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PubMed1986

Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans.

The possible role of leukotriene D4 (LTD4) in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose-response related increase in nasal mucosal blood flow as measured by laser-Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose-related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose-related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.

Administration, Topical↗
PubMed1985

Nasal challenge with serotonin and histamine in normal persons.

In order to study the nasal response to serotonin, 14 normal persons, in a double-blind study, were provoked in the nose with serotonin and histamine. Itching and the number of sneezes were noted, the amount of secretion measured, and nasal airway resistance recorded by active posterior rhinomanometry. Serotonin induced significant nasal itching, sneezing and hypersecretion, similar to the effects of histamine. The effect of serotonin on nasal airway resistance, on the other hand, was slight (+ 10%) and insignificant in contrast to that of histamine in equipotent doses (+ 48%) (P less than 0.001). In conclusion, we have shown that serotonin provocation can induce a rhinitis response in the human nose. The nasal symptoms suggest an effect on sensory nerves with reflex-induced sneezing and hypersecretion, while there appears to be little direct effect on capacitance vessels. The possible role of serotonin as a mediator of rhinitis remains speculative.

Adolescent↗
PubMed1988

Effect of topical levocabastine on allergic and non-allergic perennial rhinitis. A double-blind study, levocabastine vs. placebo, followed by an open, prospective, single-blind study on beclomethasone.

Forty-four patients, with symptoms of nasal obstruction, sneezing, itching and/or rhinorrhea, were entered into a placebo-controlled, double-blind study to evaluate the clinical efficacy of a topical antihistamine drug, levocabastine, applied 4 times a day for 14 days. At the end of the treatment the placebo patients were treated with levocabastine and the levocabastine patients were treated with beclomethasone dipropionate in a single-blind design for another 14 days. This study showed that levocabastine is significantly more active than placebo with reference to nasal discharge and sneezing. Placebo application improved the symptom score. Levocabastine could not be proved to be more effective against nasal obstruction than placebo in the double-blind trial. In the single-blind set-up, levocabastine resulted in an additional improvement in the score for obstruction, after the placebo period. Although the allergic group tended to respond better, no statistically significant difference could be detected between allergic and non-allergic patients. After treatment with levocabastine, beclomethasone dipropionate administration could not improve the results for nasal discharge and sneezing. For nasal congestion, beclomethasone dipropionate proved to be superior to levocabastine.

Administration, Intranasal↗
PubMed1994

Efficacy of acrivastine in the treatment of allergic rhinitis during natural pollen exposure: onset of action.

In a placebo-controlled, randomized, and double-blind 1-day field study, the efficacy and onset of action of capsule acrivastine 8 mg were evaluated in 42 patients suffering from allergic rhinoconjunctivitis elicited by natural grass pollen exposure. Before and for 2 h after treatment, the patients scored the severity of five rhinoconjunctivitis symptoms every 10 min on a 0-5 scale (0 = no symptoms; 5 = very severe symptoms). The number of sneezes was recorded, and every 30 min, measurements of nasal peak flow were made. Before treatment, there was no difference in median total symptom score (mTSS) between the acrivastine group (A) and the placebo group (P) (12 and 12, respectively). Time of onset was estimated by an exponential decay model to be 19 min (95% confidence interval 0-39 min). A statistically significant difference in percent reduction of mTSS between A and P was observed for the first time 46 min after treatment start (A = 22%, P = 0%, P < 0.05). A 50% reduction in total symptom score (TSS) was achieved within 60 min by 38% in A and 17% in P (NS), and within 80 min in 52% and 17%, respectively (P < 0.05). The median time for 50% reduction in TSS (MT50) was 80 min for A and > 120 min for P (P < 0.01). The symptom score of sneezing and number of sneezes were evaluated for periods of 30 min. The difference between A and P became statistically significant from 31-60 and 61-90 min, respectively (P < 0.05 and P < 0.01). Objective and subjective determinants in the different time intervals were well correlated. Improvement of nasal congestion was observed in A at 91-120 min, as measured by nasal peak flow.

Administration, Oral↗
PubMed1995

The effect of cetirizine on sulfidoleukotriene production by blood leukocytes in children with allergic rhinitis.

Twelve children with allergic rhinitis due to monosensitivity to Dermatophagoides pteronyssinus (Dp) took part in a placebo-controlled, double-blind, crossover study to evaluate the effect of cetirizine, a second-generation, nonsedating H1-blocker-type antihistamine, on sulfidoleukotriene releasability by blood leukocytes and to determine its correlation with clinical findings and nasal challenge scores. Sulfidoleukotriene release by blood leukocytes was determined by the cellular allergen stimulation test (CAST), which measures leukotriene (LT)C4, LTD4, and LTE4, all in one assay. Compared to placebo, cetirizine significantly (P < 0.05) decreased daily symptom scores of nasal discharge, nasal itching, and sneezing, as well as the number of sneezings after nasal challenge with the antigen, without alleviating nasal obstruction (P > 0.05). It also suppressed both early (P < 0.05) and late skin reactions to intradermal tests. Although cetirizine did not influence in vitro sulfidoleukotriene production by blood leukocytes with buffer or anti-IgE (P > 0.05), it substantially reduced the release of these mediators upon challenge with Dp antigen. Furthermore, there was a high correlation between the number of sneezes after challenge and the amount of sulfidoleukotriene released in nine patients (r = 0.78; P < 0.01). It is concluded that the amount of sulfidoleukotrienes produced by blood leukocytes in vitro may reflect the nasal hyperreactivity of the patient, and that cetirizine, which is highly effective in the treatment of allergic rhinitis, owes part of its effect to inhibition of sulfidoleukotriene releasability by blood leukocytes in children.

Adolescent↗
PubMed1998

Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials.

OBJECTIVE: To determine whether intranasal corticosteroids are superior to oral H1 receptor antagonists (antihistamines) in the treatment of allergic rhinitis. DESIGN: Meta-analysis of randomised controlled trials comparing intranasal corticosteroids with oral antihistamines. SETTING: Randomised controlled trials conducted worldwide and published between 1966 and 1997. SUBJECTS: 2267 subjects with allergic rhinitis in 16 randomised controlled trials. MAIN OUTCOME MEASURES: Nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, nasal discomfort, total nasal symptoms, nasal resistance, and eye symptoms and global ratings. Outcomes measured on different scales were combined to determine pooled odds ratios (categorical outcomes) or standardised mean differences (continuous outcomes). Assessment of heterogeneity between studies, and subgroup analyses of eye symptoms, were undertaken. RESULTS: Intranasal corticosteroids produced significantly greater relief than oral antihistamines of nasal blockage (standardised mean difference 0.63, 95% confidence interval - 0.73 to - 0.53), nasal discharge (-0.5, - 0.6 to - 0.4), sneezing (- 0.49, - 0.59 to - 0.39), nasal itch (- 0.38,- 0.49 to - 0.21), postnasal drip (- 0.24,- 0.42 to - 0.06), and total nasal symptoms (- 0.42,- 0.53 to - 0.32), and global ratings gave an odds ratio for deterioration of symptoms of 0.26 (0.08 to 0.8). There were no significant differences between treatments for nasal discomfort, nasal resistance, or eye symptoms. The effects on sneezing, total nasal symptoms, and eye symptoms were significantly heterogeneous between studies. Other combined outcomes were homogeneous between studies. Subgroup analysis of the outcome of eye symptoms suggested that the duration of assessment (averaged mean score over the study period versus mean score at end of study period) might have accounted for the heterogeneity. CONCLUSION: The results of this systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis.

Administration, Intranasal↗
PubMed2000

Effect of mometasone furoate by topical application on allergic rhinitis model in rats.

The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect.

Administration, Topical↗
PubMed1993

Effect of terfenadine on nasal provocation.

The effect of premedication with terfenadine, an H1 antagonist, on nasal challenge with antigen, histamine and methacholine was evaluated. A single dose of terfenadine had no effect on the response to a localized challenge with methacholine but completely blocked the secretory response to histamine on both the ipsilateral and contralateral sides. These results suggest that terfenadine has no anticholinergic activity and that the direct and reflex secretory response to challenge with histamine is mediated by the H1 receptor. A single dose of terfenadine significantly reduced sneezing and nasal secretion after challenge with antigen but had no effect on nasal congestion. A double-blind placebo-controlled clinical trial was undertaken to compare the effects of pretreatment with terfenadine for 1 week on the response to sequential nasal challenge with antigen and histamine. Terfenadine significantly reduced the number of sneezes and the levels of kinins, albumin and TAME esterase activity following challenge with antigen. The levels of histamine were also significantly reduced, suggesting inhibition of the degranulation of mast cells. The number of sneezes and the levels of albumin were also significantly reduced by terfenadine following challenge with histamine.

Humans↗
PubMed1993

The influence of terfenadine and pseudo-ephedrine alone and in combination on allergen-induced rhinitis.

Nasal biopsies to naturally occurring allergic rhinitis demonstrate ultrastructural evidence of mast cell degranulation. Consistent with this, H1 antihistamines are clinically efficacious in this disorder. The nasal symptoms of itch, sneeze and discharge are, however, more susceptible to this mode of therapy than is nasal blockage. As nasal blockage is vascular, the combination of an H1 antihistamine and a decongestant has a logical rationale. To investigate the efficacy of such a combination, the influence of pretreatment with terfenadine, 60 mg, pseudo-ephedrine, 120 mg, Seldane-d (a registered trademark of Marion Merrell Dow)--a combination of pseudo-ephedrine, 120 mg, and terfenadine, 60 mg,--and matched placebo was objectively investigated on the nasal response to allergen in grass-pollen-sensitive seasonal rhinitic subjects (7 males, 7 females, age 19-56 years) in a double-blind, placebo-controlled, 4-period cross-over study. Seldane-D was significantly better than placebo in all efficacy measurements: nasal itch (p < 0.02), sneezing (p < 0.01), discharge (p < 0.01) and blockage (p < 0.003). The terfenadine component of Seldane-D contributed predominantly to the reduction in itch, sneeze and discharge (p < 0.01) while the pseudo-ephedrine component primarily contributed to the nasal airway effects (p < 0.04). These results indicate that the combination of terfenadine and pseudo-ephedrine as a single oral medication is complementary.

Adult↗
PubMed1995

Effects of intranasal administration of endothelin-1 to allergic and nonallergic individuals.

Endothelin-1 (ET-1), a 21 amino acid peptide, and its receptors are distributed in the mammalian respiratory tract. To examine the responses of human upper airways to ET-1, we investigated the effects of intranasal administration of ET-1 to nine symptomatic allergic and nine nonallergic volunteers. Paper discs were used to administer ET-1 or diluent to one side of the nasal mucosa, and to collect secretions from the ipsilateral (challenged) and contralateral (opposite) nostrils. ET-1 (0.3-10 micrograms), but not diluent, induced dose-dependent bilateral increases in secretion weights, lysozyme secretion, symptoms of rhinorrhea and itch, and sneezing in both populations. ET-1 did not induce albumin secretion, histamine release, or symptoms of nasal congestion. Compared with the nonallergic subjects, allergic individuals sneezed more and had significantly higher bilateral secretion weights, contralateral lysozyme secretion, and symptoms of rhinorrhea following ET-1 provocation. In summary, ET-1 induced symptoms relevant to inflammatory upper airway diseases in allergic and nonallergic subjects. However, responses of allergic subjects were more pronounced, particularly with respect to symptoms associated with neural reflex responses, such as sneezing and contralateral secretion. Therefore, allergic inflammation enhances responsiveness of the nasal mucosa to ET-1.

Administration, Intranasal↗
PubMed2005

Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms relative to placebo in two studies involving subjects with allergic conjunctivitis or rhinoconjunctivitis.

BACKGROUND: A new formulation of olopatadine hydrochloride ophthalmic solution (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled, double-masked, hybrid environmental studies intended to determine efficacy and safety in subjects with histories of seasonal allergic conjunctivitis or rhinoconjunctivitis. DESIGN AND METHODS: In these 10- and 12-week trials (conducted April-August 2003 and July-December 2001, respectively), subjects assessed their ocular signs and symptoms. Additionally, subjects in the 10-week trial evaluated the frequency of their nasal symptoms while subjects in the 12-week trial evaluated both the frequency and severity of their nasal symptoms. The two trials had a combined enrollment of 500 subjects (217 males, 283 females) including 44 children aged 10-17 years; the combined population was 81.4% Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these studies, either ragweed (fall study) or grass (spring study) pollen counts were obtained from each investigative center. Slope analyses were conducted on the nasal symptom assessments by pollen count. RESULTS: The nasal results from the two clinical trials are presented herein. In the fall study, relative to placebo, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031) relative to placebo. In the fall trial, 2 subjects discontinued due to treatment-related adverse events (tachycardia and dry eye), while in the spring study, no subject discontinued due to a treatment-related adverse event. No subject in either study suffered a treatment-related serious adverse event. CONCLUSIONS: For the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe, well-tolerated, and effective in significantly reducing the frequency and/or severity of some effects of pollen on nasal symptoms.

Adolescent↗
PubMed2003

[Studies on the experimental allergic rhinitis induced by Japanese cedar pollen--role of cysteinyl leukotrienes in nasal allergic symptoms].

Cysteinyl leukotrienes (CysLTs: LTC4, LTD4, and LTE4) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. Because treatment with a CysLT1 receptor antagonist and a 5-lipoxygenase inhibitor modified allergen-induced nasal blockage in patients with allergic rhinitis, and CysLTs were detected in nasal cavity lavage fluid, it has been suggested that CysLTs act as significant inflammatory mediators in allergic rhinitis. The role of CysLTs was evaluated in our experimental allergic rhinitis model in sensitized guinea pigs which shows biphasic nasal blockage, sneezing and nasal hyperresponsiveness to LTD4 induced by repetitive inhalation challenge with Japanese cedar pollen. In this model, the CysLT1 receptor antagonist pranlukast suppressed the late-phase nasal blockage but not early blockage and sneezing. Nasal hyperresponsiveness (nasal blockage) to LTD4 was largely blocked by pranlukast, naphazoline, and N omega-nitro-L-arginine-methyl ester. The results demonstrate that nasal blockage induced by CysLTs is mainly due to dilatation of nasal blood vessels, which can be induced by the nitric oxide produced through CysLT1 receptor activation. On the other hand, when pollen inhalation challenge was performed in the presence of nasal hyperresponsiveness, antigen-induced biphasic nasal blockage and sneezing were considerably enhanced and CysLTs contributed to both symptoms, suggesting that nasal hyperresponsiveness induces aggravation of antigen-induced nasal symptoms. The results presented in this study further suggest that our model is a good representative of human allergic rhinitis and offer evidence that CysLTs are chemical mediators mainly responsible for allergic nasal symptoms.

Allergens↗
PubMed2001

Efficacy of nimesulide alone and in combination with cetirizine in acute allergic rhinitis.

OBJECTIVE: To study the effect of cetirizine and nimesulide given alone and in combination in allergic rhinitis. METHOD: A double blind, double dummy, randomised, parallel controlled clinical study in three groups consisting of 18 patients each suffering from allergic rhinitis was conducted. Group A was given nimesulide alone (100 mg BD), Group B received combination (nimesulide 100 mg + cetirizine 10 mg) and Group C was given cetirizine alone (10 mg) for one week. The efficacy of each treatment in reducing nasal stuffiness, nasal discharge, itching nose and watery eyes was assessed at base line (day 0), on days four and eight of treatment. Patients used diary cards twice daily to rate symptom severity on a four point scale. RESULTS: Nimesulide and cetirizine alone could decrease nasal discharge, nasal stuffiness and sneezing significantly in allergic rhinitis patients by day four. Cetirizine was more effective in relieving nasal discharge and sneezing compared to nimesulide. By combining cetirizine and nimesulide four symptoms of allergic rhinitis, i.e., nasal discharge, nasal stuffiness, sneezing and watery eyes decreased significantly. CONCLUSION: Present study has shown that nimesulide alone could decrease three symptoms of allergic rhinitis like certirizine and combination of cetirizine (anti-histaminic) and nimesulide (anti-inflammatory) exerts synergistic action in reducing symptoms in patients of allergic rhinitis.

Adolescent↗
PubMed2005

Radiofrequency for the treatment of vasomotor rhinitis.

OBJECTIVES: We assessed the efficacy of submucosal application of radiofrequency to the inferior turbinate for the treatment of vasomotor rhinitis. PATIENTS AND METHODS: Twenty patients with vasomotor rhinitis (9 males, 11 females; mean age 29.2 years; range 20 to 40 years) were treated with radiofrequency applied to the inferior turbinate. Symptoms such as nasal obstruction, sneezing, and watery nasal discharge were graded with the use of a visual analog scale (VAS) before, and on days 1, 3, 7, 30, 60, 90, and 180 after the treatment. RESULTS: The severity of symptoms began to decrease following the first week after the application. Maximum relief was achieved between 30 to 60 days after the intervention. The highest rate of improvement (85.4%) was reported in sneezing, followed by nasal obstruction (76.4%) and nasal discharge (67.7%). The mean VAS scores showed a significant improvement in all symptoms between 7 to 180 days after the procedure (p<0.05). The rate of patient satisfaction was 90% for the relief of nasal obstruction and sneezing, and 80% for nasal discharge. Complaints about vasomotor rhinitis increased up to a severity near the pretreatment level in eight patients on the 180th postoperative day and the procedure was repeated. CONCLUSION: These findings indicate that radiofrequency may be used as an alternative treatment option in patients with vasomotor rhinitis.

Adult↗
PubMed2006

Clinical effects of apple polyphenols on persistent allergic rhinitis: A randomized double-blind placebo-controlled parallel arm study.

BACKGROUND: We often encounter persistent allergic rhinitis due to house dust mites in the practice of otolaryngology, and its prevalence in Japan is high (18.7%). Persistent allergic rhinitis is usually treated with antihistamines and local steroids, but they often cause adverse effects such as sedation and drowsiness. Polyphenols derived from apples have been reported to suppress histamine release from rat cells, reduce auricular swelling in allergic mice, and alleviate skin inflammation in atopic patients. These effects suggest that apple polyphenols are effective for the treatment of various allergic disorders, but the results of their clinical use have not been reported. OBJECTIVE: To assess the effect of drinks containing apple polyphenols on clinical symptoms of persistent allergic rhinitis. METHODS: Thirty-three patients aged 15 to 65 years with moderate or severe persistent allergic rhinitis in whom the symptoms persisted for 3 years or longer were treated without apple polyphenols (control group), with a low dose of apple polyphenols, or with a high dose of apple polyphenols, and changes in the clinical symptoms were examined. RESULTS: Significant improvements were observed in sneezing attacks (P<.05) and nasal discharge (P<.01) in the high-dose group and in sneezing attacks (P<.05) in the low-dose group. Compared with the control group, an improvement was observed in sneezing attacks and nasal discharge in many patients of the polyphenol-treated groups. In terms of intranasal findings, a significant improvement was observed in swelling of the nasal turbinate in the low-dose group (P<.05). The percentage of patients who showed an improvement in swelling of the nasal turbinate was higher in the polyphenol-treated groups. CONCLUSIONS: We conclude that apple polyphenols are effective in alleviating symptoms of persistent allergic rhinitis.

Adult↗
PubMed1993

Effects of antihistamines on inflammatory mediators.

The nasal antigen challenge model has proved useful in assessing the roles of inflammatory mediators in the clinical allergic response. Studies using this model have revealed that the acute allergic response is associated with increased concentrations of histamine, prostaglandin D2 (PGD2), leukotrienes, tryptase, and kinins, and with increased TAME-esterase activity. The effects of antihistamines on the clinical response and inhibition of mediator release have also been examined with this model. Premedication with terfenadine caused a marked reduction in sneezing as well as decreased histamine release, kinin levels, and TAME-esterase activity. Levels of PGD2 also decreased, although not significantly. Release of leukotriene C4 (LTC4) was not affected by this agent. Terfenadine also reduced vascular permeability as reflected in decreased albumin levels. In this model, cetirizine reduced sneezing, TAME-esterase activity, and albumin levels, whereas histamine release and PGD2 levels remained unaffected. Pretreatment with cetirizine resulted in significantly reduced levels of LTC4. Loratadine markedly, but not significantly, inhibited the sneezing response and reduced release of histamine, PGD2, and LTC4. Albumin and kinin levels were significantly diminished. The clinical significance of the inhibitory effects of antihistamines on mediator release has yet to be determined.

Cetirizine↗
PubMed1995

[The effect of KW-4679, an antiallergic drug, on experimental allergic rhinitis].

Effect of KW-4679, an antiallergic agent, on the experimental allergic rhinitis was studied in guinea pigs. 1) KW-4679 inhibited the sneeze response and the nasal rubbing induced after the intranasal administration of antigen in sensitized guinea pigs. The inhibitions were dose-related and significant at 0.03 mg/kg p.o. for sneeze response and 1 mg/kg p.o. for nasal rubbing, respectively. 2) The nasal vascular permeability was increased after the intranasal administration of antigen in sensitized guinea pigs. KW-4679 significantly reduced the increase of the nasal vascular permeability at 1 mg/kg p.o. or higher. From these results, KW-4679 may have inhibitory effects on sneeze, nasal irritation and rhinorrhea in clinical use.

Animals↗
PubMed1987

Arachidonic acid metabolites during nasal challenge.

In order to assess the role of arachidonic acid metabolites in the early reaction to antigen, we challenged six allergic individuals with and without premedication with aspirin and recorded their clinical response, as indicated by number of sneezes, and measured the levels of inflammatory mediators. The early reaction to antigen was associated with increases in the levels of histamine, N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity, prostaglandin (PG) D2, leukotriene C4, PGE, and thromboxane. Aspirin significantly inhibited the increases in the cyclooxygenase metabolites PGE, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane but did not affect the amount of sneezing or the levels of histamine, TAME-esterase activity, or leukotrienes. The pattern of the metabolites and their response to pretreatment with aspirin parallel the response of purified human lung mast cells, supporting the notion that the early phase of allergic rhinitis is a mast cell-dominated event.

6-Ketoprostaglandin F1 alpha↗