A clinical trial of a microcrystalline cellulose topical nasal spray on the acute response to allergen challenge.

BACKGROUND: Allergic rhinitis is a common disorder that leads to a negative impact on quality of life. Multiple options are available for treatment of the symptoms, but preventing the reaction should be an effective strategy. OBJECTIVE: We tested a nasal spray that contained microcrystalline cellulose designed to limit airborne allergens from penetrating the nasal mucosa (nasal blocker) and, therefore, prevent the initiation of the allergic reaction. METHODS: We performed a randomized, double-blind, placebo-controlled, two-way crossover clinical trial with 20 subjects who had a history of seasonal grass and/or ragweed allergy symptoms. Each subject underwent two separate nasal challenges with antigen (provocations) after application of the investigational product or placebo to both nostrils. The allergen was delivered into one nostril at a time and was administered at 2-hour intervals (identified as challenge 1 and challenge 2). We assessed peak nasal inspiratory flow and total nasal symptoms as well as the number of sneezes recorded at both 15-minute and 1-hour intervals after challenge 1 and, later, challenge 2. After a washout period, the subjects returned to undergo the alternate therapy. RESULTS: There was a significant overall decrease in peak nasal inspiratory flow after both treatments (investigational product, p = 0.005; placebo, p = 0.001), but, when the average of the change from baseline in peak nasal inspiratory flow was compared with the baseline, the results showed no significant differences between the groups (p = 0.31). Similar results were obtained for total nasal symptoms. CONCLUSION: The investigational product did not prove to be significantly better than placebo in treating seasonal allergic rhinitis symptoms.

A pilot study of the effects of intranasal budesonide delivered by NasoNeb® on patients with perennial allergic rhinitis.

BACKGROUND: We investigated whether nebulization of budesonide via a NasoNeb® device would treat perennial allergic rhinitis. METHODS: We performed a parallel, randomized, double-blind, placebo-controlled, pilot study in subjects (n = 40) with perennial allergic rhinitis. After recording baseline symptoms, subjects were randomized to budesonide respules (0.25 mg) or an equivalent placebo for 26 days. Nasal peak inspiratory flow (NPIF) and nasal symptoms (graded on a 0­3 scale) were recorded by the subjects twice daily. Rhinoconjunctivitis quality of life (RQOL) as well as nasal volume, measured by acoustic rhinometry, was obtained at baseline, after 2 weeks, and at the end of treatment. RESULTS: The average change from baseline in symptoms over the treatment period was greater for the group on budesonide (−3.33) compared to placebo (−1.98) (p = 0.45). When the average change from baseline over the treatment period was compared between the groups, budesonide resulted in higher NPIF (36.4 L/min) than placebo (18.7 L/min), p = 0.094. QOL improved in both groups compared to baseline with no significant difference between the groups. Although acoustic rhinometry indicated a larger volume in the group treated with budesonide on the last trial visit, the differences between the groups were not significant when accounting for the baseline values. CONCLUSION: Compared to placebo, administration of nebulized budesonide in subjects with perennial allergic rhinitis resulted in improvements in symptoms and objective measures of nasal congestion which approached but did not achieve statistical significance. A higher dose of active agent, a less effective placebo and a larger number of subjects might have improved statistical significance.

Evidence of maxillary sinus inflammation in seasonal allergic rhinitis.

OBJECTIVE: Allergic rhinitis has been frequently associated with both acute and chronic sinusitis. Previous studies have shown an influx of eosinophils into the maxillary sinus after nasal challenge with allergen. The objective of this study was to determine, in humans, if the development of seasonal allergic inflammation, secondary to natural allergen exposure, leads to similar inflammation within the maxillary sinus. STUDY DESIGN: Prospective, longitudinal study. Setting. Academic medical center and research laboratory. SUBJECTS AND METHODS: Eighteen subjects were evaluated in and out of the ragweed allergy season using subjective measures (nasal symptoms, quality of life), nasal secretory response to methacholine challenge, and evaluation of biomarkers in nasal and sinus lavages. RESULTS: The subjects became symptomatic during the season and reported worse quality of life and increased nasal reactivity to methacholine. The total number of eosinophils obtained by nasal lavage during the season (median= 35,691) was significantly higher compared with out of season (median = 2811, P ≤ .02). Similarly, there were significantly more eosinophils, albeit to a lesser magnitude, in the maxillary sinus during the season (median = 4248) compared with the out-of-season samples (median = 370, P ≤ .02). CONCLUSION: The authors provide evidence that natural exposure to pollen during an individual's allergy season leads to both nasal and sinus inflammation, strengthening the association between allergic rhinitis and sinusitis. The mechanism of this inflammatory response needs to be elucidated.

The effect of intranasal carbon dioxide on the acute response to nasal challenge with allergen.

Intranasal carbon dioxide (CO(2)) was shown to reduce symptoms of seasonal allergic rhinitis (SAR). This study was designed to evaluate the effect of CO(2) on nasal allergen challenge. We conducted a randomized, controlled, crossover trial in 12 subjects with SAR outside their pollen season. Thirty minutes after a 20-second exposure to CO(2) or no exposure, subjects underwent a unilateral, localized, nasal allergen challenge. Filter paper disks were placed on the nasal septum to deliver a sham challenge followed by 2 increasing doses of either grass or ragweed allergen. Secretions were collected from both sides of the septum to evaluate the nasonasal reflex and were assayed for histamine. Nasal and eye symptoms were recorded. The primary outcome measure was the contralateral, reflex, secretory response to allergen as measured by secretion weights. Secondary outcome measures included ipsilateral nasal secretion weights, nasal and eye symptoms, levels of histamine in nasal secretions, and eosinophils in nasal scrapings. Subjects reported a transient burning sensation during exposure to CO(2). Compared with no treatment, active treatment resulted in a significant reduction in sneezes (p = 0.05), contralateral secretion weights (p = 0.04), and bilateral runny nose symptoms (p = 0.01). Ipsilateral secretion weights were numerically reduced. Histamine levels in ipsilateral nasal secretions increased significantly when the subjects received sham treatment but did not increase after pretreatment with CO(2). Treatment with nasal CO(2) resulted in partial reduction of the acute response to allergen challenge. Reflex responses were reduced, supporting an effect on neuronal mechanisms, which predict usefulness in the treatment of allergic rhinitis. Registered with the U.S. National Institutes of Health clinicaltrials.gov. Identifier: NCT00618410.

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis.

BACKGROUND: In clinical trials, only about 60% of subjects report an excellent response to intranasal steroids, suggesting a need to add therapies to intranasal steroids to provide additional efficacy. OBJECTIVE: To determine whether the combination of fluticasone furoate and oxymetazoline is more efficacious than either agent alone, and to determine whether rhinitis medicamentosa develops after treatment. METHODS: We performed a double-blind, double-dummy, randomized, placebo-controlled parallel study. Sixty patients with perennial allergy were randomized to 4 weeks of once-a-night treatment with fluticasone furoate, oxymetazoline hydrochloride, the combination, or placebo. They were monitored during treatment and for 2 weeks posttreatment. RESULTS: The total nasal symptom score over the 4 weeks of treatment was lower with the combination (median, 143; range, 30-316) compared with treatment with placebo (262; 116-358) and oxymetazoline alone (219; 78-385; ANOVA, P = .04). When acoustic rhinometry was compared between the groups at the end of 4 weeks of treatment, the combination resulted in significantly higher nasal volume (mean + SEM, 15.8 + 1.1 mL; P< .03) compared with both placebo (12.1 + 0.9 mL) and oxymetazoline (12.4 + 0.8 mL) alone. The quality of life data showed no significant differences among the groups. Peak flow showed a nonsignificant improvement with the groups on fluticasone furoate. There was no evidence of rhinitis medicamentosa. CONCLUSION: The addition of oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. The lack of development of rhinitis medicamentosa suggests the need for a large multicenter study to develop a once-a-day combination of an intranasal steroid and a long-acting topical decongestant.

Effect of the addition of montelukast to fluticasone propionate for the treatment of perennial allergic rhinitis.

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

Fluticasone furoate nasal spray reduces the nasal-ocular reflex: a mechanism for the efficacy of topical steroids in controlling allergic eye symptoms.

BACKGROUND: Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms associated with allergic nasal symptoms, even though they do not reach the eye. OBJECTIVE: To elucidate a mechanism to explain these observations. METHODS: We performed a double-blind, placebo-controlled, crossover experiment in 20 subjects with seasonal allergic rhinitis. Nasal antigen challenge was performed consecutively for 3 days after 1 week of treatment with either placebo or fluticasone furoate nasal spray (FFNS). Subjects recorded their nasal and ocular symptoms, and nasal secretions were quantified. Nasal scrapings to quantify eosinophils were obtained before each antigen challenge. RESULTS: Nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex. Priming in the number of sneezes, contralateral nasal secretion weights, and total eye symptoms were observed. Treatment with FFNS reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions. CONCLUSIONS: We confirmed that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. FFNS reduced eosinophil infiltration, priming, and ocular symptoms. Furthermore, our results support a mechanism by which control of eye symptoms can be achieved during nasal administration of an intranasal steroid in patients with seasonal allergic rhinitis.

Effect of changing airway pressure on the ability of the human nose to warm and humidify air.

OBJECTIVES: Nasal continuous positive airway pressure (CPAP) treatment causes nasal symptoms that are believed to result from the drying effects of the air on the nasal mucosa, and these symptoms affect compliance with therapy. We hypothesized that the increased air pressure on the nasal mucosa caused by positive pressure from CPAP would decrease the ability of the nose to warm and humidify inspired air, explaining these symptoms. METHODS: We performed a 4-way crossover trial using CPAP pressures of -5, 0, +5, and +10 cm H2O in 10 subjects. The ability to warm and humidify inspired air was determined by measurement of the temperature of a fixed volume of cold, dry air entering and exiting the nostril and calculation of the amount of water supplied to the airstream by the nose. RESULTS: The water content of air was unaffected at the pressures studied. CONCLUSIONS: The pressure of delivered CPAP does not affect the ability of the nose to warm and humidify inspired air.

Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis.

BACKGROUND: Allergic patients often complain of eye symptoms during the allergy season. A possible mechanism for these eye symptoms is a nasal ocular reflex. OBJECTIVE: To demonstrate eye symptoms after nasal allergen challenge. METHODS: In a double-blind, placebo-controlled, crossover, clinical trial, 20 patients with seasonal allergic rhinitis were challenged in 1 nostril with antigen, and the response was monitored in both nostrils and in both eyes. Symptoms were recorded. Filter paper disks (intranasally) and Schirmer strips (intraocularly) were used for collecting secretions, which were subsequently eluted for the measurement of histamine and albumin levels. Patients were treated once topically at the site of challenge with azelastine or placebo. RESULTS: After placebo treatment, ipsilateral nasal challenge caused nasal symptoms and an increase in secretion weights; both were blocked by treatment with azelastine. Histamine and albumin levels increased only at the site of nasal challenge. Azelastine pretreatment inhibited the increase in albumin but not histamine levels. Symptoms of itchy and watery eyes increased significantly compared with symptoms with sham challenge after nasal allergen and were blocked by azelastine use. Ocular secretion weights increased bilaterally after placebo use and were not inhibited by azelastine use. CONCLUSIONS: Nasal allergen challenge releases histamine at the site of the challenge, which probably initiates a nasonasal and a nasal ocular reflex. This reflex is reduced by an H1-receptor antagonist applied at the site of the challenge. The eye symptoms associated with allergic rhinitis probably arise, in part, from a naso-ocular reflex.

Nasal challenge with allergen leads to maxillary sinus inflammation.

BACKGROUND: Allergic rhinitis and chronic rhinosinusitis are both characterized by chronic inflammation. OBJECTIVE: We sought to investigate the effect of nasal allergen challenge on the maxillary sinus and study the effect of premedication with loratadine. METHODS: We performed a double blind, crossover, randomized, placebo-controlled study in 20 allergic subjects out of season. After treatment with either placebo or loratadine (10 mg PO daily) for 1 week, a catheter was inserted into one maxillary sinus and used to lavage the cavity. The subjects then underwent nasal challenge with diluent for the allergen extract, followed by 3 concentrations of grass or ragweed. Nasal and ipsilateral sinus lavages were performed after each challenge and then hourly for 8 hours. Sneezes and symptoms were recorded, and the lavage specimens were evaluated for eosinophils and levels of eosinophil cationic protein, albumin, and histamine. Eleven of the subjects underwent a similar challenge with lactated Ringer's solution. RESULTS: Compared with the lactated Ringer's solution challenge, allergen challenge resulted in significant increases in most early- and late-phase nasal parameters. Allergen challenge of the nose also led to a significant increase compared with control values in maxillary sinus eosinophils and the levels of albumin, eosinophil cationic protein, and histamine during the late response. Loratadine resulted in significant inhibition of the nasal early response compared with that seen with placebo (P < .05). CONCLUSION: These findings suggest that a neural reflex or systemic allergic inflammation is responsible for the sinus inflammatory response and that this inflammatory response might play a role in the development of rhinosinusitis in allergic subjects.

Elucidating the mechanism underlying the ocular symptoms associated with allergic rhinitis.

Ocular symptoms occur in approximately 40% of patients with allergic rhinitis. The purpose of this study was to determine whether nasal challenge with antigen induces a nasal-ocular reflex. We performed a double-blind crossover trial in 20 subjects. A nasal challenge with antigen was performed in one nostril, and the response was assessed in both nostrils and both eyes. Subjects were treated before challenge with either placebo or azelastine, an H(1)-antihistamine. Nasal challenge with antigen led to a nasonasal reflex and a nasal-ocular reflex as manifested by an increase in symptoms and secretion weights. Treatment with azelastine reduced both reflexes. A nasal-ocular reflex follows nasal challenge with antigen and probably contributes to the ocular symptoms associated with allergic rhinitis.

Comparison of montelukast and pseudoephedrine in the treatment of allergic rhinitis.

OBJECTIVE: To compare montelukast sodium and pseudoephedrine hydrochloride in the treatment of seasonal allergic rhinitis. DESIGN: A 2-week, parallel, randomized, double-blind study with rolling enrollment. SETTING: Tertiary care medical center. PATIENTS: A total of 58 adult subjects with ragweed allergic rhinitis as documented by positive findings on a skin test to ragweed and history of symptoms during previous seasons. INTERVENTIONS: After recording their own baseline nasal symptoms, nasal peak inspiratory flow (NPIF), and diurnal and nocturnal rhinoconjunctivitis quality of life (QOL) scores, subjects were randomized to receive daily morning oral doses of either pseudoephedrine hydrochloride (240 mg) or montelukast sodium (10 mg) for 2 weeks. They recorded their nasal symptoms and NPIF twice daily during this time, and at the end of the study, they completed another QOL questionnaire and 2 tolerability profiles. MAIN OUTCOME MEASURES: Nasal symptoms, NPIF, QOL scores, and tolerability profiles. RESULTS: Both active treatments resulted in significant improvements from baseline in all symptoms of allergic rhinitis as well as in all the domains of the QOL questionnaires. When changes from baseline were compared between treatments, there were no significant differences except in the symptom of nasal congestion, for which pseudoephedrine was more effective than montelukast. Both treatments resulted in a significant increase in NPIF over baseline with no significant difference between treatments. Both drugs were well tolerated with no differences in the tolerability profiles between treatments. CONCLUSIONS: Pseudoephedrine and montelukast are equivalent in improving symptoms and QOL and increasing nasal airflow in patients with seasonal allergic rhinitis. The lack of the usual adverse effects in the pseudoephedrine group is ascribed to morning dosing.

Total IgE levels do not change 1 year after endoscopic sinus surgery in patients with chronic rhinosinusitis.

BACKGROUND: Total IgE levels positively correlate with the amount of mucosal thickening on sinus CT scans. Our objective was to investigate whether the levels of total serum IgE decreased 1 year after endoscopic sinus surgery in patients with chronic rhinosinusitis, suggesting that the total IgE was influenced by the sinus disease. METHODS: 55 patients about to undergo endoscopic sinus surgery for chronic rhinosinusitis were enrolled in a prospective clinical study. All patients had preoperative sinus computerized tomography (CT) scans and levels of total serum IgE measured before surgery and 1 year postoperatively. RESULTS: Preoperative total IgE levels showed a significant correlation with the extent of disease on sinus CT (r(s) = 0.413, p = 0.002). Total serum IgE levels did not show any statistically significant change from the preoperative values when measured 1 year postoperatively (324.25 +/- 217.30 ng/ml vs. 326.35 +/- 204.50 ng/ml; p = 0.61). CONCLUSIONS: The levels of total serum IgE do not change after sinus surgery for chronic rhinosinusitis. IgE levels in chronic rhinosinusitis may reflect a systemic factor in disease pathogenesis, and are probably not related to the amount of local inflammation within the sinuses.

Increased nasal airflow with budesonide compared with desloratadine during the allergy season.

OBJECTIVE: To compare the effects of desloratadine, an H1-blocking antihistamine, and budesonide, an intranasal corticosteroid, on nasal peak inspiratory flow (NPIF) in patients with seasonal allergic rhinitis. DESIGN: We performed a randomized, double-blind, double-dummy, parallel study comparing oral desloratadine, 5 mg/d (n = 31), and budesonide, 32 mug/d per nostril (n = 30), for 2 weeks during the spring allergy season. MAIN OUTCOME MEASURES: Subjects recorded NPIF and nasal symptoms twice daily. Baseline measurements were obtained before initiation of treatment. The Rhinoconjunctivitis Quality of Life Questionnaire was completed at baseline and after treatment. RESULTS: Desloratadine and budesonide caused a significant increase in NPIF compared with baseline on the evening of the first dose (P < .01). Budesonide, however, led to a significantly greater increase in NPIF than did desloratadine when the change from baseline was compared for the entire treatment period (median, 475 vs 150 L/min; P = .01). Both treatments resulted in clinically significant reductions of the individual domains and overall scores on the Rhinoconjunctivitis Quality of Life Questionnaire (P < .01). There was a significant reduction in total symptom scores (P < or = .01) compared with baseline during all treatment days in both treatment groups, with no statistically significant differences between treatments (median, -60.0 vs -59.5; P = .67). CONCLUSIONS: Both treatments led to significant improvements in NPIF, but the improvement was greater with the intranasal corticosteroid. Both treatments improved quality of life and reduced symptoms. The difference between the objective and subjective outcomes probably reflects the small sample size, the low pollen counts for the season, and the greater variability in subjective compared with objective measures.

Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis.

BACKGROUND: Antihistamine-decongestant combinations are used routinely for the treatment of seasonal allergic rhinitis. Recently, the combination of an antihistamine and a leukotriene receptor antagonist has been shown to be efficacious. OBJECTIVE: To compare the 2 combinations in the treatment of seasonal allergic rhinitis. METHODS: This was a randomized, double-blind, double-dummy, parallel study in which patients with seasonal allergic rhinitis received either fexofenadine, 60 mg, and pseudoephedrine, 120 mg, twice daily, or loratadine, 10 mg, and montelukast, 10 mg, once daily, for 2 weeks. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed at the beginning and end of the study. Patients recorded nasal symptoms and measured nasal peak inspiratory flow (NPIF) twice daily. Baseline measurements were obtained before initiation of treatment. RESULTS: Compared with baseline, both treatments resulted in statistically and clinically meaningful reductions of overall and individual RQLQ domain scores (P < .01) except for the sleep domain, for which only loratadine-montelukast led to significant improvement. There was a significant reduction in total symptoms (P < or = .05) compared with baseline on most treatment days in patients receiving both combinations. When the change from baseline was analyzed, there were no statistically significant differences in total symptoms between fexofenadine-pseudoephedrine and loratadine-montelukast (median, -28.5 vs -22.5; P = .33). There was a significant improvement in NPIF from baseline on all treatment days in both groups (P < .05), with no significant difference between treatments. CONCLUSIONS: Fexofenadine-pseudoephedrine and loratadine-montelukast have comparable efficacy in improving symptoms, RQLQ scores, and nasal obstruction in seasonal allergic rhinitis. The lack of improvement in sleep in the fexofenadine-pseudoephedrine group is probably related to insomnia, a known adverse effect of pseudoephedrine.

Elevation of the nasal mucosal surface temperature after warming of the feet occurs via a neural reflex.

OBJECTIVE: To evaluate in humans the mechanisms underlying the increase in nasal mucosal temperature following immersion of the feet in warm water (42 degrees C). MATERIAL AND METHODS: The nasal mucosal temperature of subjects was measured whilst their feet were immersed in warm water. RESULTS: The nasal mucosal temperature rose quickly on immersion and dissipated equally fast on removal of the feet from warm water. Intranasal lidocaine raised the mucosal temperature slightly after application, but also blocked the feet warming-induced increase in nasal mucosal temperature, suggesting a neural reflex. Whereas the cutaneous-nasal reflex stimulates a transient parasympathetic response, acetylcholine does not seem to contribute to the more prolonged increase in nasal mucosal temperature following immersion of the feet in warm water. Warming of the feet probably leads to a loss of alpha-sympathetic activity of nasal blood vessels and an increase in nasal mucosal temperature because application of phenoxybenzamine, an alpha-sympathetic blocking agent, to the nasal mucosa increased the nasal mucosal temperature. CONCLUSIONS: Our data suggest that the increase in nasal mucosal temperature after warming of the feet is mediated by a neural reflex, which is caused by loss of sympathetic activity of the nasal vasculature and a possible additional contribution of a long-acting parasympathetic mediator.

Fluticasone nasal spray and the combination of loratadine and montelukast in seasonal allergic rhinitis.

OBJECTIVE: 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. DESIGN: A 2-week, parallel, randomized, double-blind, double-dummy study with rolling enrollment. SETTING: 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. MAIN OUTCOME MEASURES: Questionnaire answers, daily nasal symptom scores, eosinophil counts, and ECP levels. RESULTS: 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. CONCLUSION: Both treatments provided clinically meaningful responses, but the overall results favored fluticasone propionate.

Effects of fexofenadine on the early response to nasal allergen challenge.

BACKGROUND: Previous studies using nasal allergen challenge models have shown that terfenadine, an H1 antihistamine, inhibits histamine release during the early response to allergen provocation. Fexofenadine, the active metabolite of terfenadine, has strong H1-antihistaminic activity and no cardiac effects. Clinical studies have documented the efficacy of fexofenadine in the treatment of allergic rhinitis. OBJECTIVE: To determine whether fexofenadine, like terfenadine, inhibits histamine and tryptase release during the early allergic response. METHODS: Randomized, double blind, placebo-controlled, two-way crossover study in 20 subjects with seasonal allergic rhinitis, out of their allergy season (median age 27.5 years, 13 males and 7 females). Subjects were medicated with either placebo or fexofenadine 180 mg orally daily for 1 week followed by nasal challenge with allergen. After each challenge, sneezes and nasal symptoms were recorded, and a nasal lavage was obtained for the assay of albumin, an indicator of vascular permeability, and histamine and tryptase, indicators of mast cell degranulation. RESULTS: When patients were on placebo, allergen challenges led to significant increases in all measured parameters compared with the sham challenges with diluent. Treatment with fexofenadine resulted in inhibition of allergen-induced symptoms and increased vascular permeability, but not the release of histamine and tryptase. CONCLUSION: Fexofenadine is an effective H1 antihistamine, but in contrast to its parent compound, terfenadine, it does not affect the release of the mast cell mediators histamine and tryptase.

Effects of intranasal azelastine on the response to nasal allergen challenge.

OBJECTIVES/HYPOTHESIS: Azelastine, a second-generation H1-receptor antagonist, is available for topical administration. The aim of the study was to evaluate the effects of topical intranasal azelastine on the early-phase and the late-phase allergic responses and on nasal hyper-responsiveness to methacholine. STUDY DESIGN: Double-blind, placebo-controlled, two-way crossover study in 20 subjects with seasonal allergic rhinitis, out of their allergy season. METHODS: Subjects were randomly assigned to receive either placebo or two puffs of azelastine twice a day (548 microg/d) for 2 weeks followed by nasal challenge with allergen. Twenty-four hours later, while still receiving treatment, subjects underwent a nasal lavage and a nasal challenge with methacholine. End points included symptom scores, levels of mediators and number of eosinophils in nasal lavages, and the weight of secretions after methacholine challenge. RESULTS: Compared with placebo, treatment with intranasal azelastine resulted in significant reductions in allergen-induced sneezing, rhinorrhea, itching, nasal congestion, and levels of albumin during the early-phase response (P <.05). Azelastine had no effect on levels of histamine or tryptase during the early-phase response. There was a significant eosinophil influx 24 hours after challenge, which was not inhibited by azelastine. Treatment with azelastine had no effect on the levels of albumin, interleukin-4, interleukin-5, intercellular adhesion molecule-1, tumor necrosis factor-alpha, and eosinophil cationic protein during the late-phase response. However, azelastine did show a significant inhibitory effect on the methacholine response 24 hours after nasal allergen challenge (P <.05). CONCLUSIONS: The effects of intranasal azelastine are similar to those of oral second-generation antihistamines.