeneity of outcomes could be explained on the basis of the methodologic quality of studies.. Intranasal corticosteroids produced greater relief of nasal symptoms than did topical antihistamines (topical H1 receptor antagonists). However, there was no difference in the relief of the ocular symptoms.

Topics: Administration, Intranasal; Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Middle Aged; Phthalazines; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Treatment Outcome

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

Adequate management of allergic rhinitis is needed to avoid its considerable adverse social, clinical, and economic impact. Both topical intranasal steroids and oral or topical antihistamines are recognised as effective treatments for this condition. In comparative studies, however, intranasal steroids and, in particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded consistently better symptomatic relief, and have a greater beneficial effect on quality of life. Furthermore, the addition of an antihistamine to FPANS therapy has generally produced little further benefit. Intranasal administration is associated with a low systemic absorption of fluticasone propionate and, following regular use of FPANS, placebo, or an oral antihistamine, no significant differences were seen between treatment groups in plasma or urinary cortisol. Overall, therefore, the data indicate that FPANS is superior to second-generation antihistamines in the management of allergic rhinitis.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Clinical Trials as Topic; Fluticasone; Histamine H1 Antagonists; Humans; Loratadine; Rhinitis, Allergic, Seasonal

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

Topics: Allergens; Androstadienes; Anti-Allergic Agents; Blood Proteins; Drug Synergism; Eosinophil Granule Proteins; Eosinophils; Fluticasone; Humans; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Nebulizers and Vaporizers; Nitrogen Dioxide; Rhinitis, Allergic, Seasonal; Ribonucleases

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

Studies have been conducted in the USA comparing fluticasone propionate aqueous nasal spray 200 micrograms once daily with beclomethasone dipropionate aqueous nasal spray 168 micrograms twice daily, oral terfenadine 60 mg twice daily, or oral astemizole 10 mg once daily given for 2 or 4 weeks during tree, grass or ragweed pollen seasons. All six were multicentre, randomised, placebo-controlled, double-blind, parallel-group studies. Efficacy was evaluated by patient and clinician assessments of individual nasal symptoms and overall response to therapy. Fluticasone propionate was superior to beclomethasone dipropionate in one trial according to patient evaluations of symptoms, but response to fluticasone propionate and beclomethasone dipropionate was similar in the second study. Comparisons with antihistamines showed fluticasone propionate to have greater efficacy. It was more effective than terfenadine in both trials according to evaluations by clinicians and patients. Similar findings were observed in the first astemizole trial. The second astemizole study showed superiority of fluticasone propionate over astemizole in terms of patient and clinician evaluations of overall response to therapy and occasionally in terms of symptom evaluations. There were no significant adverse effects, including effects on plasma cortisol concentrations, noted in any of these comparator studies.

Topics: Administration, Topical; Aerosols; Androstadienes; Anti-Inflammatory Agents; Astemizole; Beclomethasone; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Terfenadine

Fluticasone propionate is a potent topical anti-inflammatory corticosteroid with low systemic activity. Available pharmacodynamic data are only preliminary; however, large placebo- and drug-controlled clinical studies involving almost 4000 patients with seasonal allergic rhinitis and 1500 with perennial allergic and nonallergic rhinitis have confirmed the efficacy of intranasal fluticasone propionate in the control of nasal symptoms. Fluticasone propionate generally demonstrated similar efficacy compared with intranasal beclomethasone dipropionate, flunisolide acetonide and oral astemizole and better or a trend towards better efficacy compared with oral loratadine, terfenadine, cetirizine and intranasal sodium cromoglycate (cromolyn sodium) against nasal symptoms. The incidence of adverse effects in association with intranasal fluticasone propionate appears to be comparable to that observed with placebo; the most frequently reported effects are nasal dryness/burning, epistaxis and headache. Consistent with its minimal systemic availability, intranasal fluticasone propionate in a dosage of up to 4 mg/day does not cause adrenal suppression. Thus, based on early data from large clinical trials, fluticasone propionate administered once daily offers an effective and convenient treatment option in patients with seasonal and perennial allergic rhinitis, and is distinguished by its low oral bioavailability.

Topics: Administration, Intranasal; Androstadienes; Animals; Anti-Inflammatory Agents; Fluticasone; Humans; Rhinitis, Allergic, Seasonal

This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials.. A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups.. A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms.. MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Topics: Caregivers; Child; Child, Preschool; Disease Progression; Drug Combinations; Female; Fluticasone; Humans; Male; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Surveys and Questionnaires; Symptom Assessment

Allergic rhinitis (AR) is an inflammatory condition of the nasal mucosa characterized by symptoms of nasal discharge, itching, sneezing, and congestion. Ocular symptoms are commonly associated with AR and include itching or burning, tearing or watering, and redness. Intranasal corticosteroids are a mainstay of treatment, and their effect on nasal symptoms is well described.. To demonstrate that a 14-day course of 200 μg/d of nasal fluticasone propionate is superior to placebo in relieving ocular symptoms associated with AR.. This was a randomized, double-blind, parallel group, multicenter study comparing 200 μg/d of fluticasone propionate with placebo in patients with seasonal allergic rhinitis. The primary end point was mean change from baseline in patient-rated reflective total ocular symptom score (rTOSS). Key secondary end points included mean change from baseline in the morning and evening rTOSS, end-of-treatment assessment of response, and effect on activities of daily living. The primary analysis was performed using analysis of covariance with a linear fixed-effects model.. Fluticasone was statistically significantly more efficacious in reducing the ocular symptoms of AR than placebo. The least squares mean difference in the change from baseline of rTOSS was -0.36 (P = .002). A statistically significant difference in mean change from baseline was observed in favor of fluticasone for morning and evening rTOSS. Significantly more patients taking fluticasone achieved an overall response compared with placebo. Fluticasone had a significantly greater effect on daily living activities and was well tolerated.. This study supports the efficacy of fluticasone in treating ocular symptoms associated with AR.. clinicaltrials.gov Identifier: NCT01817790.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Conjunctivitis, Allergic; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Treatment Outcome; Young Adult

This study investigated improvements in quality of life associated with eight weeks of montelukast and/or intranasal steroid treatment for moderate to severe allergic rhinitis.. A single-centre, prospective, randomised, double-blind, placebo-controlled study was carried out. Assessments were made using the Rhinoconjunctivitis Quality of Life Questionnaire and symptom scales.. A total of 128 patients (aged 13-51 years) were randomly assigned to one of two groups. In the montelukast group, patients were treated with montelukast tablets and fluticasone propionate nasal spray (n = 64). In the placebo group, treatment comprised a placebo and fluticasone propionate. The results showed significant improvements in symptom scores and quality of life scores for both groups after one month and two months of treatment, compared with baseline values; these improvements were significantly greater for the montelukast group compared with the placebo group. The mean number of loratadine tablets taken by each patient during the study period was only 0.73 for the montelukast group compared with 9 for the placebo group.. The combination of montelukast tablets and fluticasone propionate nasal spray improved symptom control and overall quality of life for moderate to severe allergic rhinitis patients.

Topics: Acetates; Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Male; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Quality of Life; Quinolines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Sulfides; Surveys and Questionnaires; Treatment Outcome

It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses.. 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses.. MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom.. MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Cedrus; Disease Progression; Drug Combinations; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome; Young Adult

Current pharmacotherapy for allergic rhinitis (AR) does not totally ameliorate all symptoms for all patients. Residual symptoms could be due to nasal neuronal hyperresponsiveness caused by stimulation of the ion channel transient receptor potential vanilloid 1 (TRPV1). SB-705498 is a TRPV1 antagonist that has been developed in an intranasal formulation for treatment of AR.. This randomized, double-blind, 3-way incomplete block crossover study evaluated the effects of 8 days treatment with SB-705498 12 mg alone, SB-705498 12 mg plus fluticasone propionate 200 μg (FP), FP 200 μg alone or placebo on allergen-induced symptoms in 70 patients with AR. The primary endpoint was total nasal symptom score (TNSS), expressed as mean over 4 hours or maximum TNSS during allergen challenge in the Vienna Challenge Chamber on 8th day of treatment.. At the end of treatment, there were no differences in allergen-induced mean TNSS between SB-705498 alone and placebo or between SB-705498 plus FP and FP alone. Treatment with FP and SB-705498 plus FP resulted in a significant decrease in TNSS vs. placebo. Mean (90% CI) treatment differences in TNSS over 0 - 4 hours were: SB-705498 - placebo: -0.2 (-0.9, 0.4); SB-705498 plus FP - FP: 0.7 (0.2, 1.2); FP - placebo: -2.9 (-3.4, -2.5); SB-705498 plus FP - placebo: -2.3 (-2.8, -1.8). SB-705498 had no impact on diary card symptoms, nasal airflow or Rhinoconjunctivitis Quality of Life Questionnaire scores. SB-705498 was well tolerated and pharmacokinetics exposure results supported the dosing regimen.. SB-705498 12 mg for 8 days did not alleviate the allergen-induced symptoms of AR, or provide additional relief of symptoms when in combination with FP. Despite engagement of the TRPV1 receptor there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Austria; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Pyrrolidines; Rhinitis, Allergic, Seasonal; Treatment Outcome; TRPV Cation Channels; Urea

In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP.. In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16-85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph.. Initial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season.. Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Sprays; Pollen; Rhinitis, Allergic, Seasonal; Tablets; Terfenadine; Treatment Outcome

• The topical second generation anti-histamine azelastine hydrochloride (AZE) and the potent corticosteroid fluticasone propionate (FP) are well established first-line treatments in allergic rhinitis (AR). • MP29-02, a novel intranasal AZE and FP formulation, has been shown to control AR symptoms faster and better than standard intranasal AZE or FP. • The systemic bioavailabilities of marketed AZE and FP nasal spray products have been established at about 40% and 1% only, respectively. • For new combination medicinal products such as MP29-02, the determination of possible pharmacokinetic (PK) drug-drug interactions between both active components and formulation-based bioavailability alterations is essential.. • This paper provides for the first time information on potential drug-drug interactions, AZE and FP bioavailability and disposition characteristics of each component administered by the novel nasal spray formulation MP29-02. • The studies employed highly sensitive FP and AZE LC-MS/MS assays and could therefore be conducted with recommended therapeutic doses, thereby circumventing previously recognized draw-backs that required nasal bioavailability studies to be conducted using supra-therapeutic doses. • No significant PK drug-drug interaction between the active components AZE and FP was noted for MP29-02. • AZE bioavailabilty was equivalent when MP29-02 data were compared with MP29-02-AZE-mono and Astelin®. • Increased FP exposure was observed with MP29-02-based products compared with FP-BI. FP serum concentrations were generally very low with all investigational products suggesting no clinically meaningful pharmacodynamic differences in terms of systemic safety.. To determine azelastine hydrochloride (AZE) and fluticasone propionate (FP) bioavailabilities of the novel nasal spray combination product MP 29-02, compared with MP29-02-based products containing only AZE (MP29-02-AZE-mono), FP (MP29-02-FP-mono), marketed AZE and FP single entity products (Astelin® and FP Boehringer-Ingelheim; FP-BI).. Two randomized, three period, six sequence, three treatment crossover studies were conducted in healthy subjects. Study 1 administered 200 µg FP as MP29-02, MP29-02-FP-mono or FP-BI. Study 2 administered 548 µg AZE as MP29-02, MP29-02-AZE-mono or Astelin®. Each dose consisted of two sprays/nostril. Serum FP and plasma AZE were followed over 24 (FP) and 120 h (AZE) and quantified by LC-MS/MS. Peak (C(max) ) and total exposures AUC(0,t(last) ) were compared between the treatments by anova.. Study 1: Average FP C(max) was very low with all products (≤ 10 pg ml(-1) ). FP AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-FP-mono and MP29-02 : FP-BI ratios (%) were 93.6 (83.6, 104.7) and 161.1 (137.1, 189.3). Corresponding ratios for C(max) were 91.0 (82.5, 100.4) and 157.4 (132.5, 187.1). Study 2: AZE AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-AZE-mono and MP29-02 : Astelin® ratios (%) were 98.8 (91.0, 107.4) and 105.5 (95.6, 116.4). Corresponding outcomes for C(max) were 102.7 (92.1, 114.4) and 107.3 (92.6, 124.3).. No interactions of AZE and FP were found with the MP29-02 formulation. Azelastine bioavailability was similar for MP29-02 and Astelin®. Maximum and total FP exposure was higher for MP29-02-based products compared with FP-BI. FP concentrations were generally very low with all investigational products and did not suggest clinically meaningful differences concerning systemic safety.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Biological Availability; Chromatography, High Pressure Liquid; Drug Combinations; Drug Delivery Systems; Drug Interactions; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal; Tandem Mass Spectrometry; Young Adult

Moderate-to-severe allergic rhinitis (AR) is a challenge to treat, with many patients using multiple therapies and achieving limited symptom control. More effective therapies must be developed and tested in well-controlled, randomized, prospective studies with a direct comparison to current standards.. The aim of these studies was to investigate the efficacy of MP29-02 (a novel formulation of azelastine and fluticasone propionate [FP]) in patients with moderate-to-severe seasonal allergic rhinitis (SAR) and to compare its efficacy with 2 first-line therapies (ie, intranasal azelastine and intranasal FP) in this population.. Three thousand three hundred ninety-eight patients (≥12 years old) with moderate-to-severe SAR were enrolled into 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group trials (MP4002 [NCT00651118], MP4004 [NCT00740792], and MP4006 [NCT00883168]). Each trial was conducted for 14 days during different allergy seasons. The primary efficacy variable was the sum of the morning and evening change from baseline in reflective total nasal symptom score (range, 0-24) over the treatment period. Outcomes for the meta-analysis included efficacy according to disease severity and time to response in relevant responder criteria.. In the meta-analysis MP29-02 reduced the mean reflective total nasal symptom score from baseline (-5.7 [SD, 5.3]) more than FP (-5.1 [SD, 4.9], P < .001), azelastine (-4.4 [SD, 4.8], P < .001), or placebo (-3.0 [SD, 4.2], P < .001). This benefit was observed from the first day of assessment, with improvement in each individual nasal symptom, even in the patients with the most severe disease. MP29-02 achieved response consistently days earlier and showed greater efficacy in patients with moderate-to-severe rhinitis than FP and azelastine.. MP29-02 represents a novel therapy that demonstrated superiority to 2 first-line therapies for AR. Patients with moderate-to-severe SAR achieved better control, and their symptoms were controlled earlier with MP29-02 than with recommended medications according to guidelines.

Topics: Administration, Intranasal; Adult; Androstadienes; Disease Progression; Drug Combinations; Female; Fluticasone; Guidelines as Topic; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Seasons; Severity of Illness Index; Young Adult

To determine and compare patient-relevant settings for automated nasal spray actuation stations from adult and pediatric hand data.. Twenty adults and 20 pediatric participants were asked to spray Flonase(®) Nasal Spray six times in a Hand Actuation Monitor, which records force and displacement data in 5-ms increments. Settings for force- and velocity-controlled actuation stations were determined from the data using a predefined set of calculations.. For force-controlled settings, hand spraying by children resulted in lower actuation forces, and longer force rise, hold and fall times. Pediatric velocity-controlled actuator settings were lower for travel, compression velocity, and release velocity compared with adults. The pediatric spray weight recorded during hand spraying was significantly lower than the spray weight generated by adult participants. Adult participants were able to generate full sprays with each attempt, whereas 11 out of 120 actuations performed by pediatric participants resulted in partial and 'no spray' events. No differences in spray weight were detected in participants who chose to actuate the nasal spray using both hands.. A predefined set of calculations was used to determine patient-relevant settings from force and displacement hand data for force- and velocity-controlled automated actuation stations. This study determined and quantified, for the first time, the differences in hand spraying between adults and children.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Child; Fluticasone; Humans; Middle Aged; Nasal Sprays; Pressure; Rhinitis, Allergic, Seasonal; Time Factors

IL-13 is a key T(H)2 cytokine that is implicated in allergic responses.. We evaluated the effects of an anti-IL-13-blocking antibody compared with placebo on repeated nasal allergen challenge responses in hay fever patients out of season.. We performed a parallel group double-blind study of anti-IL-13 (single dose, 6 mg/kg intravenously, n = 16) and placebo (n = 15), with an additional open label group given a topical nasal corticosteroid (n = 5). Subjects received intranasal timothy grass pollen (Phleum pratense P5 allergen), and serial samples of nasal mucosal lining fluid were taken by using synthetic absorptive matrix and by nasal lavage.. Administration of anti-IL-13 on day 1 resulted in a significant decrease in IL-13 levels in synthetic absorptive matrix eluates compared with placebo (area under the curve 0-8 hours, change from baseline) during the late phase after nasal allergen challenge on day 5 (P < .05) and day 7 (P < .01). There were no apparent effects of anti-IL-13 treatment on nasal lavage eosinophil numbers or total nasal symptom scores versus placebo. However, in a subgroup with high late-phase IL-13 levels at screening, there was a trend for a decrease in total nasal symptom scores after nasal allergen challenge on day 5, when compared with subjects with low IL-13 levels (P < .10). Nasal fluticasone caused suppression of IL-13 (P < .05 on day 5) as well as IL-5 (P < .01 on day 5) levels in the late phase compared with placebo.. Anti-IL-13 had specific pharmacodynamic action in this nasal allergen challenge model, causing profound inhibition of nasal lining fluid IL-13 responses. In addition, there was a possible effect of anti-IL-13 treatment on total nasal symptom scores in a subgroup with high late-phase nasal IL-13 levels at screening.

Topics: Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Antibodies, Monoclonal; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Interleukin-13; Male; Middle Aged; Phleum; Rhinitis, Allergic, Seasonal; Therapeutic Irrigation

Allergic rhinitis is a common upper respiratory tract inflammation associated with a significant morbidity in all the age groups. Fluticasone furoate is a new potent topical glucocorticoid for the treatment of allergic rhinitis.. To compare efficacy and safety of fluticasone furoate (FF) nasal spray 110 microg/day with fluticasone propionate (FP) nasal spray 200 microg/day for the relief of symptoms of allergic rhinitis in adult Indian patients.. Clinically symptomatic patients (n=220) with allergic rhinitis received treatment with FF or FP for 2 weeks in this comparative, open label, multicentric, clinical trial. Nasal symptoms (nasal congestion, rhinorrhea, nasal itching, and sneezing) and ocular symptoms (itching/burning eyes, tearing/watering eyes, and eye redness) were recorded on a 4-point categoric scale by the patients. The efficacy was assessed by the change in nasal and ocular symptom scores as their subtotals (Total Nasal Symptom Score and Total Ocular Symptom Score) and grand total (Total Symptom Score).. FF produced significantly better improvement in Total Symptom Score (-10.4 +/- 3.2 vs. -8.9 +/- 3.5, p<0.005) and Total Nasal Symptom Score (-7.3 +/- 2.2 vs. -6.2 +/- 2.6, p<0.005) as compared to FP. Also a significantly larger percentage of patients achieved complete symptomatic relief with FF (45.3% vs. 31.4%, p<0.05). FF was also better tolerated than FP.. FF nasal spray is significantly more effective and better tolerated than FP nasal spray for the treatment of allergic rhinitis in adult Indian patients.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; India; Male; Middle Aged; Nasal Sprays; Rhinitis, Allergic, Seasonal; Treatment Outcome

Intranasal corticosteroids are first-line treatment for moderate-to-severe seasonal allergic rhinitis (AR).. To compare preferences for fluticasone furoate and fluticasone propionate nasal sprays after 1 week of treatment in patients with symptomatic seasonal AR.. Patients with seasonal AR were enrolled (n = 360) and randomized 1:1 to active treatment (fluticasone furoate, 110 microg, or fluticasone propionate, 200 microg, followed by crossover treatment for 1 week each) or matched placebo sequence with a 1-week washout before crossover dosing. Fluticasone furoate and fluticasone propionate efficacy was measured by change from baseline during 1 week in daily reflective total nasal symptom score (rTNSS) that assessed severity of rhinorrhea, nasal congestion, nasal itching, and sneezing. Patient preference for fluticasone furoate or fluticasone propionate was assessed at the end of the study by questionnaire.. Three hundred sixty patients from 29 clinical sites in the Unites States were randomized and treated between August 1, 2007 and November 30, 2007. Most patients were white (73%) and female (59%), with a mean age of 38.3 years, and had had seasonal AR for at least 10 years (74%). Fluticasone furoate and fluticasone propionate each reduced the daily rTNSS compared with their respective placebos (least squares mean [SD] difference, -0.8 [0.24], P < .001, and -0.6 [0.24], P = .01, respectively). More patients (P < .001) preferred fluticasone furoate to fluticasone propionate based on attributes of scent or odor (58% vs 27%), aftertaste (60% vs 18%), leaking out of the nose and down the throat (59% vs 21%), and mist gentleness (57% vs 26%). No statistically significant differences were seen in preferences regarding ease of use, delivery method, or device comfort.. Both fluticasone furoate and fluticasone propionate significantly improved symptoms in adult patients with seasonal AR. Most patients preferred the sensory attributes of fluticasone furoate to those of fluticasone propionate after 1 week of treatment.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Patient Preference; Placebos; Rhinitis, Allergic, Seasonal; Sensation; Smell; Surveys and Questionnaires; Taste; Treatment Outcome

A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone.. To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray.. This 14-day, multicenter, randomized, double-blind study was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in, 610 patients with moderate-to-severe nasal symptoms were randomized to treatment with (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All treatments were given as 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing.. All 3 active groups were statistically superior (P

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Aged; Allergens; Androstadienes; Cedrus; Child; Double-Blind Method; Drug Combinations; Drug Synergism; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Pollen; Rhinitis, Allergic, Seasonal

To our knowledge, there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid, although anecdotal reports of the use of these agents in combination are common.. To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone.. This randomized, 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms were randomized to treatment with the following: (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion.. All 3 groups had statistically significant (P < .001) improvements from their baseline TNSS after 2 weeks of treatment. The TNSS improved 27.1% with fluticasone nasal spray, 24.8% with azelastine nasal spray, and 37.9% with the 2 agents in combination (P < .05 vs either agent alone). All 3 treatments were well tolerated.. The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Headache; Humans; Male; Middle Aged; Phthalazines; Rhinitis, Allergic, Seasonal; Taste; 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

Fluticasone furoate (USAN-approved name) is a novel, enhanced-affinity glucocorticoid administered in a unique side-actuated device for the management of seasonal allergic rhinitis (SAR).. We sought to evaluate the efficacy and safety of once-daily fluticasone furoate nasal spray, 110 microg, in patients aged 12 years or older with fall SAR.. Patients (n = 299) received fluticasone furoate or placebo for 2 weeks in this double-blind, parallel-group randomized study. Patients evaluated nasal and ocular symptoms using a 4-point categoric scale. Efficacy was assessed on the basis of the mean change from baseline in reflective and instantaneous total nasal symptom scores and reflective total ocular symptom scores.. Fluticasone furoate produced significantly greater improvements than placebo in daily reflective total nasal symptom score (-1.473, P < .001; primary end point), morning predose instantaneous total nasal symptom score (-1.375, P < .001), daily reflective total ocular symptom score (-0.600, P = .004), and patient-rated overall response to therapy (P < .001). The onset of therapeutic effect occurred at 8 hours after initial administration. Fluticasone furoate was well tolerated.. Fluticasone furoate, 110 microg once daily, was effective and well tolerated for the treatment of nasal symptoms of SAR in patients aged 12 years and older. Treatment also produced significant improvements in ocular symptoms. Fluticasone furoate was fast acting, as indicated by an 8-hour onset of action, and provided 24-hour symptom control.. New treatments for the bothersome symptoms of SAR are needed. One such treatment, fluticasone furoate nasal spray, provides effective relief of the symptom profile of SAR.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Ambrosia; Androstadienes; Anti-Inflammatory Agents; Child; Dose-Response Relationship, Immunologic; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal

T-regulatory cells (Treg) affect the balance of T(H)2 and T(H)1 cells. Treg, T(H)2 and T(H)1 cells are regulated by the FOXP3, GATA-3 and T-bet transcription factors respectively. Our aim was to determine the number of FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa in symptom-free allergic rhinitis (AR) patients vs healthy controls, as well as the effects of natural pollen exposure and concomitant nasal glucocorticoid treatment on these cells.. Nasal biopsies were taken from healthy controls and patients with grass-pollen AR preseason. The AR patients were randomized to receive treatment with either fluticasone propionate (FP) or a placebo, and additional biopsies were taken during the pollen season. FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa were quantified by immunohistochemistry.. The number of FOXP3(+) and GATA-3(+) cells, but not T-bet(+) cells, was significantly higher in AR patients vs controls preseason. The number of FOXP3(+) cells remained unchanged in the former group after the pollen season but decreased significantly in the nasal mucosa as a result of FP treatment. The pollen season substantially increased the number of GATA-3(+) cells, which was inhibited by FP. The number of T-bet(+) cells was not affected by pollen or FP.. These data suggest that nasal glucocorticoids attenuate the allergic inflammation partly by reducing the number of T(H)2 cells, but not by means of local upregulation of Treg cells. The local relationship between T(H)1 and T(H)2 cells as well as between Treg and T(H)2 is maintained by nasal glucocorticoid treatment.

Topics: Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Female; Fluticasone; Forkhead Transcription Factors; GABA Plasma Membrane Transport Proteins; Glucocorticoids; Humans; Male; Middle Aged; Nasal Mucosa; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; T-Box Domain Proteins; Th2 Cells

Fluticasone furoate is a new enhanced-affinity glucocorticoid with a unique combination of pharmacodynamic and physicochemical properties suitable for topical activity.. In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, patients [adults and adolescents >or=12 years of age with seasonal allergic rhinitis (SAR)] received once-daily (od) treatment for 2 weeks with either fluticasone furoate nasal spray 110 microg (n = 141) or placebo nasal spray (n = 144) administered in a unique, side-actuated device. Efficacy measures included total nasal symptom score (TNSS) and total ocular symptom score (TOSS). Patients also reported their overall response to therapy and rated their quality of life using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ).. Fluticasone furoate significantly improved the mean change from baseline in daily reflective TNSS compared with placebo (treatment difference of -1.757; P < 0.001). Fluticasone furoate was also significantly more effective in improving the morning predose instantaneous TNSS (treatment difference of -1.898; P < 0.001) and daily reflective TOSS (treatment difference of -0.741; P = 0.001). A significant treatment effect was observed as early as day 1. Compared with placebo-treated patients, fluticasone furoate-treated patients showed significantly greater improvements in overall evaluation of response to therapy (P < 0.001), as well as in overall RQLQ score (P < 0.001). Fluticasone furoate was well tolerated.. Fluticasone furoate nasal spray 110 mug od was effective in improving the nasal symptoms of SAR. It also produced significant improvements in ocular symptoms.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Allergens; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Europe; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients.. To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels.. Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs.. The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients.. Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Bronchi; Cysteine; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotrienes; Male; Rhinitis, Allergic, Seasonal; Vital Capacity

Addition of H(1) antagonists to intranasal corticosteroid treatment of allergic rhinitis (AR) is common in clinical practice and recommended by guidelines, despite some evidence that the additive benefits are negligible.. To assess additional benefits of 5 mg levocetirizine dihydrochloride in seasonal AR patients using 200 mcg fluticasone propionate nasal spray once daily.. In a double-blind placebo-controlled crossover study of 27 patients, following 2 weeks without treatment, subjects used fluticasone with levocetirizine or identical placebo for 2 weeks each. Assessments were the Juniper mini Rhinoconjunctivitis Quality-of-Life Questionnaire (mini-RQLQ), domiciliary peak nasal inspiratory flow (PNIF), total nasal symptoms (TNS) scores and nasal nitric oxide concentrations. Effects were interpreted and tested against minimal clinically important differences.. Add-on effects for levocetirizine vs. placebo excluded any clinically significant benefits: mean effects (one sided 95% confidence intervals) were mini-RQLQ -0.11 (-0.34), PNIF +0.57 (+5.23), and TNS -0.11 (-0.60). Numbers needed to treat (95% confidence intervals) by outcome were mini-RQLQ 14 (5 to 49), PNIF 4 (3-7), and TNS 3 (2-6). No significant within or between treatment effects were seen for nasal nitric oxide.. Contrary to current practice, the present results demonstrate that for the majority of patients, antihistamine add-on to effective nasal steroid treatment is inappropriate. Further work is required to confirm that this is also true in the most severe cases, and the available evidence needs to be put into guidelines and implemented.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Cetirizine; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Histamine H1 Antagonists, Non-Sedating; Humans; Inhalation; Male; Middle Aged; Nitric Oxide; Nose; Piperazines; Pollen; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome

Combination of inhaled steroid and long-acting beta-agonists has synergistic effects in asthma.. To investigate whether nasal corticosteroid and long-acting beta-agonists have synergistic effects on allergen-induced nasal responses.. The effects of intranasal treatment with fluticasone p-MDI (50 microg bid), salmeterol p-MDI (25 microg bid), their combination, and placebo, on nasal symptoms, eosinophil differential cell count and albumin in nasal lavage fluid (measures of inflammation and leakage respectively) and nasal electrical potential difference (measure of epithelial integrity) were studied in 11 atopic subjects with rhinitis, in a randomized, partially-blinded, 4-period, cross-over study. The measurements were made at baseline, at the end of 1 week of treatment, and immediately after a nasal allergen provocation.. Allergen-induced sneeze, postnasal drip and nasal obstruction were significantly reduced by fluticasone, but not by salmeterol. Eosinophil count in postallergen nasal lavage fluid was significantly less after fluticasone (median 1.9%, IQR 4.6) and salmeterol treatment (median 2.5%, IQR 8.5) compared with placebo (median 12.5%, IQR 27.9). Compared with placebo, both fluticasone and salmeterol attenuated allergen-induced change in nasal potential (mean change from baseline -18.5, +0.4 and -7.2% respectively) and the increase in nasal albumin (median 154, 119 and 130 ng/ml respectively). Combination treatment did not have any additional benefits over the individual therapies.. Although salmeterol has anti-inflammatory properties, intranasal salmeterol or its combination with fluticasone do not offer any added benefit over intranasal fluticasone alone for allergen-induced nasal responses.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Bronchodilator Agents; Cross-Over Studies; Drug Synergism; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Membrane Potentials; Nasal Lavage Fluid; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Nebulizers and Vaporizers; Rhinitis, Allergic, Seasonal; Salmeterol Xinafoate

Few studies have directly compared the efficacy of intranasal corticosteroids with that of leukotriene receptor antagonists for the treatment of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR).. To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with oral montelukast, 10 mg daily, for the relief of SAR symptoms.. Patients with SAR 15 years or older were randomized to receive either fluticasone propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy, parallel-group study. The primary efficacy measure was the mean change from baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime individual nasal symptom scores [INSSs] assessing nasal congestion, itching, rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2.. Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P < .001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed significant differences favoring fluticasone propionate over montelukast across 2 weeks of treatment.. Compared with montelukast, fluticasone propionate provided significantly greater improvement in daytime and nighttime SAR symptoms.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Multicenter Studies as Topic; Nebulizers and Vaporizers; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides; Texas

Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood.. We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4-positive cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is a potent chemoattractant for haematopoietic progenitors.. In a double-blind, randomized study, pollen-sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 microg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry.. The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP-treated patients was lower compared with placebo-treated patients.. A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.

Topics: Adolescent; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Antigens, CD34; Chemokine CXCL12; Chemokines, CXC; Eosinophils; Fluticasone; Humans; Immunohistochemistry; Nasal Mucosa; Nasal Provocation Tests; Receptors, CXCR4; Rhinitis, Allergic, Seasonal; Statistics, Nonparametric; Stem Cells; T-Lymphocytes

Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma.. A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts.. Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness.. In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Comorbidity; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

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

Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders.. This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods.. Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC.. Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected.. Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Topics: Adrenal Cortex Hormones; Adult; Allergens; Analysis of Variance; Androstadienes; Female; Fluticasone; Humans; Interleukin-13; Interleukin-4; Interleukin-5; Interleukins; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Single-Blind Method

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

Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms.. We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season.. One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage.. All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK.. The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Topics: Acetates; Administration, Intranasal; Adolescent; Adult; Analysis of Variance; Androstadienes; Blood Proteins; Cetirizine; Child; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eosinophil Granule Proteins; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Rhinitis, Allergic, Seasonal; Ribonucleases; Sulfides

Concern has been directed at the relative sedating properties of lipophilic and lipophobic antihistamines, but few studies have sought to determine the comparative benefit of seasonal allergic rhinitis (SAR) treatments in controlling symptoms and consequently improving alertness.. To compare the relative contributions of fluticasone propionate aqueous nasal spray and loratadine in enhancing daytime performance in 8- to 17-year-old children.. All participants had a documented history of SAR, positive response to a skin prick (wheal 3-mm greater than negative control or equal to the positive control) for seasonal aeroallergens, and clinically identifiable symptoms at the time of randomization. Following confirmation during baseline of current SAR symptoms, participants were randomized to 1 of the 2 treatments and returned 2 weeks later for evaluation of symptom control, quality of life, attention, reaction time, and memory.. Children in the fluticasone propionate aqueous nasal spray group but not the loratadine group demonstrated improvement in nasal symptoms, nasal quality of life score, and composite verbal memory. No differences were identified on any scores from the Conners Continuous Performance Test.. Treatments that most effectively control SAR symptoms are also likely to provide the greatest benefit to children whose daytime functioning, including their capacity to learn at school, is compromised by their illness.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Androstadienes; Anti-Allergic Agents; Child; Female; Fluticasone; Humans; Loratadine; Male; Psychomotor Performance; Rhinitis, Allergic, Seasonal; Sleep Stages

If monotherapy with an intranasal corticosteroid can alleviate both nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and costs may be reduced.. The purpose of this study was to evaluate the efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular symptoms associated with seasonal allergic rhinitis.. A total of 471 patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind, double-dummy, randomized study. Patients were > or =12 years old with a history of seasonal allergic rhinitis and a positive skin test for a relevant allergen. During the baseline and treatment periods, patients rated the severity of eye itching, tearing, and redness via visual analogue scales that ranged from 0 (no symptoms) to 100 (most severe symptoms). The three ocular ratings were added to derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on at least 4 of the 7 days before the randomization visit were enrolled. The primary outcome was the difference between FP and vehicle placebo in the mean change from baseline in the reflective TOSS overall (averaged over the 28-day treatment period). A difference between FP and vehicle placebo of 25.5 was considered clinically significant.. The overall mean change from baseline in the TOSS was significantly greater in the FP group compared with vehicle placebo (clinically significant difference of 28.8; P<0.001) and compared with LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4) for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP group. The FP treatment group also showed significantly greater overall mean changes in ocular itching, tearing, and redness compared with vehicle placebo (P<0.001) and compared with LOR (P< or =0.045).. Patients treated with intranasal FP had clinically and statistically significant decreases in ocular symptom scores compared with vehicle placebo. Data also suggest that FP reduced ocular symptoms more than or comparable with oral LOR. Patients experiencing ocular symptoms associated with allergic rhinitis may benefit from monotherapy with intranasal FP.

Topics: Administration, Topical; Adult; Aerosols; Androstadienes; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Rhinitis, Allergic, Seasonal; Sample Size

The aim of the study was to examine the level of sICAM-1 in serum of patients suffering from allergic rhinitis treated with fexofenadine or fluticasone. The study was performed after two weeks' duration of the pollen season. Thirty -eight patients sensitized to grass pollen were participated in this study: 15 patients were treated for 10 days with oral fexofenadine (dose: 120 mg/d), 13 patients were treated with intranasal fluticasone (dose: 200 mcg/d), 10 patients were given oral placebo. Blood sample were collected both in the first and the last day of the treatment. The efficacy was evaluated with the use of symptom score. sICAM-1 level in serum was measured with ELISA method.. Mean sICAM-1 level in serum was: in group treated with fexofenadine- 224,5 ng/ml before treatment, 228 ng/ml - after treatment; in group treated with fluticasone- 212 ng/ml before treatment, 214 ng/ml- after treatment; in placebo group- 226 ng/ml before treatment, 229 ng/ml- after treatment. There was no difference in statistical analysis between sICAM-1 values. (p > 0.05). In 7 patients treated with fexofenadine serum levels of sICAM-1 significantly decreased from 212 ng/ml to 185 ng/ml (p < 0.05), the same decrease was observed in 7 patients treated with fluticasone: from 233 ng/ml to 209 ng/ml (p < 0.01), and in 6 patients from placebo group: from 219 ng/ml to 205 ng/ml (p < 0.01). However in the rest of patient's level of sICAM-1 significantly increased after treatment. Patients treated with fexofenadine showed significant improvements of clinical symptoms (mean symptom score before treatment: 11, 3, after treatment-5, 3) and symptoms evaluated during laryngological examination (mean symptom score before treatment: 9, 5, after treatment- 5, 5). Significant improvement of clinical symptoms was also observed in patients treated with fluticasone (mean symptom score before treatment: 10, 7, after treatment 3, 6) and symptoms evaluated during laryngological examination (mean symptom score before treatment: 9, 2, after treatment- 5, 0). No changes were noticed in placebo group (mean clinical symptom score before treatment: 9, 0, after treatment 10, 3 and mean laryngological symptom score before treatment: 7, 5, after treatment 7, 7).

Topics: Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Female; Fluticasone; Humans; Intercellular Adhesion Molecule-1; Male; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome

To compare the effectiveness of an intranasal steroid treatment with that of the combination of a histamine1 receptor antagonist and a leukotriene D receptor antagonist in the treatment of seasonal allergic rhinitis.. A 2-week, parallel, randomized, double-blind, double-dummy study with rolling enrollment.. Tertiary care medical center. Subjects A total of 63 adults with a 2-year history of ragweed sensitivity in the Chicago, Ill, area and a positive skin-prick reaction to ragweed pollen. Intervention Subjects were randomized to receive either 100 micro g of fluticasone propionate aqueous nasal spray in each nostril or 10 mg of loratadine and 10 mg of montelukast sodium by mouth once daily in the evening for 2 weeks. At visits 1 and 2, subjects completed a quality-of-life questionnaire and underwent nasal lavage to determine total eosinophil count and eosinophil cationic protein (ECP) measurements. Daily symptom diaries were kept for 2 weeks.. Questionnaire answers, daily nasal symptom scores, eosinophil counts, and ECP levels.. Median total nasal symptom scores were lower in the fluticasone group (4.5 vs 6), but the difference was not statistically significant. The questionnaire answers showed dramatic improvement in overall and individual domains for both groups (P<.01 vs visit 1) with significantly greater reduction in nasal symptoms in the fluticasone group (P<.05). Eosinophil counts and ECP levels were significantly reduced in the fluticasone group.. Both treatments provided clinically meaningful responses, but the overall results favored fluticasone propionate.

Topics: Acetates; Adult; Androstadienes; Anti-Inflammatory Agents; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides

The safety and efficacy of intranasal corticosteroids for the treatment of allergic rhinitis is well documented in the literature. Additionally, an expert panel has concluded that intranasal corticosteroids are the first line of therapy when obstruction is a major component of rhinitis. Montelukast is a leukotriene receptor antagonist recently approved for the treatment of seasonal allergic rhinitis (SAR).. This randomized, double-blind, double-dummy, parallel-group study was conducted to compare the effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg, once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in relieving daytime and nighttime nasal symptoms associated with SAR.. The intent-to-treat (ITT) analysis population consisted of 705 eligible males and females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or MON10QD (N = 352). The primary efficacy endpoint was the mean change from baseline in subject-rated daytime total nasal symptom scores (the sum of four individual scores: nasal congestion, itching, rhinorrhea, and sneezing), evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary endpoints included the four daytime individual nasal symptom scores, the nighttime total, and individual nasal symptom scores (each evaluated on a four-point scale from 0 to 3).. Statistically significant differences favoring FP200QD over MON10QD were observed for the mean change from baseline in daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD were both well tolerated.. The results of this well controlled study demonstrated that FP200QD was consistently superior to MON10QD with regard to every efficacy endpoint evaluated, including daytime and nighttime nasal congestion, in subjects with SAR.

Topics: Acetates; Administration, Intranasal; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Female; Fluticasone; Humans; Leukotriene Antagonists; Loratadine; Male; Nasal Obstruction; Pruritus; Quinolines; Rhinitis, Allergic, Seasonal; Sneezing; Sulfides

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

We compared 220 microg daily intranasal aqueous triamcinolone acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief of seasonal allergic rhinitis symptoms. Study design and setting Randomized, parallel-group, investigator-blind study included patients with symptomatic seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity was recorded twice daily; total nasal symptom score was calculated. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire.. Reductions in individual symptoms and total nasal symptom score were statistically significant versus baseline and were equivalent between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17 +/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391 to 0.3693). Clinically and statistically significant improvements in Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable.. TAA AQ and FP were equally efficacious in relieving seasonal allergic rhinitis symptoms and improving health-related quality of life.. Differences in molecular potency of intranasal steroids do not confer differences in efficacy.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Rhinitis, Allergic, Seasonal; Single-Blind Method; Treatment Outcome; Triamcinolone Acetonide

Few published clinical trials document the efficacy of intranasal corticosteroids used as needed for treatment of seasonal allergic rhinitis.. To evaluate the efficacy and safety of 4 weeks' treatment with fluticasone propionate aqueous nasal spray 200 microg used as needed (FP200PRN) in patients with seasonal allergic rhinitis.. A randomized, double-blind, placebo-controlled study in 241 patients (> or = 12 years of age) with a positive skin test result to a relevant fall allergen and who were symptomatic at randomization. The primary endpoint was the mean change from baseline in total nasal symptom score (TNSS; the sum of nasal congestion, rhinorrhea, sneezing, and nasal itching, each rated on a 4-point scale from 0 = none to 3 = severe).. The mean percentage of days that patients used the study medications in the FP200PRN and placebo groups was 61.8% (SD = 30.4%) and 70.1% (SD = 28.3%), respectively. Patients treated with FP200PRN had a significantly greater reduction from baseline in TNSS compared with those treated with vehicle placebo (mean +/- SE = -2.02 +/- 0.18 vs -1.06 +/- 0.22, P < 0.001), representing a 91% greater improvement with FP200PRN than vehicle placebo. The FP200PRN group also had a significantly greater (P < 0.001) mean reduction in individual nasal symptoms of rhinorrhea, sneezing, nasal itching, and nasal congestion compared with placebo. FP200PRN was well tolerated, with an incidence of adverse events comparable to vehicle placebo.. FP200PRN in patients 12 years and older is effective for treatment of nasal symptoms associated with seasonal allergic rhinitis. It has a lower incidence of adverse events than typically associated with regular once-daily use.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Rhinitis, Allergic, Seasonal; Sneezing

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

Immunotherapy is a recognized treatment for allergic respiratory diseases.. To study the usefulness of immunotherapy in combination with optimal pharmacological therapy.. Thirty-eight children (8-14 years) suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly controlled by anti-allergic drugs treatment were selected. After randomization according to a double-blind placebo-controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season.. Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group.. The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non-bronchial symptoms.

Topics: Administration, Inhalation; Administration, Sublingual; Adolescent; Allergens; Androstadienes; Anti-Allergic Agents; Asthma; Child; Combined Modality Therapy; Desensitization, Immunologic; Double-Blind Method; Female; Fluticasone; Humans; Male; Parietaria; Plant Proteins; Pollen; Rhinitis, Allergic, Seasonal; Skin; Treatment Outcome

The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR).. To compare the efficacy, safety, and effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal sprays in patients with SAR.. Single-blind, parallel-group, active-controlled design. Patients were randomized to 3-week treatment with TAA 220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) were performed AM/PM, beginning at pretreatment baseline period. Incidences of specific treatment-related side effects were collected in daily questionnaires. HRQL was evaluated at baseline and end-of-treatment with a validated disease-specific, quality-of-life instrument.. TAA and FP produced similar improvement in daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P = 0.332) and at every weekly time point (P > 0.05). There were no significant differences between TAA and FP in any individual symptom score at any time point except week 2 (FP provided greater reduction in sneezing, P = 0.046). No significant difference was found between groups in overall occurrence of specific treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life Questionnaire scores were similar for TAA and FP at end-of-treatment.. Despite differing molecular potencies, FP and TAA demonstrated comparable efficacy in the treatment of SAR, and produced similar occurrences of specific treatment-related side effects and similar improvements in overall patient HRQL.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Rhinitis, Allergic, Seasonal; Single-Blind Method; Triamcinolone Acetonide

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

Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis.. We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid.. In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops and a limited amount of loratadine were allowed as rescue medication for severe symptoms. Patients recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens were obtained from patients for evaluation of local eosinophilic inflammation.. During the peak season, both FPANS and combined montelukast-loratadine were significantly more effective than placebo and montelukast alone for daytime symptom prevention. For nighttime symptoms, FPANS was significantly more effective compared with all other treatments, whereas combined montelukast-loratadine and montelukast alone did not provide significant symptom prevention compared with placebo. The pollen-induced increase in the numbers of epithelial eosinophils was significantly lower for FPANS-treated patients compared with that seen in all other treatment groups.. In patients with seasonal allergic rhinitis, intranasal glucocorticoids are more effective than an antileukotriene drug or combined antileukotriene-antihistamine for the reduction of pollen-induced nasal eosinophilic inflammation and for control of nasal symptoms.

Topics: Acetates; Administration, Intranasal; Adult; Androstadienes; Circadian Rhythm; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Fluticasone; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Nasal Mucosa; Pollen; Quinolines; Rhinitis; Rhinitis, Allergic, Seasonal; Sulfides

Intranasal glucocorticosteroids are effective in seasonal allergic rhinitis. This study compared the efficacy of budesonide (Rhinocort Turbuhaler) and fluticasone propionate (Flixonase) in this respect.. Patients (n = 280) were randomized to receive budesonide, 140 microg (delivered dose) once daily, fluticasone, 200 microg once daily, or matching placebos for 5 weeks. The primary efficacy variable was the change in combined nasal symptom (nasal blockage, runny nose, sneezing) scores. Quality of life was measured in 121 patients by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the Short-form Health Survey (SF-36).. Both steroids significantly reduced combined nasal symptoms, compared with placebo. There was no significant difference between the two treatments. Substantial or total symptom control was achieved in 89.9% of the budesonide-treated patients, compared with 88.7% with fluticasone and 42.7% with placebo. Four of the five domains of the RQLQ were significantly improved with budesonide, whereas with fluticasone only two domains were improved. Budesonide significantly improved scores in five out of eight domains of the SF-36, whereas no domains were improved with fluticasone.. There was no significant difference in efficacy between budesonide and fluticasone in this study. However, greater improvements in quality of life were seen with budesonide than with fluticasone.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Budesonide; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome

Local antigen presentation may be necessary for both primary and recall T-cell responses to grass pollen in hay fever patients. We examined the effect of seasonal allergen exposure on nasal mucosal antigen-presenting cell (APC) populations and the effects of topical corticosteroid therapy.. Nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis patients before the grass-pollen season. A second biopsy was collected during the pollen season, when patients had received 6 weeks' treatment with either fluticasone propionate (200 microg, twice daily) or placebo. Cell populations in biopsy sections were quantified by immunocytochemistry.. Significant increases in submucosal and epithelial CD1a+ Langerhans cells, but not CD68 + macrophages or CD20 + B cells, were observed during the pollen season. Seasonal increases in CD1a+ Langerhans cells were inhibited by corticosteroid therapy.. Recruitment of CD1a+ Langerhans cells to the nasal mucosa during natural seasonal allergen exposure may contribute to local T cell responses. Topical corticosteroids may act, at least in part, by inhibiting effective allergen presentation to T cells through inhibition of recruitment of Langerhans cells to the nasal mucosa.

Topics: Administration, Topical; Adult; Androstadienes; Antigens, CD; Antigens, CD1; Antigens, CD20; Antigens, Differentiation, Myelomonocytic; Biopsy; Cell Movement; Female; Fluticasone; Humans; Immunohistochemistry; Langerhans Cells; Macrophages; Male; Nasal Mucosa; Poaceae; Pollen; Rhinitis, Allergic, Seasonal

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

Topical corticosteroid therapy reduces symptoms and nasal mucosal inflammatory cells in patients with allergic rhinitis. Usually patients are advised to start their medication (1 week) before the beginning of the pollen season. The effect of pretreatment with a topical corticosteroid on unchallenged nasal mucosa is not well documented.. The purpose of this study was to investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms and inflammatory cell numbers after nasal allergen provocation in patients with seasonal allergic rhinitis.. Nineteen patients with grass pollen-induced allergic rhinitis were treated for a 6-week period out of the grass pollen season. After completing the treatment period, patients were challenged with grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient. In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, macrophages, and Langerhans' cells were investigated.. After 4 weeks of treatment but before allergen provocation, significantly fewer epithelial Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found in the fluticasone propionate group compared with those found in the placebo group. In the lamina propria significantly fewer Langerhans' cells and eosinophils were found in the fluticasone propionate group. Cell influx in nasal mucosa after allergen provocation was significantly inhibited in the fluticasone propionate group compared with that in the placebo group for epithelial Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria eosinophils, mast cells, Langerhans' cells, macrophages, and T cells.. Fluticasone propionate is effective in reducing early- and late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells in unchallenged nasal mucosa.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Double-Blind Method; Female; Fluticasone; Humans; Immunohistochemistry; Male; Middle Aged; Nasal Mucosa; Rhinitis, Allergic, Seasonal

The daily use of either intranasal corticosteroids or histamine(1) (H(1)) receptor antagonists has proved to be efficacious in the treatment of seasonal allergic rhinitis. Most patients, however, use these medications as needed. Our objective was to compare the effectiveness of as-needed use of H(1) receptor antagonists with that of intranasal corticosteroids in the treatment of seasonal allergic rhinitis.. We performed a randomized, open-label, parallel-group study comparing the as-needed use of an H(1) receptor antagonist (loratadine) with that of an intranasal corticosteroid (fluticasone propionate) in the management of fall seasonal allergic rhinitis in the fall of 1999. Subjects kept a diary of their daily symptoms and were examined at enrollment into the study and biweekly for 4 weeks during treatment. Outcome measures were the Rhinoconjunctivitis Quality of Life Questionnaire score, daily symptom diary scores, and the number of eosinophils and the levels of eosinophilic cationic protein in nasal lavage samples.. Patients in the fluticasone-treated group reported significantly better scores in the activity, sleep, practical, nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life Questionnaire. The median total symptom score in the fluticasone-treated group was significantly lower than that in the loratadine-treated group (4.0 vs 7.0; P<.01). After treatment, the number of eosinophils was significantly smaller in the fluticasone-treated group compared with the loratadine-treated group (P =.001). Eosinophilic cationic protein levels followed the same pattern, with a significant correlation between the levels of eosinophilic cationic protein and the number of eosinophils (r(s) = 0.70, P<.01).. As-needed intranasal corticosteroids reduce allergic inflammation and are more effective than as-needed H(1) receptor antagonists in the treatment of seasonal allergic rhinitis.

Topics: Administration, Intranasal; Administration, Oral; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Eosinophils; Fluticasone; Histamine H1 Antagonists; Humans; Loratadine; Nasal Lavage Fluid; Nasal Provocation Tests; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome

The daily use of intranasal corticosteroids is approved for the treatment of seasonal allergic rhinitis.. Our objective was to test the effectiveness of as-needed use of intranasal corticosteroids in the treatment of seasonal allergic rhinitis.. A double-blind, placebo-controlled, randomized, parallel-group study of the as-needed usage of fluticasone propionate nasal spray in the management of seasonal allergic rhinitis was performed. Outcome measures were symptom score, Rhinitis Quality of Life Questionnaire (RQLQ), and the number of eosinophils and the level of eosinophilic cationic protein (ECP) in nasal lavage.. Twenty-six subjects in each group completed the 4-week study. The median symptom score over the duration of the study in the placebo group was 8.5 versus 4.5 in the active group. The active group had significant improvement on the interim visit in the sleep, non-nose/eye, activities, nasal, practical, and overall domains (P <.05) of the RQLQ and on the final visit in the nasal symptom domain. The number of eosinophils was significantly lower in the active than in the placebo group at the final visit. Changes in ECP were not significant.. As-needed fluticasone propionate nasal spray is efficacious in the treatment of seasonal allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Blood Proteins; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Nasal Mucosa; Quality of Life; Rhinitis, Allergic, Seasonal; Ribonucleases; Surveys and Questionnaires; Time Factors

It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.. In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.. In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.. Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Compliance; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.. This single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFNgamma, RANTES and TNFalpha) were counted in the biopsies.. Preventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL-5 and IL-6. After allergen provocation, levels of most of the measured cytokines (IL-3, IL-5, IL-6, IL-13, IFNgamma, RANTES and TNFalpha) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL-3, IL-6 and IL-8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL-3, IL-10 and IL-13).. These results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Cytokines; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Seasonal; RNA, Messenger

The authors have recently demonstrated that prior exposure for 6 h to 400 p.p.b. nitrogen dioxide significantly enhances the early phase response of eosinophils in the nasal airways of allergic rhinitics to subsequent allergen provocation.. To investigate whether treatment with fluticasone propionate aqueous nasal spray (FP) can alter the inflammatory response in the nasal airways under these conditions.. Sixteen allergic, rhinitic patients were recruited for this double-blind, randomized, cross-over study and received either topical FP 200 microg once daily or matched placebo for 4 weeks. At the end of treatment, all underwent nasal lavage followed by a 6 h exposure to 400 p.p.b. NO2. Following exposure to NO2, nasal allergen challenge was performed and nasal lavage repeated. After a 4 week washout period, patients were given alternate treatment and tested as above.. Analysis of eosinophil cationic protein (ECP) in lavage samples from patients treated with placebo, demonstrated that this was significantly increased from a median value of 2.3 ng/mL (range: 1.0-7.1) to 15.1 ng/mL (range: 1.5-40.0; P = 0.001) following exposure to NO2 and allergen challenge. However, in patients treated with FP, ECP concentrations only increased from 3.3 ng/mL (range: 0.2-9.2) to 5.1 ng/mL (range: 0.3-20.0; P = 0.034) following exposure to NO2 and allergen challenge. The difference of the changes in ECP concentration between the placebo and the FP-treated group was significant (P = 0.003). Similarly, there was a significant increase in the number of eosinophils in nasal lavage after exposure to NO2 and allergen challenge in the placebo group, and this increase was inhibited in FP group (P = 0.002).. These results suggest that FP influences NO2- and allergen-induced changes in eosinophil function, as well as eosinophil number in the nasal airway of allergic rhinitics.

Topics: Adult; Allergens; Androstadienes; Anti-Allergic Agents; Blood Proteins; Cross-Over Studies; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Humans; Inflammation Mediators; Male; Middle Aged; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Nebulizers and Vaporizers; Nitrogen Dioxide; Rhinitis, Allergic, Seasonal; Ribonucleases

Treatment options for allergic rhinitis include antihistamines, decongestants, anticholinergics, cromolyn sodium and corticosteroids. As the nose is a small organ, comprising less than 1% of total body mass and surface area, it seems logical to confine treatment of rhinitis to the diseased organ.. To evaluate the effects of therapy with intranasal fluticasone propionate (FP), both on subjective symptoms and pathophysiological mechanisms, in rhinitis patients during pollen season when the patients were symptomatic.. We used a double-blind, placebo (PLA)-controlled, randomized, double dummy, parallel group study of the effect of 6 weeks treatment. The double-blind comparison was made between the following three treatments: FP aqueous nasal spray, 200 microg taken once daily, levocabastine (LEV) nasal spray, 200 microg taken twice daily and PLA nasal spray. Clinical evaluation and the levels of cells and mediators in nasal washing were performed before and after treatments. Twenty-four patients (11 men and 13 women, aged 17-50 years, mean age 30.1 +/- 8.5) with strictly seasonal allergic rhinitis to Parietaria entered the study. Clinical evaluation and the levels of inflammatory cells (eosinophils and activated eosinophils, i.e. EG2+) and their mediators (tryptase, eosinophil cationic protein, eosinophil protein X and neutrophil myeloperoxidase) in nasal-lavage were performed before and after treatments.. Treatment with FP significantly increased, with respect to placebo, the percentage of days without sneezing (P < 0. 001), nasal blockage (P < 0.001), rhinorrhea (P < 0.001), nasal itching (P < 0.001). Furthermore, treatment with FP showed additional benefits with respect to LEV. The percentage of days without nasal blockage was significantly higher in the FP group that in the placebo group (P = 0.018). The same applied to rhinorrhea (P = 0.009). The percentages of days without sneezing and itching were instead not significantly different between the two groups. As expected, no significant differences were observed in baseline medians of the rhinitis symptom scores as well as in mean values of all mediators and eosinophils in nasal lavages of the various groups under study. After treatment the mean of subjective symptoms as well as all values in nasal lavage level fell significantly only in the FP group, whereas no significant changes were observed either in LEV or PLA groups. Accordingly, significant differences were observed at the end of the treatments between the values of fluticasone group vs LEV and PLA group values. Significant correlations between these values and symptom scores were found, according with literature data suggesting a pathogenetic role for these mediators and eosinophils in rhinitis.. FP (200 microg once daily) affords a significant degree of improvement in rhinitis control during pollen season, as measured by subjective and objective parameters, compared with LEV (200 microg twice daily) and PLA. The therapeutic benefits of intranasal FP are reflected in, and may be caused by, the decrease in nasal inflammatory cells.

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Piperidines; Pollen; Rhinitis, Allergic, Seasonal

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Eosinophilia; Female; Fluticasone; Histamine H1 Antagonists; Humans; Hydrocortisone; Male; Piperidines; Rhinitis, Allergic, Seasonal

Nasal allergen provocation has demonstrated that allergen-induced rhinitis is associated with an increase in local IL-4 mRNA and IgE heavy chain (Cepsilon) and IgE heavy chain promoter (Iepsilon) RNA and that pretreatment with topical glucocorticosteroids inhibits the increase in these transcripts.. This study was undertaken to determine whether observations made after acute allergen provocation can be extended to the case of chronic exposure experienced during the pollen season.. Biopsy specimens were obtained from the inferior turbinate of 33 pollen-sensitive subjects with allergic rhinitis before and during pollen season. Patients were randomized in a double-blind fashion and treated with either topical steroids (200 microg fluticasone propionate twice daily; n = 16) or matched placebo nasal spray (n = 17) before the pollen season. Alkaline phosphatase anti-alkaline phosphatase immunocytochemistry was used to identify B cells (CD20+), and in situ hybridization was used to detect IL-4, Cepsilon, and Iepsilon RNA+ cells.. Baseline examination revealed IL-4 and Cepsilon RNA but virtually no Iepsilon RNA+ cells in the nasal mucosa. Analysis revealed a significant difference in the expression of Cepsilon and Iepsilon RNA+ cells (p < 0.001). Biopsy specimens taken after antigen exposure exhibited highly significant increases in placebo-treated (p < 0.001) but not steroid-treated patients. In both groups, the number of CD20+ cells was unchanged when preexposure and postexposure biopsy specimens were compared.. These results show strong support for the hypothesis that IgE class switching occurs locally within the nasal mucosa of subjects with seasonal allergic rhinitis and that this response can be inhibited through strategies directed against local IgE production.

Topics: Administration, Intranasal; Alkaline Phosphatase; Androstadienes; Anti-Inflammatory Agents; Antigens, CD20; B-Lymphocytes; DNA, Complementary; Double-Blind Method; Fluticasone; Gene Expression; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Glucocorticoids; Humans; Immunoglobulin E; Immunoglobulin G; Immunoglobulin Heavy Chains; Immunohistochemistry; In Situ Hybridization; Interleukin-4; Nasal Mucosa; Pollen; Rhinitis, Allergic, Seasonal; RNA Probes; Seasons

Allergen specific nasal challenge (ASNC) is an optimal method to study the pathophysiological mechanisms sustaining the allergic inflammation and in particular the adhesion molecule system, which is involved in cellular infiltration of nasal mucosa. Topical steroids have been accepted as a highly effective anti-inflammatory therapy for allergic rhinitis.. The aim of this double-blind placebo- controlled study was the evaluation of clinical and cytological parameters, including ICAM-1 expression on nasal epithelial cells, after a 4 week treatment with nasal fluticasone propionate (200 microg/daily) or placebo, using the model of ASNC.. Twenty allergic rhinitics underwent nasal challenge before and after treatment. The following parameters were evaluated: (i) nasal symptoms (rhinorrhoea, itching, sneezing, obstruction), (ii) inflammatory cells (eosinophils and neutrophils), (iii) ICAM-1 expression on nasal epithelial cells at baseline, 30 min (early phase) and 6 h (late phase) after ASNC.. Fluticasone propionate was capable of reducing: (i) clinical symptoms during both early (P<0.001) and late phase (P<0.04), (ii) eosinophil (P<0.002) and neutrophil (P<0.001) infiltrate during late phase, and (iii) ICAM-1 expression on nasal epithelial cells during both early (P < 0.01) and late phase (P < 0.03).. The present results demonstrate that fluticasone propionate exerts a significant action on early and late phase clinical events following specific nasal challenge, reducing also the cellular influx during the late phase. This event is likely due to the modulation of ICAM-1 expression on epithelial cells.

Topics: Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Eosinophils; Epithelial Cells; Female; Fluticasone; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Male; Middle Aged; Nasal Mucosa; Neutrophils; Rhinitis, Allergic, Seasonal

We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 microg, once daily) and matching placebo. NACs were performed before and at 6 h and 1, 2, 3, and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS, both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils: P=0.032; ECP: P=0.038). The onset became even more important at day 7 (eosinophils: P=0.001; ECP: P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (P=0.017) and for sneezing at day 7 (P=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Blood Proteins; Cross-Over Studies; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Humans; Inflammation Mediators; Male; Rhinitis, Allergic, Seasonal; Ribonucleases

The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon.. Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls.. During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001).. Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.

Topics: Acute-Phase Proteins; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Biomarkers; Blood Cell Count; Blood Proteins; Carrier Proteins; Double-Blind Method; Eosinophil Granule Proteins; Eosinophil Peroxidase; Eosinophils; Female; Fluticasone; Histamine H1 Antagonists; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Nasal Lavage Fluid; Oncogene Proteins; Peroxidases; Proto-Oncogene Proteins; Rhinitis, Allergic, Seasonal; Ribonucleases; Seasons; Treatment Outcome

Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas.. Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study.. Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Pollen; Quality of Life; Rhinitis, Allergic, Seasonal; Texas

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

Nasal allergen provocation in patients with allergic rhinitis leads to expression of the proeosinophilic cytokines IL-5 and GM-CSF and tissue eosinophilia.. We sought to examine the effect of natural seasonal allergen exposure on IL-5 and GM-CSF mRNA expression and nasal eosinophilia and to evaluate the effects of topical corticosteroid therapy on these responses.. Nasal biopsy specimens were collected from 46 grass pollen-sensitive patients with seasonal rhinitis before the grass pollen season. A second biopsy specimen was collected during the pollen season, by which time patients had received 6 weeks treatment with either fluticasone propionate (200 micro(g) twice daily) or placebo nasal spray.. Fluticasone treatment was clinically effective (P <.005). Patients receiving placebo, but not fluticasone, showed increased numbers of epithelial and submucosal EG2+ eosinophils (P <.005) and IL-5 and GM-CSF mRNA-expressing cells (P <.0001) during the pollen season. Colocalization experiments showed that greater than 80% of IL-5 mRNA-expressing cells were submucosal CD3+ T cells in both groups. The numbers of submucosal CD3+ T cells did not increase during the pollen season or decrease with fluticasone treatment. Fluticasone also inhibited IL-5 secretion by grass pollen-stimulated peripheral blood T cells from patients with seasonal rhinitis (n = 5, inhibitory concentration of 50% = 10(-9) to 10(-10) mol/L).. These results suggest that topical corticosteroids may reduce eosinophilia in seasonal rhinitis by inhibiting T cell IL-5 production.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Biopsy; CD3 Complex; Cells, Cultured; Eosinophilia; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; In Situ Hybridization; Interleukin-5; Nasal Mucosa; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; RNA, Messenger; Skin Tests; T-Lymphocytes

Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid.. Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF.. Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF.. The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Antisense Elements (Genetics); Biopsy; Eosinophilia; Epithelium; Female; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immune System; Immunohistochemistry; Immunophenotyping; In Situ Hybridization; Male; Nasal Mucosa; Placebos; Rhinitis, Allergic, Seasonal; RNA Probes; RNA, Messenger; Time Factors; Up-Regulation

To determine whether better health-related quality of life (HRQL) is achieved by initiating treatment of seasonal (ragweed) rhinoconjunctivitis (hay fever) with a nasal steroid (fluticasone) backed up by a nonsedating antihistamine (terfenadine) or whether it is better to start with the antihistamine and add the nasal steroid when necessary.. Randomized, nonblind, parallel-group management study during the 6 weeks of the ragweed pollen season in 1995.. Sixty-one adults with ragweed pollen hay fever recruited from patients who had participated in previous clinical studies and from those who responded to notices in the local media.. Southern Ontario.. Nasal steroid group: 200 micrograms of fluticasone nasal spray when needed (up to 400 micrograms/d) starting about 1 week before the ragweed pollen season and continued throughout, with 1 to 2 tablets of terfenadine daily (maximum 120 mg/d) if needed. Antihistamine group: 1 60-mg tablet of terfenadine when needed (maximum 120 mg/d) starting about 1 week before the ragweed pollen season and continued throughout, with 200-400 micrograms/d of fluticasone nasal spray (maximum 400 micrograms/d) if needed.. HRQL before, at the height of and toward the end of the ragweed pollen season; HRQL was measured using the Rhinoconjunctivitis Quality of Life Questionnáire.. Overall, HRQL tended to be better in the group of patients whose first-line treatment was with fluticasone (p = 0.052), but the difference between the 2 groups was small and not clinically important. Just over half (52% [16/31]) of the patients in the fluticasone group did not need additional help with terfenadine, whereas only 13% (4/30) of those in the terfenadine group did not need additional help with fluticasone (p = 0.002).. There is little difference in the therapeutic benefit between the 2 approaches for the treatment of ragweed pollen hay fever. Therefore, the approach to treatment should be based on patient preference, convenience and cost. Regardless of the treatment, at least 50% of patients will need to take both types of medication in combination to control symptoms adequately.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Allergic Agents; Conjunctivitis; Female; Fluticasone; Histamine H1 Antagonists; Humans; Male; Quality of Life; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome

The effectiveness and safety of fluticasone propionate aqueous nasal spray (200 micrograms once daily for 4 weeks) were compared with those of loratadine (10 mg once daily for 4 weeks) in 114 adults and adolescents with seasonal allergic rhinitis in this multicenter, double-blind, double-dummy, randomized, parallel-group study. Patients recorded their nasal symptoms (nighttime and daytime obstruction, sneezing, itching, rhinorrhea, and overall discomfort) using a 4-point scale (0 = no symptoms, 3 = very frequent symptoms) in daily diaries. Clinicians assessed patients' nasal symptoms (nighttime and daytime obstruction, sneezing, itching, and rhinorrhea) using a 4-point scale at every scheduled visit. Clinicians and patients assessed the overall effectiveness of treatment at the end of the study. Fluticasone propionate improved clinician-rated total nasal symptom scores (defined as the sum of five nasal symptoms) more than loratadine at the 2-week and 4-week assessments (P < or = 0.008). Clinicians give fluticasone propionate better global ratings than loratadine (P = 0.04). After 4 weeks of treatment, between-group differences in clinician-rated individual nasal symptoms favored fluticasone propionate (P < 0.05), with the exception of nasal itching (P = 0.11). These findings were confirmed by between-group differences in the percentages of symptom-free days calculated from patient-recorded daily diary-card data. Both treatments were well tolerated. The incidence of adverse events between groups was similar. Fluticasone propionate aqueous nasal spray 200 micrograms administered once daily in the morning was more effective than loratadine 10 mg administered once daily for the treatment of seasonal allergic rhinitis.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Female; Fluticasone; Humans; Loratadine; Male; Middle Aged; Rhinitis, Allergic, Seasonal

The allergen-induced late nasal response (LNR) is associated with high expression of interleukin-4 (IL-4) and IL-5 messenger RNA (mRNA) in the nasal mucosa, suggesting a role for Th2-type cytokines in the development of the LNR. Moreover, topical corticosteroid-mediated inhibition of the LNR is accompanied by inhibition of IL-4, but not IL-5, mRNA expression, IL-13 shares a number of functions with IL-4, including IgE switching and vascular cell adhesion molecule-1 (VCAM-1) upregulation. We investigated the expression of IL-13 mRNA and immunoreactivity in nasal biopsies from 10 normal subjects and 20 subjects with allergic rhinitis. IL-4 mRNA expression was examined in the same subjects. The allergic rhinitis patients were randomized to receive a 6-wk treatment with either topical fluticasone propionate (n = 10) or placebo (n = 10) nasal spray twice daily. A nasal biopsy was taken before treatment and 24 h after local nasal allergen provocation with a grass-pollen extract. Before treatment, there was no significant difference between the allergic rhinitis patients and controls in the expression of IL-13 mRNA and immunoreactivity. After allergen provocation, we observed a significant increase in IL-13 mRNA-positive and immunoreactive cells at 24 h only in subjects given placebo (P < 0.001). Inhibition of the LNR after corticosteroid treatment was associated with a marked decrease in allergen-induced IL-13 mRNA-positive (P < 0.001) and immunoreactive cells (P < 0.001). In subjects given placebo, 76.9 +/- 5.5% of IL-13 mRNA-positive cells observed after allergen were CD3+, whereas 11.2 +/- 2.7% coexpressed immunoreactivity for mast-cell tryptase. In these subjects, increases in cells expressing IL-13 mRNA were greater than for IL-4 mRNA (P = 0.001), and double in situ hybridization studies revealed that 100% of the IL-4 mRNA-positive cells coexpressed IL-13 mRNA, whereas 66.6 +/- 10.5% of IL-13 mRNA-positive cells coexpressed IL-4 transcripts after allergen challenge. The results of this study suggest that IL-13 expression is a prominent feature of the LNR, and that inhibition of the LNR following steroid therapy may be partly attributable to inhibition of IL-13 expression.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Biopsy; CD3 Complex; Chymases; Female; Fluticasone; Glucocorticoids; Humans; Interleukin-13; Interleukin-4; Male; Mast Cells; Nasal Mucosa; Placebos; Reference Values; Rhinitis, Allergic, Seasonal; RNA, Messenger; Serine Endopeptidases; Transcription, Genetic; Tryptases

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Drug Therapy, Combination; Fluticasone; Humans; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Rhinitis, Allergic, Seasonal; Terfenadine

Many nasal corticosteroids with different potencies and formulations are available, but they have all been proven safe and effective. The clinical relevance, if any, of these differences is not yet completely established.. We sought to compare the efficacy, safety, and patients' acceptance of triamcinolone acetonide aerosol spray and fluticasone propionate aqueous solution in the treatment of spring allergic rhinitis.. After a drug-free baseline evaluation, patients with rhinitis were randomized to receive either a triamcinolone aerosol spray of 110 microg in each nostril once daily (n = 117) or a fluticasone solution spray of 100 microg in each nostril once daily (n = 116) in a single-blind, parallel-group study. The Rhinitis Index Score (sum of scores of symptoms on a scale from 0 to 3) was evaluated daily, in the morning before drug administration, for 21 days. The efficacy of each treatment was assessed by the mean reduction from baseline in the Rhinitis Index Score and in individual symptom scores. Patients' acceptance of the study drugs was also monitored by a daily questionnaire.. Reductions of the Rhinitis Index Score (mean +/- SEM) were 4.20 +/- 0.21 and 4.60 +/- 0.21 for triamcinolone and fluticasone, respectively (p = 0.23). There were no statistically significant differences between the drugs in the reduction of any of the individual symptoms. Patients expressed statistically significant differences between the drugs regarding acceptance; different properties of the aerosol and the solution were appreciated differently.. This study shows that triamcinolone acetonide aerosol and fluticasone propionate solution sprays are both clinically equally effective, safe, and well tolerated for the treatment of spring pollen allergic rhinitis.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Female; Fluticasone; Humans; Male; Middle Aged; Patient Compliance; Rhinitis, Allergic, Seasonal; Triamcinolone Acetonide

We have studied the expression of the gene encoding the epsilon heavy chain of IgE in nasal B cells of hayfever patients. We developed probes to detect transcripts of the epsilon germ-line gene and the rearranged gene by in situ hybridization of biopsy sections from the nasal mucosa. We compared tissue from hayfever patients out of season with that of normal controls, and also of hayfever patients treated with topical corticosteroid (fluticasone propionate) or placebo for 6 weeks and then challenged with antigen. epsilon chain mRNA was expressed in an unexpectedly high proportion of nasal B cells of both hayfever patients and normal subjects. However, although similar numbers of B cells were found in both groups, the proportion of cells that express epsilon chain mRNA was several times higher in the hayfever patients. No transcripts of the epsilon germ-line gene were detected in either group before allergen challenge. When hayfever patients were administered antigen locally, early (10-30 min) and late (1-24 h) symptoms ensued. After 24 h, coincident with an increase in the number of cells expressing mRNA for IL-4 in the tissue, epsilon germ-line gene transcripts appeared in the nasal B cells. The induction by allergen of IL-4 mRNA and epsilon germ-line gene transcripts was suppressed by fluticasone propionate treatment. Our results suggest that local IgE synthesis and cytokine regulation of heavy chain switching to IgE occur in the nasal mucosa.

Topics: Administration, Topical; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; B-Lymphocytes; Female; Fluticasone; Gene Expression Regulation; Genes, Immunoglobulin; Glucocorticoids; Humans; Immunoglobulin Constant Regions; Immunoglobulin E; Immunoglobulin epsilon-Chains; Interleukin-4; Male; Nasal Mucosa; Rhinitis, Allergic, Seasonal; RNA, Messenger; Transcription, Genetic

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Topics: Administration, Intranasal; Adolescent; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Fluticasone; Headache; Humans; Loratadine; Male; Nose; Pharyngitis; Pulmonary Ventilation; Rhinitis, Allergic, Seasonal; Treatment Outcome

Comparative studies with topical corticosteroids and antihistamines for treatment of allergic rhinitis have not always demonstrated clear distinctions between the two on the basis of therapeutic efficacy.. This study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray with those of terfenadine in the treatment of seasonal allergic rhinitis.. Three hundred forty-eight patients with allergic rhinitis were given fluticasone propionate aqueous nasal spray (200 micrograms once daily), terfenadine tablets (60 mg twice daily), or placebo for 4 weeks in a multicenter, randomized, double-blind, double-dummy, parallel-group study.. Clinician-rated total nasal symptom scores after 1, 2, 3, and 4 weeks of therapy and patient-rated total nasal symptom scores throughout treatment were significantly (p <0.05) lower in the fluticasone propionate group compared with the terfenadine group or the placebo group. Terfenadine was not statistically different from placebo on the basis of clinician-related nasal symptom scores, except for sneezing. Total nasal airflow, measured by rhinomanometry, significantly (p <0.05) improved in the fluticasone propionate group compared with the terfenadine group or the placebo group. More fluticasone propionate-treated patients compared with placebo-treated patients had reduced nasal mucosal eosinophil counts after 4 weeks of therapy (p <0.05). No serious or unusual drug-related adverse events were reported. Morning plasma cortisol concentrations after 4 weeks of therapy did not differ among groups.. Fluticasone propionate aqueous nasal spray is more effective than terfenadine tablets for treatment of seasonal allergic rhinitis.

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

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

Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis.. We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season.. We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended.. Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups.. The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Drug Administration Schedule; Eosinophil Granule Proteins; Eosinophilia; Female; Fluticasone; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nasal Lavage Fluid; Pollen; Rhinitis, Allergic, Seasonal; Ribonucleases; Seasons

It is well known that an initial treatment with several kinds of antiallergic medicines is useful for patients suffering from Japanese cedar pollinosis to reduce nasal symptoms during the pollen season. Also topical corticosteroids show a preventive effect as antiallergic medicines. In this study, the preventive effect of topical corticosteroids with antiallergic medicine as an initial treatment was evaluated during the 1995 cedar pollen season a season in which a high pollen count was anticipated. Twenty-five patients with cedar pollinosis were selected and divided into two groups. A and B, A topical corticosteroid (fluticasone propionate; Flunase) as well as antiallergic medicine (azelastin) were administered to patients in group A 4 weeks before the beginning of the pollen season. In group B, only antiallergic medicine was given at the same time as group A and a topical corticosteroid was administered after the appearance of the symptoms. Nasal symptoms and mucosal conditions of the nasal cavity were monitored throughout the pollen season. The inflammatory cells in the mucoepithelial layer of the nasal mucosa were also periodically evaluated by immunohistochemical staining. Nasal symptoms and mucosal conditions in group A were significantly improved compared with patients in group B. The infiltration of macrophages in the mucoepithelial layer of the nasal mucosa was strongly inhibited in group A. The numbers of mast cells and EG2-positive cells in group A were not significantly different from those in group B during the pollen season. According to these results, although not all inflammatory cells were inhibited, the initial treatment with Flunase aqueous nasal spray in addition to the conventional initial treatment with antiallergic medicine is very useful for reducing symptoms even in a season with a large amount of cedar pollen.

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Allergens; Androstadienes; Anti-Allergic Agents; Female; Fluticasone; Humans; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal; Seasons; Trees

Allergen-induced nasal responses are associated with the recovery of proinflammatory mediators and cytokines. In recent years, a distinct group of chemotactic cytokines, chemokines, has been the focus of intense investigation as to their possible role in the pathogenesis of allergic diseases. Although corticosteroids have been known to be effective in the treatment of allergic diseases, their mechanism(s) of action has not been fully elucidated.. To study the effect of topical fluticasone on the recovery of chemokines (IL-8, MIP-1 alpha, and RANTES) and other cytokines (IL-1 beta, IL-6, and GM-CSF) from nasal mucosa following allergen challenge. To correlate the improvement of rhinitis symptoms with cytokine levels during early-phase and late-phase allergic responses.. A randomized, double-blind, placebo-controlled crossover study of fluticasone propionate, 200 micrograms q d, was performed in ten subjects with allergic rhinitis. Allergen challenge was administered after 1 week of treatment. Nasal secretions were collected immediately after challenge and during the late-phase reactions; symptom scores were recorded simultaneously. Nasal cytokines were assayed by specific ELISA.. The allergen challenge caused early-phase and late-phase allergic reactions and increased recovery of IL-1 beta, IL-6, IL-8, RANTES, MIP-1 alpha, and GM-CSF from the nasal mucosa. Intranasal fluticasone inhibited the allergen-induced increase in nasal symptoms. This was associated with decreases in cytokine recovery. A significant correlation was observed between decreases in cytokine levels and in symptom scores after treatment.. Our results suggest that treatment with topical fluticasone propionate inhibits allergen-induced nasal responses and the associated increase in the production/secretion of chemokines and other proinflammatory cytokines.

Topics: Administration, Topical; Allergens; Androstadienes; Animals; Anti-Inflammatory Agents; Chemokines; Cross-Over Studies; Cytokines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Fluticasone; Glucocorticoids; Humans; Mites; Nasal Mucosa; Nasal Provocation Tests; Pollen; Rhinitis, Allergic, Seasonal

Eighty five patients with seasonal allergic rhinitis, currently symptomatic, were treated with fluticasone proportionate nasal spray (Flixonase) in open, multicentre efficacy and safety study. The drug studied statistically significant decrease all but one (conjunctivitis) symptoms of the disease in the first week of treatment in the patient's and doctor's assessment. The full effect of treatment was revealed in the second week. There was significant protective effect observed during two weeks after the cessation of treatment. Adverse events were mild and occurred in two cases, due to disease itself rather, than the drug tested.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Asthmatic Agents; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal; Treatment Outcome

Fluticasone propionate aqueous nasal spray (FPANS) contains fluticasone propionate, which is a new topically active glucocorticoid with approximately twice the potency of belcomethasone dipropionate. In this European multicentre study, 143 children with seasonal allergic rhinitis were recruited: 47 received FPANS 100 micrograms once a day (od), 46 received FPANS 200 micrograms od, and 50 patients received placebo od, for 4 weeks. Treatment efficacy was assessed using diary card nasal symptom scores for sneezing, rhinorrhoea, blockage and itching, and eye watering/irritation. Patients receiving FPANS 100 micrograms or FPANS 200 micrograms demonstrated statistically significant improvements in median nasal symptom scores in all the symptoms recorded, when compared with placebo. There were no statistically significant differences between the FPANS 100 micrograms and FPANS 200 micrograms groups in improvement in nasal symptom scores. There was no effect on eye watering/irritation symptoms which could be attributed to either FPANS 100 micrograms or FPANS 200 micrograms when compared with placebo. Use of rescue antihistamine medication was significantly reduced in the FPANS 100 micrograms group when compared with placebo. The adverse events profile was similar in all three treatment groups, and the events reported were generally mild and related to the patients' rhinitis.

Topics: Administration, Inhalation; Androstadienes; Anti-Allergic Agents; Child; Double-Blind Method; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal; Solutions; Treatment Outcome

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

Seasonal allergic rhinitis is characterized by the development of nasal mucosal inflammation in response to natural allergen exposure, and is prevented by the administration of topical corticosteroids. Interleukin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is inhibited by corticosteroids. In this study we have therefore investigated the effect of seasonal allergen exposure on the expression of immunoreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular prophylactic treatment with the topical corticosteroid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treatment during the pollen season with either topical fluticasone nasal spray (200 micrograms daily) or matching placebo. Each subject underwent a repeat nasal biopsy at the end of the 6-wk treatment period. Seasonal increases in epithelial eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial mast cells (p = 0.055) occurred in the placebo--but not the fluticasone-treated patients. Submucosal mast cell numbers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in both mast cells and eosinophils. Numbers of IL-4+ cells in the nasal submucosa were significantly suppressed by treatment with fluticasone (p = 0.0003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL-5 and IL-6 immunoreactive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Immunohistochemistry; Interleukin-4; Interleukin-5; Interleukin-6; Interleukins; Male; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Seasonal

This multicentre, randomized, double-blind, parallel-group study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray 200 micrograms once daily (FPANS 200 micrograms od) with FPANS 200 micrograms twice daily (bd) in patients whose seasonal rhinitis symptoms were not completely controlled with FPANS 200 micrograms od. A total of 549 patients initially received FPANS 200 micrograms od during the open-treatment phase of the study. After 2 weeks, 65% of patients had their symptoms well controlled by FPANS 200 micrograms od and continued with this treatment for a further 2 weeks. The remainder received either FPANS 200 micrograms od or FPANS 200 micrograms bd for a further 2 weeks. Efficacy was evaluated by the analysis of symptom-free days. In the uncontrolled group, there was a significant increase in the percentage of symptom-free days in the FPANS 200 micrograms bd group over the FPANS 200 micrograms od group for nasal blockage on waking (P < 0.05) and nasal blockage during the day (P < 0.05). Similar trends were observed for sneezing, rhinorrhoea, nasal itching, and eye symptoms. There was a significant increase in the percentage of days with a symptom score of less than 2 in FPANS 200 micrograms bd group for nasal blockage during the day (P < 0.05). Adverse events were similar in nature and frequency in each treatment group. It is concluded that in the majority of patients symptoms of seasonal rhinitis are well controlled by FPANS 200 micrograms od. In the minority of patients whose symptoms are not adequately controlled by a once daily dose, FPANS 200 micrograms bd provides additional relief, particularly from nasal blockage.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Double-Blind Method; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal

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

We have examined the effect of prolonged treatment with topical corticosteroid on allergen-induced early and late nasal responses and the associated inflammatory cell infiltrate in grass pollen sensitive allergic rhinitics. Following a randomized double-blind 6 week treatment period with fluticasone propionate 200 micrograms aqueous nasal spray twice daily or matched placebo spray, nasal provocation was performed using Timothy grass pollen extract. Nasal symptoms were recorded at intervals from 0 to 24 h. Nasal biopsies were performed before treatment and at 24 h after allergen and processed for immunohistology. When corticosteroid-treated patients were compared with the placebo group there was an approximately 50% decrease in the size of the early (0-60 min) response and almost complete inhibition of late (1-24 h) nasal symptoms after allergen challenge. After allergen challenge markedly fewer T lymphocytes and CD25+ (interleukin-2 receptor bearing) cells were observed in both the epithelium and submucosa in fluticasone treated patients compared with the placebo group. Significantly less total and activated eosinophils were observed, particularly within the nasal epithelium. Submucosal mast cell counts were decreased, whereas increased numbers of submucosal neutrophils were observed. These results confirm that topical corticosteroid treatment inhibits allergen-induced early and late nasal responses. This may possibly occur following a decrease in T lymphocytes and/or mast cells and their products and a consequent reduction in tissue eosinophilia.

Topics: Administration, Topical; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Cell Count; Chemotaxis, Leukocyte; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Immunoenzyme Techniques; Male; Nasal Mucosa; Nasal Provocation Tests; Pollen; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal

Fluticasone Propionate Aqueous Nasal Spray (FPANS) contains a topically active glucocorticoid fluticasone propionate which has been used successfully for the treatment of seasonal allergic rhinitis. This multicentre, randomized, double-blind, double-dummy, placebo-controlled, parallel group study was designed to compare the efficacy and tolerability of FPANS with terfenadine tablets or placebo in controlling the symptoms of allergic rhinitis to grass pollen. Two hundred and fourteen patients were treated for 6 weeks during the grass pollen season with either FPANS 200 micrograms once daily, terfenadine tablets (60 mg) twice daily or placebo. Efficacy was evaluated by the analysis of symptom-free days and median symptom scores. Patients receiving FPANS had significantly more days free of nasal blockage on waking (P = 0.012) and during the day (P = 0.01) and of rhinorrhoea (P = 0.027) than those receiving terfenadine. Additionally, in terms of absolute efficacy, patients receiving FPANS demonstrated significantly more days free of the above symptoms (P = 0.017, P = 0.028, P = 0.004, respectively) and of sneezing (P < 0.001) than those receiving placebo. There were no significant differences in symptoms of nasal itching, eye symptoms, of symptoms of drowsiness between the three treatment groups. Patients in the FPANS group had significantly lower median symptom scores for nasal blockage on waking (P < 0.001) and during the day (P < 0.018) than those in the terfenadine group and significantly lower scores for nasal blockage on waking (P < 0.001), sneezing (P < 0.013) and rhinorrhoea (P = 0.005) than those in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Adolescent; Adult; Aged; Allergens; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Tolerance; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nasal Mucosa; Nebulizers and Vaporizers; Pollen; Rhinitis, Allergic, Seasonal; Tablets; Terfenadine

The aim of the study was to investigate the effect of short-term treatment with fluticasone propionate on the response to nasal allergen challenge in patients with allergic rhinitis. Responses to nasal allergen challenge were assessed subjectively by recording symptom scores on visual analogue scales, and objectively by measuring histamine, PGD2 and LTC4 in nasal lavage and by measuring nasal inspiratory peak flow following challenge. Nasal allergen challenge resulted in an increase in all symptom scores (P < 0.05); an increase in histamine and PGD2 (P < 0.05), and a decrease in nasal inspiratory peak flow at 1 h, 5 h and 7 h following challenge (P < 0.05). The allergen-induced changes in symptom scores, mediator levels and nasal inspiratory peak flow were attenuated by treatment with fluticasone propionate (P < 0.05 for all parameters measured). Post-challenge nasal obstruction was decreased by 45%; sneezing, itching and rhinorrhoea by 73, 78 and 80% respectively in the group as a whole comparing scores whilst on fluticasone propionate with those on no therapy. Fluticasone propionate, 200 micrograms twice daily for 2 weeks is effective in reducing significantly the early and late response to nasal allergen challenge.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Female; Fluticasone; Glucocorticoids; Histamine; Humans; Inspiratory Capacity; Leukotriene C4; Male; Middle Aged; Nasal Lavage Fluid; Poaceae; Pollen; Prostaglandin D2; Radioimmunoassay; Rhinitis, Allergic, Seasonal

Allergen-induced late nasal responses are associated with recruitment and activation of T lymphocytes and eosinophils and preferential mRNA expression for T-helper type 2 (Th2) cytokines. We tested the hypothesis that topical corticosteroids may inhibit late responses by inhibiting cells expressing mRNA for Th2 cytokines. A randomized double-blind placebo-controlled trial of topical corticosteroid (fluticasone propionate) was performed in 48 adult grass pollen-sensitive patients. Nasal biopsies were taken at baseline and repeated 24 hr after local nasal allergen provocation following 6 weeks treatment with either fluticasone propionate 200 micrograms or placebo nasal spray twice daily. Baseline mRNA expression for interleukin-4 (IL-4) (P = 0.01) and IL-5 (P = 0.002) was higher in the patients than in normal controls. Topical corticosteroid treatment significantly inhibited immediate nasal symptoms, with almost complete inhibition of the late response following allergen challenge. This was associated with a marked decrease in the allergen-induced increases in cells expressing mRNA for IL-4 (P = 0.002) but not for IL-5. Inhibition of the late response was also accompanied by decreases in CD25+ cells, presumed T lymphocytes and eosinophils. A significant correlation was observed between the decreases in IL-4 mRNA+ cells and in eosinophils after treatment (r = 0.46, P < 0.05). These results suggest that prolonged treatment with topical corticosteroid inhibits allergen-induced early and late nasal responses and the associated tissue eosinophilia, and that, at least in part, this may result from inhibition of cells expressing mRNA for IL-4.

Topics: Administration, Topical; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Cytokines; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; In Situ Hybridization; Interleukin-4; Male; Middle Aged; Nasal Mucosa; Pollen; Rhinitis, Allergic, Seasonal; RNA, Messenger

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

To evaluate the efficacy and tolerability of intranasally administered fluticasone propionate, 200 micrograms or 100 micrograms (half the adult dosage) when administered once daily for 4 weeks to children with seasonal allergic rhinitis.. Double-blind, randomized, placebo-controlled, parallel-group clinical study in 10 pediatric outpatient centers.. Children (n = 249), 4 to 11 years of age, with moderate to severe symptoms of seasonal allergic rhinitis, positive skin test reaction to a local autumn allergen, and a history of seasonal allergic rhinitis.. Clinician- and patient-rated nasal symptom scores (obstruction, rhinorrhea, sneezing, itching), clinician-rated assessment of overall response to treatment, patient-rated nasal obstruction on awakening, and use of rescue medication. Clinicians questioned patients (or parents) regarding symptoms and adverse events. Morning plasma cortisol concentrations and 24-hour urinary excretion of cortisol and 17-ketogenic steroids were evaluated.. Intranasal fluticasone propionate, 200 micrograms or 100 micrograms once daily, was significantly more effective than placebo in the treatment of seasonal allergic rhinitis in children. Clinician- and patient-rated symptom scores indicated greater improvement in nasal symptoms, including nasal obstruction on awakening, among patients receiving intranasal fluticasone propionate. Overall response to treatment was also significantly greater in the active treatment groups. The two fluticasone propionate groups were not statistically different. Mean morning plasma cortisol concentrations and 24-hour urinary excretion of free cortisol and 17-ketogenic steroids were similar across all groups both before and after treatment.. Intranasal fluticasone propionate, 100 micrograms (half the adult dose) or 200 micrograms given once daily for 4 weeks is effective and well tolerated in children 4 to 11 years of age with seasonal allergic rhinitis.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Nasal Obstruction; Rhinitis, Allergic, Seasonal; Treatment Outcome

A 4-week multicenter, double-blind, placebo-controlled, parallel-group trial was carried out with 416 adults with ragweed allergic rhinitis to compare 200 micrograms of fluticasone propionate once daily and 100 micrograms of fluticasone propionate twice daily with placebo. Compared with placebo, both groups receiving fluticasone propionate had greater number of symptom free days (P < .01), lower median symptom scores (P < .01), and greater number of days not requiring rescue medications (P < .001). No significant differences for individual symptoms were found between the two fluticasone propionate groups except that those taking the twice daily dosage used less antihistamine (P < .01) and had greater number of days free of rescue medications (P < .05). Adverse events were comparable between the three groups. These results indicate that topical intranasal fluticasone propionate 200 micrograms once daily and 100 micrograms twice daily are both efficacious and well tolerated.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal

In a single-center, double-blind, crossover study of 90 subjects, fluticasone propionate aqueous nasal spray, 200 micrograms, once daily was compared with 200 micrograms twice daily in severe seasonal allergic rhinitis to ragweed. The mean percentage of days free of nasal itching and eye symptoms was significantly higher with twice daily fluticasone propionate (P = .004, P = .005, respectively). There were no significant differences between the two treatment groups for nasal blockage, rhinorrhea (runny nose), and sneezing. The median symptom scores for nasal itching were lower during twice daily treatment (P = .008) but there was no significant difference for the other symptoms. There were no significant differences between the groups in the use of rescue medication. Adverse events were infrequent, and similar in both groups. Most were considered unrelated to the treatment. Twice daily treatment with fluticasone propionate may be preferable for some patients with severe seasonal allergic rhinitis.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Pollen; Rhinitis, Allergic, Seasonal

Topical corticosteroids are widely regarded as the reference standard in allergic rhinitis therapy because they are well tolerated and effective against all rhinitis symptoms. We evaluated the efficacy, onset of action, and safety of two dosing regimens of the new corticosteroid fluticasone propionate compared with that of beclomethasone dipropionate in patients with moderate to severe seasonal allergic rhinitis.. In this double-blind, randomized multicenter trial, 110 adolescents and 128 adults were treated for 4 weeks with one of the following regimens: fluticasone aqueous nasal spray 100 micrograms twice daily or 200 micrograms once daily, beclomethasone aqueous nasal spray 168 micrograms twice daily, or placebo.. Patient-rated scores for nasal obstruction, rhinorrhea, and combined nasal symptoms indicated that the two fluticasone regimens were equally effective and that both were superior to beclomethasone during most of the study (P < or = .05) and to placebo throughout the study (P < or = .01). Both fluticasone regimens also demonstrated significant clinical efficacy by 24 hours after the first dose. Clinician-rated mean total nasal symptoms scores for all three active treatments were superior to placebo at most time points but were not significantly different from each other. All treatments were well tolerated, with similar incidence and type of adverse events in all treatment groups and no apparent effects on hypothalamic-pituitary-adrenal (HPA) axis function.. Fluticasone aqueous nasal spray was effective in relieving nasal symptoms in adolescents and adults with seasonal allergic rhinitis. Fluticasone administered once or twice daily was superior to beclomethasone administered twice daily in relieving nasal obstruction and rhinorrhea and in reducing nasal symptoms more quickly.

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

The study focuses on the relationship between the tissue density of mast cells, the tissue histamine levels and the levels of markers of mast cell activation after an allergen challenge of the nasal mucosa of allergic patients. The effect of 4 weeks' treatment with a topical glucocorticoid, fluticasone propionate, was studied in a double-blind, placebo-controlled study of 25 hay fever patients. Nasal biopsies were obtained before and after the treatment period for the evaluation of mast cell density and tissue histamine levels. Nasal challenges were performed at 2-week intervals for 8 weeks using a standardized nasal lavage model. TAME-esterase was analysed in the returned lavage fluid from all the challenges (weeks 0-8), while the levels of histamine and tryptase were analysed in lavage fluids from challenges performed before and after the treatment period (weeks 0 and 4). The symptoms of nasal allergy were assessed after each challenge. Treatment with fluticasone propionate did not influence mast cell density, the tissue histamine concentration, the lavage histamine levels or the TAME-esterase activity, while a reduction in nasal symptoms and tryptase in nasal lavage fluid was revealed. Our present study again emphasizes the fact that the mast cell is an important trigger cell in the immediate nasal allergic response. The study also demonstrates the usefulness of the measurements of tryptase as an indicator of both mast cell activation and the efficacy of topical steroid treatment.

Topics: Administration, Topical; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Histamine Release; Humans; Male; Mast Cells; Middle Aged; Nasal Mucosa; Rhinitis, Allergic, Seasonal

Fluticasone propionate aqueous spray, a new intranasal corticosteroid preparation, and disodium cromoglycate 2% aqueous nasal spray, an established preventive treatment for seasonal allergic rhinitis, were compared in a double-blind, double-dummy, parallel-group, multicentric study in France. A total of 218 patients with seasonal allergic rhinitis caused by grass pollen (verified by positive skin prick test) were preventively treated before the onset of the grass pollen season with either fluticasone propionate 200 micrograms once daily or disodium cromoglycate 5.2 mg four times daily. Half of these doses was given in each nostril. Treatment started before the onset of the pollen season in most patients (178/218). Diary cards, including symptoms of rhinitis and usage of nasal sprays, were filled in twice daily for 6 weeks. Terfenadine in 60-mg tablets and eye-drops could be used as rescue medications. We treated 110 patients with fluticasone propionate and 108 patients with disodium cromoglycate. Patients treated with fluticasone propionate had significantly more days free of primary efficacy symptoms of sneezing (P < 0.001) and nasal discharge during the day (P = 0.002), as well as free of all the other nasal symptoms (P < 0.01), and significantly lower median scores (P < 0.05) for all nasal symptoms except nasal discharge than patients treated with disodium cromoglycate. There was no difference in eye symptoms or in rescue medication use between the two groups. Compliance with the treatment was assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Child; Cromolyn Sodium; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Middle Aged; Patient Compliance; Rhinitis, Allergic, Seasonal; Terfenadine

Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis.. To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis.. Multicenter, randomized, double-blind, placebo-controlled, parallel-group.. Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment.. Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days.. Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups.. In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

Topics: Administration, Topical; Aerosols; Androstadienes; Anti-Inflammatory Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Rhinitis, Allergic, Seasonal

In order to examine fluticasone propionate's mechanism of inhibiting nasal allergic symptoms, topical dosing of FP to patients with Japanese cedar pollinosis was started before the pollen scattering season, and the kinetics of basophilic cells and eosinophils which infiltrated into the surface of nasal mucous membrane were observed. Patients with Japanese cedar pollinosis were divided into two groups. Before and in the early period of the pollen scattering season, one group received FP and the other group a placebo, topically into the nostrils. In the mid and late season, both groups were treated with FP topical dosing. The study was carried out in the double blind manner. In the pre-, early and late season, specimens were scraped from the nasal mucosal surface, basophilic cell and eosinophil counts in the specimens were measured, and histamine and ECP contents in the specimens were also determined. Topical use of FP starting pre-season significantly inhibited symptoms of Japanese cedar pollinosis, as well as accumulation of basophilic cells and eosinophils in the nasal mucosal surface. Histamine and ECP contents in the nasal specimens tended to decrease with the topical use of FP.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Mucous Membrane; Nasal Mucosa; Pollen; Rhinitis, Allergic, Seasonal; Seasons

Fluticasone propionate was compared with beclomethasone dipropionate for the treatment of allergic rhinitis in a multicenter, double-blind, randomized, placebo-controlled study during the mountain cedar (Juniperus ashei) pollination season in central Texas. Adults (n = 313) with moderate to severe symptoms were treated with fluticasone propionate aqueous nasal spray 200 micrograms once a day or beclomethasone dipropionate aqueous nasal spray 168 micrograms twice a day or placebo for 2 weeks. Fluticasone propionate administered once daily and beclomethasone dipropionate administered twice daily were equally effective as assessed by clinician- and patient-rated scores for nasal obstruction, rhinorrhea, sneezing, and nasal itching throughout the treatment and follow-up periods. Both regimens were more effective than placebo. Adverse events were related to topical administration and were similar in frequency and nature in all three treatment groups. Fluticasone propionate and beclomethasone dipropionate displayed a similar safety profile that did not differ from placebo. We conclude that fluticasone propionate aqueous nasal spray administered as 200 micrograms once daily in the morning is as safe and effective as beclomethasone dipropionate aqueous nasal spray administered as 168 micrograms twice daily for seasonal allergic rhinitis.

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

A multicenter, double-blind, parallel-group, dose-tolerance study was conducted to evaluate the safety of fluticasone propionate aqueous nasal spray, a potent new corticosteroid preparation. Ninety-seven adult patients with moderate to severe seasonal allergic rhinitis during the fall weed season received either placebo or fluticasone propionate in doses of 50, 200, or 800 micrograms twice daily for 4 weeks. Safety evaluations included adrenal function evaluation by morning plasma cortisol concentration, response to ACTH stimulation, and 24-hour urinary free cortisol excretion. There was no evidence of effects on adrenal function at any dose. The severity, nature, and frequency of adverse events were similar across all treatment groups, including placebo. Drug-related adverse events were consistent with local nasal irritation. The groups receiving fluticasone propionate showed greater improvement in nasal symptoms (obstruction, rhinorrhea, sneezing, and itching) than did the placebo group. The results demonstrate that fluticasone propionate aqueous nasal spray is safe in doses up to 1600 micrograms per day and effective in the treatment of seasonal allergic rhinitis.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Tolerance; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal

A multicenter double-blind, randomized, parallel group study was conducted to evaluate the once daily administration of fluticasone propionate, a potent, new corticosteroid preparation, for the treatment of seasonal allergic rhinitis. Adult patients (n = 227) were treated for 2 weeks with fluticasone propionate aqueous nasal spray 200 micrograms QD or 100 micrograms BID or matching placebo during the autumn pollen season. Overall, the administration of fluticasone propionate once daily in the morning was as effective as the twice daily dosage regimen, and either regimen was more effective than placebo. Improvement in clinician-rated and patient-rated nasal symptom scores, including morning nasal obstruction, was evident within three days of fluticasone propionate therapy and continued throughout the treatment period. Fewer patients receiving fluticasone propionate used rescue medication and had nasal eosinophilia compared with patients receiving placebo. Adverse events were similar in frequency and nature in all three treatment groups. Morning plasma cortisol concentrations and response to cosyntropin stimulation were similar across groups and offered no evidence of HPA axis suppression. We conclude that fluticasone propionate aqueous nasal spray administered once daily is a safe and effective treatment for seasonal allergic rhinitis. The convenience of a once daily regimen may encourage better compliance.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Cosyntropin; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Nose; Placebos; Respiratory Function Tests; Rhinitis, Allergic, Seasonal

Fluticasone propionate is a new glucocorticosteroid with potent topical activity. In a double-blind, randomized, parallel-group study, 423 adult patients with moderate to severe seasonal allergic rhinitis received placebo or fluticasone propionate aqueous nasal spray at doses of 25, 100, or 400 micrograms twice daily (b.i.d.) for 2 weeks. Efficacy was evaluated by nasal symptom scores, nasal airflow, nasal cytology, and global evaluation. All doses of fluticasone propionate were significantly better than placebo in reducing symptoms of seasonal allergic rhinitis. Patients receiving the largest dose of fluticasone propionate (400 micrograms b.i.d.) had a slightly greater reduction (not significant) in symptom scores than patients receiving the smallest dose (25 micrograms b.i.d.). Symptom improvement was evident within 3 days of treatment. Nasal airflow improved in the groups treated with fluticasone propionate, 100 and 400 micrograms b.i.d. Examination of nasal cytograms revealed a striking decrease in both eosinophils and basophils in all three groups receiving active treatment compared with placebo. There were few adverse events and no treatment-related abnormalities in laboratory assays or evaluations of hypothalamo-pituitary-adrenocortical axis function. Comparison of treatment groups indicated that fluticasone propionate aqueous nasal spray was as safe as placebo at the doses studied.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Manometry; Multicenter Studies as Topic; Nasal Mucosa; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Rhinitis, Allergic, Seasonal

Nasal application of grass pollen allergen in atopic individuals with seasonal rhinitis leads to an early rise in nasal airways resistance. The effects of fluticasone propionate, a powerful, topically active glucocorticosteroid, on nasal airways resistance and cellular infiltration of the nasal mucous membrane were investigated. Fluticasone propionate blunted the rise in nasal airway resistance following allergen challenge (P = 0.089). Although this glucocorticosteroid did not affect the total number of eosinophils in biopsies of nasal mucous membrane, the number of activated eosinophils was significantly reduced (P less than 0.05).

Topics: Administration, Topical; Adult; Airway Resistance; Androstadienes; Anti-Inflammatory Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Male; Middle Aged; Nasal Mucosa; Pollen; Rhinitis, Allergic, Seasonal

The combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.. Moderate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self-reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples.. In nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (-2.57 to -0.45 Log2 fold change [FC]), 24 genes upregulated (0.49-1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (-1.53 to -0.58 Log2 FC), six genes upregulated (1.07-1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (-1.68 Log2 FC), four genes upregulated (0.59-1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment.. AZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression.

Topics: Fluticasone; Gene Expression; Humans; Phthalazines; Rhinitis, Allergic, Seasonal

Topics: Acetates; Adult; Anti-Allergic Agents; Cetirizine; Cryptomeria; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Mast Cells; Middle Aged; Nasal Cavity; Nasal Sprays; Neutrophils; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides; Terfenadine; Treatment Outcome

.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Fluticasone; Humans; Rhinitis, Allergic, Seasonal

Nasal rinsing with an atomizer spray was found to be effective in the treatment of allergic rhinitis. Two parameters express the nasal functions: (1) mucociliary clearance (MCC), and (2) the pH and its stability. MCC is the main factor that defines the time of pollen transition on the nasal mucosa and, therefore, the amount of the allergen glycoprotein elution.. We hypothesized that the nasal wash efficacy could be due to the reduction of contact time of the grass pollen on the nasal mucosa (improving MCC).. Forty patients with seasonal grass pollen oculorhinitis were randomized in two groups: 20 received three times daily nasal rinsing with hypertonic solution buffered to pH 6.1, before and during the peak pollen season in 2015 (active group), and another 20 patients were allocated to the control group and received no nasal treatment. The daily symptoms score and the use of oral antihistamines when required were evaluated during the grass pollen peak season. All the patients completed the study.. In comparison with the control group, in the active group, a significant decrease of both nasal symptoms (p = 0.01) and consumption of antihistamines (p = 0.035) was found. Furthermore, the MCC was significantly worse (p = 0.011) only in the control group.. The nasal treatment maintained the efficiency of the MCC in the patients in the active group, who showed a significant reduction of symptoms and medication score. The MCC decreased the transit time of the pollen on the nasal mucosa, which favored an elution of the allergenic proteins.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Male; Mucociliary Clearance; Nasal Mucosa; Nebulizers and Vaporizers; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Seasons; Therapeutic Irrigation; Young Adult

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

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

For locally acting drugs, an extended residence time in the nasal cavity is desirable and related to a prolonged effect. We sought to develop a model for comparative determination of intranasal pharmacokinetics. We embedded human respiratory tissue into a solid matrix and coated the surface with artificial nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were applied onto the surface and removed after 30 min to simulate mucociliary clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. FP and Bud were initially bound to the same extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP or Bud. After equilibrium with plasma, approximately 5-fold higher tissue concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud were determined. This tissue retention revealed an excellent correlation with the volume of distribution of the respective drugs (r=0.9999, p ≤ 0.05). The inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced compared to AZ. The present model realistically mirrors conditions in vivo where solubility and tissue absorption of intranasally applied drugs compete with mucociliary clearance mechanisms.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Administration, Intranasal; Aerosols; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Budesonide; Cell Line, Tumor; Delayed-Action Preparations; Epithelial Cells; Fluticasone; Glucocorticoids; Histamine Antagonists; Humans; Interleukin-8; Lung; Lung Neoplasms; Mucociliary Clearance; Nasal Lavage Fluid; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal

The use of systemic steroids has been established as a risk factor for the development of posterior subcapsular cataracts. In recent decades, the use of nasal topical steroids has increased in an effort to decrease systemic side effects. Current evidence of an association between nasal steroid use and cataract formation is contradictory. We present a case of rapid-onset bilateral posterior subcapsular cataracts in a young healthy patient with a history of long-term nasal steroid use.

Topics: Aberrometry; Administration, Intranasal; Adult; Androstadienes; Cataract; Fluticasone; Glucocorticoids; Humans; Male; Posterior Capsule of the Lens; Rhinitis, Allergic, Seasonal

Atrial fibrillation (AF) is the most common rhythm disorder observed in clinical practice. Several case reports and case-control studies have associated this condition with the use of systemic corticosteroids. However, to our knowledge, no case of AF induced by inhaled corticosteroids has been reported in the literature. We describe here the case of a 15-year-old boy who reported a paroxysmal AF with fast ventricular response after the administration of fluticasone propionate, which resolved after discontinuation of the drug. Use of the Naranjo adverse-drug-reaction probability scale indicated a possible relationship between the patient's development of AF and fluticasone propionate therapy. More studies are needed to confirm the association between this arrhythmia and the use of high doses of inhaled corticosteroids. Data from this report already suggest that clinicians should be aware of the possibility of adverse cardiovascular reactions when corticosteroids are prescribed also as inhaled preparations.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Atrial Fibrillation; Bronchodilator Agents; Electrocardiography; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal

Children with allergic rhinitis (AR) are reported to have disturbed sleep and daytime fatigue due to nasal obstruction.. To evaluate sleep impairment in children with AR using actigraphic evaluation.. Fourteen children aged 7 to 16 years with grass pollen-sensitized seasonal AR were enrolled. They completed the Total 4-Symptom Score (T4SS) scoring system for AR symptom score and the Pittsburgh Sleep Quality Index (PSQI) questionnaire for sleep quality, and they underwent actigraphy for 3 days in the pretreatment period. After topical corticosteroid and antihistaminic treatment for 8 weeks, actigraphy, the T4SS, and the PSQI were repeated. Fourteen healthy children aged 8 to 16 years underwent actigraphy and completed the PSQI questionnaire as controls.. There were no significant age or sex differences between the AR and control groups. Pretreatment PSQI and actigraphy scores were worse in the AR group vs the control group. After treatment, sleep quality improved, and there were no differences in actigraphy and PSQI scores between the 2 groups. Before treatment, the T4SS was significantly correlated with the sleep efficiency, daytime napping episodes, and total nap duration variables of actigraphy (r = -0.53, P = .004; r = 0.43, P = .02; and r = 0.39, P = .04, respectively). The T4SS was correlated with the total PSQI score (r = 0.67, P < .001).. Sleep can be compromised in children with AR. There is a significant correlation of clinical symptom score with the actigraphic and PSQI variables. Therefore, actigraphy may be used as an objective tool to evaluate sleep disturbance in children with AR.

Topics: Actigraphy; Adolescent; Androstadienes; Anti-Allergic Agents; Cetirizine; Child; Female; Fluticasone; Humans; Male; Rhinitis, Allergic, Seasonal; Sleep Wake Disorders

Topics: Androstadienes; Anti-Allergic Agents; Drug Therapy, Combination; Fluticasone; Humans; Phthalazines; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Eye Diseases; Fluticasone; Humans; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Conjunctivitis, Allergic; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Seasonal

The aim of this study is to determine the rate of nasal carriage of Staphylococcus aureus (NCSA) in children with allergic rhinitis (AR) and to determine the effect of intranasal fluticasone propionate spray on the NCSA.. Nasal swabs were taken from the children admitted to general pediatrics and pediatric pulmonology clinics. Patients were divided into two groups according to the presence or absence of AR. Diagnosis of AR was based on the patient's symptoms. Nasal swabs were taken from AR patients before and after the treatment with intranasal fluticasone propionate, and from the control group at the beginning and after 2 months.. Whole NCSA rate was 17.9%; it was 21.4% for AR patients and 15.9% for control group, respectively (p>0.05). Treatment with intranasal fluticasone propionate spray did not influence NCSA in AR patients.. It seemed that NCSA was not increased in children with AR and treatment with intranasal fluticasone propionate spray did not change NCSA in AR patients. It is obvious that better understanding of the factors affecting the acquisition and loss of NCSA might increase our knowledge about the relationship between NCSA, allergic airway diseases and their treatments.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Carrier State; Child; Child, Preschool; Female; Fluticasone; Humans; Male; Nose; Prevalence; Rhinitis, Allergic, Seasonal; Staphylococcal Infections; Staphylococcus aureus

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

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

Topics: Acetates; Administration, Intranasal; Administration, Oral; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Fluticasone; Humans; Leukotriene Antagonists; Loratadine; Quinolines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Sulfides

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Fluticasone; Humans; Mometasone Furoate; Patient Satisfaction; Pregnadienediols; Rhinitis, Allergic, Seasonal; Triamcinolone Acetonide

Nitric oxide (NO) in exhaled breath is produced primarily by the upper respiratory airway mucosa. The nasal output of this gas is increased in patients with allergic rhinitis. We performed a study on a 41-year-old nonsmoking male volunteer with allergic rhinitis to investigate the effect of fluticasone nasal spray on nasal NO output (VNO). A total of 28 nasal NO measurements from both nostrils were taken during the 2-month period of June and July 2002. During the second half of the study period (treatment phase), the patient took fluticasone in doses of 100 micrograms per nostril once a day. During the treatment phase, nasal NO measurements were taken 10 days after the initiation of treatment. In addition, we also recorded the patient's nasal symptom scores and the grass pollen counts in the greater Pittsburgh area. The patient's mean VNO was 989.9 nl/min prior to treatment and 787.7 nl/min following treatment--a statistically significant 20.4% decrease (p < 0.01). The findings of our study support the observation that topical nasal steroid treatment decreases NO production in sinonasal mucosa.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Breath Tests; Fluticasone; Humans; Nasal Mucosa; Nitric Oxide; Rhinitis, Allergic, Seasonal

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

Topics: Administration, Intranasal; Adult; Androstadienes; Evidence-Based Medicine; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal

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, Intranasal; Adolescent; Androstadienes; Anti-Inflammatory Agents; Back Pain; Fluticasone; Glucocorticoids; Headache; Humans; Intracranial Hypertension; Male; Rhinitis, Allergic, Seasonal

Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E-selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30-min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic rhinitis.. Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml. The expression of E-selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation.. In this model, E-selectin expression was significantly upregulated by allergen and rhIL- 1beta within 1 and 2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by > or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l, respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid upregulation of E-selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l.. Allergen-induced E-selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen-induced cytokine release.

Topics: Adolescent; Adult; Allergens; Androstadienes; E-Selectin; Fluocortolone; Fluticasone; Glucocorticoids; Humans; Interleukin-1; Middle Aged; Nasal Mucosa; Pollen; Prednisolone; Recombinant Proteins; Rhinitis, Allergic, Seasonal; Up-Regulation

Topics: Administration, Intranasal; Androstadienes; Fluticasone; Humans; Rhinitis, Allergic, Seasonal

Nitric oxide (NO) is produced by the action of NO synthase (NOS) using L-arginine as a substrate in various cells and found in air exhaled by humans. Previous studies suggest that almost all exhaled NO is derived from the upper airways and increases in patients with untreated asthma and allergic rhinitis. Exhaled NO is inhibited by treatment with inhalation of steroids that may be caused by inhibition of inducible nitric oxide synthase (iNOS). The purpose of this study is to determine whether exhaled and nasal NO increases in patients with Japanese cedar pollinosis compared with nonallergic healthy subjects, and whether it is affected by treatment with nasal steroids. Furthermore, we investigated its relation to nasal function and allergic rhinitis.. 10 patients with Japanese cedar pollinosis and 5 healthy normal subjects were tested. All subjects had no history of respiratory infection for at least 2 weeks and did not smoke. Exhaled NO was collected in a sampling bag from oral and nasal breathing, and nasal NO was sampled directly from the nasal cavity. Both were measured by a chemiluminescence NO analyzer, ML9841, at a detection limit of 1 part per billion (ppb). Subjects used nasal steroids for 2 weeks and were measured similarly afterwards.. NO concentrations in nasal air and air exhaled from the nose in patients with Japanese cedar pollinosis (277.9 +/- 59.5 ppb, 34.4 +/- 3.9 ppb, n = 10) were higher than the normal subjects (153.3 +/- 30.6 ppb, 19.9 +/- 3.4 ppb, n = 5) (p < 0.05). NO exhaled from the mouth was not significantly different between patients (20.5 +/- 4.9 ppb) and normal subjects (23.7 +/- 2.6 ppb). In patients with Japanese cedar pollinosis, the concentration of nasal NO and nasal exhaled NO were significantly decreased after treatment with nasal steroids (144.0 +/- 21.0 ppb, 26.1 +/- 3.0 ppb) (p < 0.01, p < 0.05), but there was no change in oral exhaled NO (17.2 +/- 3.3 ppb). In normal subjects, oral (22.5 +/- 5.3 ppb), nasal exhaled NO (19.1 +/- 2.3 ppb), and nasal NO (151.2 +/- 24.8 ppb) were not changed.. In patients with Japanese cedar pollinosis, nasal NO was increased and decreased by nasal steroids. These results suggest that increased nasal NO in patients with allergic rhinitis is produced by induction of iNOS and that nasal NO produces the symptoms of nasal obstruction and rhinorrhea.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Breath Tests; Female; Fluticasone; Humans; Male; Nasal Cavity; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Pollen; Rhinitis, Allergic, Seasonal; Trees

Topics: Androstadienes; Anti-Allergic Agents; Fluticasone; Humans; Pollen; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Terfenadine

Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability.. Using this glucocorticoid inhibition of eosinophil viability, we compared the in vitro potencies of several inhaled glucocorticoids with particular attention to fluticasone 17-propionate.. Eosinophils from normal or mildly atopic donors were purified, cultured with cytokines and glucocorticoids, and on day 4, after staining with propidium iodide, analysed by flow cytometry.. Eosinophil viability was prolonged by interleukin (IL)-5 in a concentration-dependent manner; in contrast, dexamethasone inhibited the IL-5 effect. Fluticasone 17-propionate, 1.0-1000 nM, also inhibited the IL-5 effect in a concentration-dependent manner; interestingly, at 0.1 nM fluticasone 17-propionate modestly, but significantly, enhanced eosinophil survival. High concentrations of IL-5 and granulocyte-macrophage colony-stimulating factor essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17-propionate on eosinophil survival. In contrast, although interferon-gamma-mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17-propionate, this inhibition was not overcome by increased concentrations of interferon-gamma. Comparison of the glucocorticoid inhibition of eosinophil viability in the presence of 10 pg/mL IL-5 resulted in these drug IC50 values (in nM): fluticasone 17-propionate, 1.3; budesonide, 8.5; triamcinolone acetonide, 25; flunisolide, 32; dexamethasone, 94; beclomethasone 17-monopropionate, 210; beclomethasone 17,21-dipropionate, 290; and hydrocortisone, >1000.. Fluticasone 17-propionate's effect on cytokine-mediated eosinophil viability is similar qualitatively to other glucocorticoid preparations. However, quantitatively, fluticasone 17-propionate has the most potent suppressive effects on IL-5 mediated eosinophil viability among the currently available inhaled glucocorticoids in the United States.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Cell Separation; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Eosinophils; Flow Cytometry; Fluticasone; Humans; Interleukin-5; Rhinitis, Allergic, Seasonal

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; Androstadienes; Anti-Allergic Agents; Drug Combinations; Fluticasone; Humans; Loratadine; Research Design; Rhinitis, Allergic, Seasonal

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Fluticasone; Glucocorticoids; Humans; Rhinitis, Allergic, Seasonal; Terfenadine

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

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Drug Approval; Fluticasone; Glucocorticoids; Humans; Rhinitis, Allergic, Seasonal; United States