The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.     

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis

INTRODUCTION: 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. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENTS AND RESULTS: 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. CONCLUSION: 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.     

Mometasone furoate. A review of its intranasal use in allergic rhinitis

Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. CONCLUSIONS: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.     

Nedocromil sodium is rapidly effective in the therapy of seasonal allergic rhinitis

BACKGROUND: Nedocromil sodium has proven to be efficacious in prophylactic and long-term therapy for the treatment of seasonal allergic rhinitis. We examined the speed of onset of intranasal nedocromil sodium (1%) for relief of symptoms due to ragweed allergic rhinitis. METHODS: In a double-blind, placebo-controlled trial, 104 patients received either nedocromil sodium or placebo four times daily. Patients spent 10 hours per day for 2 consecutive days in Iowa City Park during the peak of ragweed season. Only patients who had significant symptoms during 3 hourly baseline assessments received drug. Symptom scores for stuffy nose, runny nose, itchy nose, and sneezing and global symptom summary scores were recorded at 19 hourly time points during the 2 days. In the evening patients recorded symptom scores for the postexposure period. RESULTS: In comparison with placebo, nedocromil significantly improved rhinitis symptoms as evidenced by lower symptom summary scores within 2 hours (p = 0.016). Further, this reduction in rhinitis symptoms was maintained throughout the 2-day pollen exposure period. After patients left the study site, postexposure symptom summary scores were also significantly lower in patients treated with nedocromil compared with those treated with placebo (p < 0.007). CONCLUSIONS: Nedocromil significantly relieved preexisting seasonal allergic rhinitis symptoms during peak pollen exposures within 2 hours of the first dose, and the therapeutic benefits were maintained on a dosing regimen of four times a day.     

Cervical actinomycosis. A rare differential diagnosis of parotid tumor]

BACKGROUND: Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. OBJECTIVE: To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. METHODS: A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. RESULTS: Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. CONCLUSION: A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine nasal spray.     

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NME1 (Nm23)

BACKGROUND: Nasal immunotherapy with single allergen extracts, following premedication with cromolyn, has been reported to be effective in treating seasonal and perennial allergic rhinitis. METHODS: We conducted a double-blind, placebo-controlled study to assess the efficacy, tolerability, and mechanism of action of nasal immunotherapy for allergic rhinitis caused by weed pollens from three unrelated families. Twenty-seven weed-allergic patients underwent baseline nasal provocation and titrated skin test with a mixed weed extract containing ragweed, sage, and Chenopod extracts. Patients were randomized to receive either mixed weed extract or placebo. Nasal immunotherapy was self-administered daily to alternate nostrils preceded by 5.2 mg intranasal cromolyn. Beginning with 1:2500 wt/vol the concentration was increased to 1:10 wt/vol over an average period of 36 days. The maintenance dose (1:10 wt/vol) was administered daily for 12 to 16 weeks through the weed pollen season. Patients recorded nasal and eye symptoms and the use of rescue medications throughout the study. A nasal lavage for cytokine levels and nasal scraping with Rhinoprobe for nasal cytology were performed at the peak of the weed season. Nasal provocation and titrated skin tests with mixed weed extract were repeated after the weed season. Nasal lavage and scraping were also performed before and 24 hours after the final nasal provocation. RESULTS: During the peak weeks of the weed season the group receiving mixed weed extract by nasal instillation, compared with those treated with placebo, had significantly lower total nasal symptom scores, total eye symptom scores, and symptom medication scores. There were no significant differences in the nasal cytology or cytokines levels between the two groups, except for elevated IL-10 in the nasal lavage in the treated group at the peak of the season. Nasal symptoms and medication use were higher preseasonally in the active treatment group. CONCLUSION: Nasal immunotherapy with aqueous mixed weed extract administered with cromolyn sodium pretreatment for 17 to 21 weeks was effective in reducing both nasal and ocular symptoms of weed pollen-induced allergic rhinitis. There were increased nasal symptoms in the treated group preseasonally.     

Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa

BACKGROUND: Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated. OBJECTIVE: To study the effect of fluticasone propionate aqueous nasal spray compared to placebo nasal spray in the treatment of rhinitis medicamentosa. METHODS: A parallel randomized, double-blind study was conducted to evaluate the treatment of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray immediately and were treated with either fluticasone propionate nasal spray once daily 200 micrograms, or placebo nasal spray for 14 days. The nasal mucosal swelling was recorded with rhinostereometry, acoustic rhinometry and a peak inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale in the morning and in the evening of each day. RESULTS: The mucosal swelling decreased after 7 and 14 days of treatment with fluticasone propionate as well as placebo, but the reduction was significantly greater after treatment with fluticasone propionate. The symptom scores for nasal stuffiness showed a marked reduction during the treatment period in both groups, but there was a faster onset of symptom reduction after treatment with fluticasone propionate. CONCLUSION: Fluticasone propionate is more effective and has a faster onset of action than placebo in the treatment of rhinitis medicamentosa. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process.     

Intranasal azelastine. A review of its efficacy in the management of allergic rhinitis

Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes, after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement. Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine. Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR). Conclusion: Twice-daily intranasal azelastine offers an effective and well tolerated alternative to other antihistamine agents currently recommended for the symptomatic relief of mild to severe SAR and PAR in adults and children (aged > or = 12 years in the US; aged > or = 6 years in some European countries including the UK). The rapid onset, confined topical activity and reduced sedation demonstrated by the intranasal formulation of azelastine may offer an advantage over other antihistamine agents, although this has yet to be confirmed.     

Onset of action of aqueous beclomethasone dipropionate nasal spray in seasonal allergic rhinitis

Beclomethasone dipropionate nasal spray is widely used in the treatment of seasonal allergic rhinitis; however, the time of onset of action has not been determined. This study assessed the onset of action, level of relief, and efficacy of beclomethasone nasal spray in patients with seasonal allergic rhinitis. In a double-blind, randomized, placebo-controlled, parallel-group, multicenter, 7-day study, symptomatic patients were administered two inhalations of beclomethasone dipropionate (n = 80) or placebo (n = 81) into each nostril twice daily. Patients assessed the onset of action and level of relief at 6, 24, and 48 hours and at days 3 and 7. Investigators evaluated symptoms at days 0, 3, and 7 and response to therapy at days 3 and 7. The difference in the cumulative number of patients reporting relief of symptoms was statistically significant in favor of beclomethasone dipropionate by hour 24 (P = 0.05). Patients in the beclomethasone dipropionate group experienced a greater level of relief than patients receiving placebo at hour 24, and improvement increased over the 7-day study compared with a decrease in relief in the placebo group. Beclomethasone dipropionate was significantly more effective than placebo in reducing symptoms (P < or = 0.02), and patients in the beclomethasone dipropionate group showed a more favorable response to treatment than did patients in the placebo group (P < 0.01). Adverse events were minor in both groups. Beclomethasone dipropionate nasal spray produced significant onset of relief of symptoms the first day of treatment; improvement was sustained and increased over the course of the study.     

The role of partial splenectomy in children with thalassemia

AIM OF THE STUDY: To study the changes in nasal reactivity in patients with rhinitis medicamentosa during treatment with placebo or fluticasone propionate, in order to better understand the mechanisms of nasal congestion in such patients. STUDY DESIGN: A parallel, double-blind study. Twenty patients with rhinitis medicamentosa were randomized to either placebo or fluticasone treatment during 14 days. MATERIAL AND METHODS: Nasal mucosa reactivity was studied with a histamine challenge model using three concentrations of histamine to challenge the nasal mucosa (1, 2 and 4 mg histamine/ml). Recordings of the nasal mucosa response were made 5 min after each challenge, using rhinostereometry and acoustic rhinometry, before and after the period of treatment. RESULTS: The fluticasone group had a significantly increased histamine sensitivity after treatment, unlike the placebo group who had an unchanged or slightly decreased histamine sensitivity after treatment. CONCLUSIONS: The results of this study support the theory that the nasal obstruction in rhinitis medicamentosa is due to interstitial oedema rather than to vasodilatation. On the first day of vasoconstrictor withdrawal, the inferior concha was congested and oedematous with a limited capacity to respond to histamine challenge. However, after 14 days of treatment with a corticosteroid nasal spray, the oedema was reduced and the increase in histamine sensitivity reflected the persistence of nasal hyperrreactivity. In the placebo group, histamine sensitivity remains unchanged with the measuring technique we used. This probably indicates that oedema was still present after treatment.     

Effect of betotastine besilate (TAU-284), a novel anti-allergic agent, on experimental allergic rhinitis

We investigated the effect of betotastine besilate (betotastine) on the experimental allergic rhinitis. The oral administration of betotastine (1, 3 and 10 mg/kg) inhibited the increase in dye leakage during and after the nasal perfusion of antigen in actively sensitized rats. It also prevented the increase in intranasal pressure induced by topically applied histamine in non-sensitized guinea pigs. Cetirizine and terfenadine dose-dependently inhibited the increase in a similar manner. Ketotifen (0.01-0.3 mg/kg, p.o.) inhibited the increase more than 50% at 0.01 mg/kg. The ID50s of ketotifen, cetirizine, betotastine and terfenadine for this model were more than 0.01 mg/kg, 0.01 mg/kg, 0.03 mg/kg and 0.5 mg/kg, respectively. Furthermore, in actively sensitized guinea pigs, nasal airway resistance showed a biphasic increase after the topical antigen challenge to the nasal cavity; the first peak at 0.5 hr and a second peak at 4 hr. Both the responses of first and second peaks were significantly inhibited by orally administered betotastine besilate, and its inhibitory effect on the second peak was the strongest among drugs tested. Since betotastine showed significantly inhibitory effects in experimental allergic rhinitis models, it was suggested to show a good efficacy for the treatment of allergic rhinitis clinically.     

Hong Kong''s eastern and western medical history

BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.     

Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: a pilot study

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.     

Preseasonal intranasal immunotherapy in birch-alder allergic rhinitis. A double-blind study

A double-blind, placebo-controlled study was carried out to test the clinical efficacy and safety of local nasal immunotherapy (LNIT) in powder form. Twenty-two patients suffering from allergic rhinitis strictly associated with early spring symptoms, with positive skin prick tests and RAST for birch-alder, all responders to a specific nasal provocation test (NPT), received randomly active or placebo treatment for 4 months. Immunotherapy consisted of administration of a set of capsules containing progressively increasing amounts of birch (Betula pendula) and speckled alder (Alnus incana) allergens in powder form with controlled granulometry. The active (birch-alder) and placebo (lactose) group completed the treatment according to a similar schedule. During the pollen season (March-April), the patients who took the active treatment reported less sneezing and rhinorrhea than the placebo group, on the basis of a symptoms score, and the differences were statistically significant; the need for drugs (terfenadine) was also significantly reduced. These findings agreed well with the results of specific NPT after the treatment; only patients in the active group had a higher threshold dose of nasal specific reactivity to birch-alder allergens than in tests before the LNIT.     

Circulating dopamine-beta-hydroxylase (DbetaH) and catecholamines in a paediatric phaeochromocytoma

Nasal airways resistance was measured in ten patients with allergic rhinitis during intranasal application of an extract of grass pollen. Pretreatment with placebo did not inhibit the increase in nasal airways resistance, whereas ICI 74,917 administered from a pressurized aerosol gave almost complete protection. ICI 74,917 was well tolerated and no evidence was obtained of local hyposensitization during the period of the study.     

The effect of terfenadine on unilateral nasal challenge with allergen

To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.     

Pharmacotherapy in the elderly--pharmacokinetic and pharmacodynamic considerations]

OBJECTIVE: N-acetyl-aspartyl-glutamic acid (NAAGA) was effective in the treatment of allergic rhinitis, with an action on early allergen-induced nasal symptoms and mediator release. The aim of this study was to evaluate the clinical activity of NAAGA and its effects on the late antigen-induced reaction in the nose. METHODS: Ten patients with allergic seasonal rhinitis were included in this randomized double-blind crossover trial of a 6% wt/vol solution of NAAGA (daily dosage 84 mg) versus placebo (lactose). The drug and placebo were administered intranasally five times daily for 1 week, with a 2-week interval between treatments. RESULTS: Treatment with NAAGA, but not with placebo, significantly reduced the late antigen-induced nasal symptoms, mainly nasal obstruction. Eosinophil numbers in the nasal lavages collected 6 h and 24 h after challenge were significantly lower after NAAGA than after placebo. Active treatment also significantly reduced the neutrophil count 6 h after antigen challenge, and significantly lowered eosinophil cationic protein and myeloperoxidase levels in nasal lavages 6 h and 24 h after antigen challenge. CONCLUSION: These results indicate that treatment for 1 week with NAAGA can reduce the late antigen-induced reaction in the nose. This is accompanied by a reduction in eosinophil and neutrophil recruitment and release of eosinophil cationic protein and myeloperoxidase.     

Expression of IL-16 in allergen-induced late-phase nasal responses and relation to topical glucocorticosteroid treatment

Allergen-induced late nasal responses (LNRs) are associated with a cellular infiltrate in which CD4+ cells are prominent. These cells have been shown to be the major cellular source of Th2-type cytokines. Mechanisms responsible for the local accumulation of CD4+ cells in the nasal mucosa after allergen exposure are unclear. IL-16 is a potent chemoattractant for CD4+ cells in vitro and may play a significant role in recruiting CD4+ cells in LNRs. We investigated the expression of IL-16 messenger RNA and immunoreactivity in nasal biopsy specimens from 17 subjects with allergic rhinitis. A biopsy specimen of the nasal inferior turbinate was obtained before and 24 hours after local nasal provocation with grass pollen extract after 6 weeks of treatment with either topical fluticasone propionate (n = 9) or placebo (n = 8) nasal spray twice daily. IL-16 mRNA-positive cells and IL-16-immunoreactive cells were identified in both the epithelium and the subepithelial tissue at baseline. Within the placebo-treated group, the numbers of epithelial and subepithelial IL-16 mRNA-positive cells and IL-16-immunoreactive cells were significantly increased 24 hours after challenge compared with baseline (p < 0.001). Topical glucocorticoid therapy resulted in a decrease in allergen-induced epithelial immunoreactive cells and subepithelial IL-16 mRNA-positive cells. The numbers of CD4+ cells increased after antigen challenge compared with baseline (p < 0.05), and this increase was inhibited by glucocorticoid treatment. There were significant correlations between epithelial and subepithelial IL-16 immunoreactivity and CD4+ cell infiltration after antigen challenge. The upregulation of IL-16 expression in allergic nasal mucosa after antigen challenge may have critical implications in the accumulation of CD4+ cells in response to antigen exposure. Steroid-mediated inhibition of IL-16 may be partly responsible for the decrease in local CD4+ cells after topical glucocorticoid therapy.