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PubMed2006

Interactive effect of histamine and prostaglandin D2 on nasal allergic symptoms in rats.

This study was undertaken to investigate the interactive effect of histamine and prostaglandin D(2) in nasal allergic symptoms in rats. The intranasal application of histamine at doses lower than 10 mumol/site caused no sneezing or nasal rubbing. In addition, prostaglandin D(2) also showed no significant increase in these responses, even at a dose of 10 nmol/site. On the other hand, the simultaneous instillation of histamine and prostaglandin D(2) resulted in a 1000 times more potent effect in inducing nasal symptoms than the administration of histamine alone. Thus, prostaglandin D(2) enhanced the actions of histamine in inducing sneezing and nasal rubbing in a dose-dependent manner, and significant effects were observed at doses higher than 1 nmol/site. The responses induced by the simultaneous application of histamine and prostaglandin D(2) were inhibited by chlorpheniramine, cyproheptadine, BW A868C and ramatroban. Chlorpheniramine and cyproheptadine showed the dose-related inhibition of nasal symptoms induced by the combined administration of histamine (10 nmol) and prostaglandin D(2) (10 nmol), but the effect of cyproheptadine was relatively weak compared with chlorpheniramine. Moreover, BW A868C and ramatroban also showed the inhibition of nasal symptoms induced by the simultaneous administration of histamine and prostaglandin D(2) in a dose-dependent manner. BW A868C was more potent in inhibiting the nasal symptoms than ramatroban. These results clearly indicate that prostaglandin D(2) showed a synergistic effect on sneezing and nasal rubbing induced by histamine in rats, and its effect occurred through both prostaglandin D(2) and CRTH2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) receptors.

Administration, Intranasal↗
PubMed2000

A new model of allergic rhinitis in rats by topical sensitization and evaluation of H(1)-receptor antagonists.

An animal model of chronic allergic rhinitis was developed by repeated local booster sensitization into the nasal cavity in sensitized rats. The severity of allergic rhinitis was assessed by determining the extent of two markers of nasal allergic symptoms (sneezing and nasal rubbing) after antigen challenge. The number of incidents of sneezing and nasal rubbing was markedly increased during intranasal instillation of antigen in sensitized rats. The PCA titers were also markedly elevated by intranasal sensitization. Some histamine H(1)-receptor antagonists such as chlorpheniramine, ketotifen, astemizole and epinastine inhibited the increase in antigen-induced nasal symptoms in a dose-related manner. Nasal rubbing was more potently inhibited by H(1)-receptor antagonists than sneezing. In conclusion, we developed a chronic allergic rhinitis model showing nasal symptoms in rats, and this model may be useful for evaluating the effects of drugs on allergic rhinitis.

Allergens↗
PubMed1980

Treatment of allergic and vasomotor rhinitis by the local application of silver nitrate.

A new, simple and effective local treatment of allergic and vasomotor rhinitis is presented. Using 15 per cent silver nitrate, bilateral chemical cautery of the anterior part of the nasal septum and inferior turbinates has been carried out at weekly intervals on 1 to 5 occasions, in 41 cases. No distinction was made between allergic rhinitis and vasomotor rhinitis. 92.6 per cent of cases belonged to the age group of 11 to 50 years. There was a slight predominance of female over male patients in this study. Only those cases were selected who had sneezing as the presenting symptom, while 17 per cent of these patients also suffered from asthma. The eosinophil count in the blood was below 5 per cent in 73.2 per cent of cases, and was above 10 per cent in 9.8 per cent of cases. Eosinophils were present in the nasal secretions of of 66.6 per cent of patients. Intestinal parasites were detected in the stools of 19.5 per cent of cases. No significant quantity of methaemoglobin was detected in the blood of any patient. Silver nitrate was applied after topical anaesthesia with 4 per cent lignocaine solution. The majority of patients had 2 to 4 applications. 68.3 per cent of patients had good relief, particularly from sneezing and watering of the nose. If patients treated with only a single application of silver nitrate are excluded from the series, 79.4 per cent patients reported relief. Significantly, out of 7 cases who were suffering from allergic rhinitis as well as asthma, 57.1 per cent of cases had freedom from the asthma. Among 3 patients who had no relief with earlier intranasal hydrocortisone injections, 66.6 per cent cases had good relief with silver nitrate. One patient who had good relief from allergic rhinitis developed anosmia after this treatment and some patients experienced transient sneezing and rhinorrhoea after the application of silver nitrate. Long-term results are awaited and it is suggested that further studies are necessary regarding the number of applications, the interval between applications, the strength of the silver nitrate solution, and the possible use of other chemical or physical agents for this mode of treatment.

Administration, Topical↗
PubMed1997

Efficacy of brompheniramine maleate for the treatment of rhinovirus colds.

We tested the efficacy of brompheniramine maleate in a large randomized, controlled trial of volunteers with experimental rhinovirus colds. Brompheniramine (12 mg) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms (24, 36, or 48 hours after virus challenge). During the first 3 days of treatment (the first 4 days after virus challenge), nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine (n = 113) than for controls (day 1: 4.3 g vs. 6.8 g; day 2: 4.8 g vs. 7.7 g; and day 3: 3.3 g vs. 5.3 g) (P < or = .03), as were rhinorrhea scores (day 1: 0.6 vs. 0.8; day 2: 0.5 vs. 0.8; and day 3: 0.3 vs. 0.5) (P < .03), sneeze counts (day 1: 1.8 vs. 3.6; day 2: 2.1 vs. 5.1; and day 3: 1.3 vs. 3.3) (P < or = .001), and sneeze severity scores (day 1: 0.3 vs. 0.6; day 2: 0.25 vs. 0.7; and day 3: 0.2 vs. 0.4) (P < .001) (n = 112). Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls (4.7 vs. 7.9) (P = .05) (day 2 after virus challenge), and other symptoms were modestly reduced or were unaffected in the brompheniramine group. Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 (4.8 vs. 6.0) (P = .03) and 2 (4.1 vs. 5.6) (days 2 and 3 after virus challenge) (P = .003). Treatment with brompheniramine was associated with the adverse effects of somnolence (n = 3) and confusion (n = 1). Brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds.

Adolescent↗
PubMed1992

The effect of azelastine on the early allergic response.

To study the effect of azelastine on the immediate reaction to nasal allergen challenge, we performed a double blind, placebo-controlled cross-over clinical trial. Thirteen subjects with seasonal allergic rhinitis underwent nasal challenge with antigen 4 hr after a single oral 2 mg dose of azelastine. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, immunoreactive sulphidopeptide leukotrienes, kinis and TAME-esterase activity in recovered nasal lavages. After a single dose of azelastine, there was a significant reduction in sneezing (10 vs 2, P = 0.01) and in the median levels of recovered TAME-esterase activity (63.1 vs 17.5 c.p.m. x 10(-3), P = 0.01), immunoreactive sulphidopeptide leukotrienes (7.5 vs 2.1 ng/ml, P = 0.03) and kinins (1370 vs 251 pg/ml, P = 0.03), with no significant reduction in the median levels of histamine (3.7 vs 1.2 ng/ml, P = 0.2) and prostaglandin D2 (70 vs 70 pg/ml, P = 0.2) compared to placebo (numbers represent total increase over diluent challenge). These results suggest that azelastine does not inhibit mast cell activation but affects the consequences of released histamine, namely sneezing, increased vascular permeability and the generation of kinins. The results further suggest that other cells, in addition to mast cells, might be responsible for the generation of leukotrienes during the early allergic response, and that azelastine reduces their ability to generate this mediator or that inhibition of leukotriene release from mast cells occurs at lower drug concentrations.

Adult↗
PubMed1994

Defensive reflexes of the respiratory system in anaesthetized rabbits during high frequency jet ventilation.

The defensive airway reflexes during high frequency jet ventilation (HFJV) were studied in anaesthetized, non-vagotomized (n = 16) and vagotomized (n = 11) rabbits. The animals were ventilated by a high frequency jet ventilator. Sneezing and coughing were evoked by mechanical stimulation of the airways. During HFJV spontaneous breathing was inhibited only in the non-vagotomized rabbits. Mechanical stimulation of the airways during HFJV evoked sneezing and coughing, in which the inspiratory component was inhibited. This inhibition occurred not only in defensive reflexes evoked from the regions with increased pressure (trachea, bronchi), but also from the nose. Vagotomy diminished but did not fully eliminate the changes in sneezing accompanying HFJV. The intensity of maximum expiratory efforts was not significantly affected by HFJV in both subgroups.

Animals↗
PubMed1988

Lung C-fibre receptor activation and defensive reflexes in anaesthetized cats.

1. With pentobarbitone-anaesthetized cats we have elicited cough reflexes from the tracheobronchial tree and the larynx, and the aspiration and sneeze reflexes from the nasopharynx and the nose respectively. The reflexes were induced by mechanical stimulation of the mucosa, before and during activation of pulmonary C-fibre receptors by intravenous injections of capsaicin or phenylbiguanide. 2. During the 20-30 s apnoea due to C-fibre stimulation, the cough reflex from both sites and the sneeze reflex were completely abolished, whereas the aspiration reflex response was approximately halved. Reflex contractions of genioglossus muscle still occurred at this time, but were far weaker than in the control state. 3. During the rapid shallow breathing that immediately followed apnoea due to C-fibre receptor stimulation, the defensive reflexes recovered: the aspiration and sneeze reflexes fully and the cough reflexes to about half of the control response. 4. Acute hypotension due to haemorrhage, of a size considerably greater than that due to stimulation of the pulmonary C-fibre receptors, caused no significant inhibition of the cough reflex from the tracheobronchial tree. 5. We conclude that the pulmonary C-fibre reflex powerfully inhibits airway defensive reflexes, and that its activation is unlikely to contribute positively to coughing induced by aerosols of capsaicin and similar agents.

Action Potentials↗
PubMed1998

Asymmetry in reflex responses of nasal muscles in anesthetized guinea pigs.

Nasal reflexes elicited by mechanical or electrical stimulation of nasal afferents were studied in anesthetized guinea pigs. Probing the nasal cavity of one side evoked a greater activation of the contralateral than the ipsilateral nasal muscles and, occasionally, sneezing. Similarly, electrical stimulation of the ethmoidal nerve often caused sneezing, with a greater activation of the nasal muscles and a greater increase in resistance on the contralateral side. Asymmetrical activation of the nasal muscles in response to mechanical stimuli induces asymmetrical airflows, especially during sneezing, between the two sides of the nasal cavity. Most of the expired air is forcibly blown out through the ipsilateral nostril, thus improving the elimination of irritants from the nose.

Airway Resistance↗
PubMed2000

Exposure to diesel exhaust aggravates nasal allergic reaction in guinea pigs.

Diesel exhaust particulates (DEP) () and exposure to diesel exhaust (DE) induce nasal mucosal hyperresponsiveness to histamine. Therefore, in the present study, we investigated whether or not exposing guinea pigs to DE aggravates the nasal allergic reaction induced by repeated nasal administration of ovalbumin (OVA). Guinea pigs were exposed to filtered air or to DE (DE containing 0.3 or 1.0 mg/m(3) of DEP) for 5 wk. During exposure to filtered air or to DE, guinea pigs were administered 1% of OVA in saline into the nasal cavities once a week. Sneezes were counted and nasal secretions were measured as indices of sneezing responses and rhinorrhea for 20 min after OVA administration. Titers of specific anti-OVA-IgG and anti-OVA-IgE and the number of eosinophils infiltrated into both nasal epithelium and subepithelium were measured at the end of the exposure to DE. Exposure to DE enhanced the number of sneezes and the amount of nasal secretions induced by OVA. Titers of specific anti-OVA-IgG and anti-OVA-IgE also significantly increased in DE-exposed animals. Exposure to DE also augmented the number of eosinophils that infiltrated both the nasal epithelium and the subepithelium induced by OVA. These results suggest that exposure to DE enhances the nasal allergic reaction induced by repeated antigen administration in guinea pigs.

Animals↗
PubMed1991

Antigen-provoked increase in histamine reactivity. Observations on mechanisms.

To investigate the effect of antigen provocation on nonspecific reactivity to histamine, nine allergic individuals underwent multiple nasal challenges with histamine, or antigen. The response to challenge was assessed by counting the number of sneezes and measuring the levels of albumin and TAME-esterase (TAME; [3H]N-alpha-tosyl-L-arginine methyl ester) activity in recovered nasal lavages. In the case of antigen, levels of histamine were also measured. In response to histamine, the subjects sneezed and had increased levels of albumin and TAME. The responses to antigen or histamine were unchanged 24 h after histamine provocation. The responses to histamine provocations were increased with respect to symptom scores and to the levels of TAME activity and albumin in nasal lavages compared to baseline challenge, however, 24 h after antigen provocation. Increasing antigen exposure from 1 to 3 days did not further increase the responsiveness to histamine. Histamine reactivity returned to baseline 12 days after antigen exposure. The number of eosinophils, neutrophils, and alcian blue-positive cells in the lavages after antigen challenge and before the histamine challenges correlated with the changes in response to histamine. The increase in sneezing induced by antigen stimulation correlated with the increase in the same parameter after histamine provocation 24 hr after antigen challenge (r = 0.88; p less than 0.01). Surprisingly, the other parameters assessed did not show similar correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Role of capsaicin-sensitive trigeminal nerves in development of hyperreactive nasal symptoms in guinea pig model of nasal allergy.

The effect of capsaicin pretreatment on frequency of sneezing, decrease of nasal patency, and increase of vascular dye leakage induced by antigen or histamine challenge on the guinea pig nasal mucosa was investigated. The animals were sensitized intraperitoneally with ovalbumin. Capsaicin pretreatment significantly inhibited sneezing induced by nasal challenge with histamine and antigen, indicating that capsaicin-sensitive sensory nerves constitute an afferent pathway of the sneezing reflex in nasal allergy. Although capsaicin pretreatment tended to inhibit the decrease of nasal patency and the increase of vascular dye leakage of the nasal mucosa induced by antigen challenge, this tendency was not statistically significant. The present study indicated that the participation of a local reflex via capsaicin-sensitive trigeminal nerves in nasal vascular responses observed after antigen challenge in the guinea pig model of nasal allergy is rather small compared to the large direct vascular effects of chemical mediators released from basophilic cells in the nasal mucosa.

Airway Resistance↗
PubMed2001

Comparison of cedar pollen-induced allergic rhinitis in passively and actively sensitized guinea pigs.

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.

Airway Resistance↗
PubMed1989

The effect of cetirizine on early allergic response.

A double blind, placebo-controlled, cross-over study was performed to determine the effect of cetirizine, an H1 antihistamine, on the immediate nasal allergic response. Ten persons underwent nasal challenge with antigen after premedication with 20 mg of cetirizine or placebo QD for 2 days. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, leukotriene C4, albumin, and TAME-esterase activity in recovered nasal lavages. The results showed a significant reduction in sneezing and in the amounts of recovered albumin, TAME-esterase activity, and leukotriene C4 but no reduction in the amounts of recovered histamine and prostaglandin D2. These results suggest that cetirizine does not inhibit mast cell activation but inhibits the consequences of the released histamine on H1 receptors: sneezing and increased vascular permeability. The results further suggest that mast cell release of histamine is the direct result of antigen stimulation, as opposed to reflex activation, and that other cells in addition to mast cells generate leukotrienes during the early allergic response.

Albumins↗
PubMedDate not supplied

A comparison of aqueous suspensions of budesonide nasal spray (128 micrograms and 256 micrograms once daily) and fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of adult patients with seasonal allergic rhinitis.

The efficacy of aqueous suspensions of budesonide nasal spray and fluticasone propionate nasal spray, in the treatment of seasonal allergic rhinitis, was compared in a large, placebo-controlled, two-center study. A 1-week baseline period was followed by a 4- to 6-week treatment period during which 635 adult patients, aged 18-72 years, were randomized to receive either placebo, budesonide 128 micrograms, or 256 micrograms once daily, or fluticasone propionate, 200 micrograms once daily. Nasal and eye symptoms, overall treatment efficacy and safety assessments were made during the study period. Combined, as well as individual, nasal symptoms were significantly improved in all three active treatment groups compared with placebo therapy. Treatment with 256 micrograms/day of budesonide was found to be significantly more effective in reducing the sneezing score compared with 200 micrograms/day of fluticasone propionate. Analysis of symptom scores on days when the pollen count was greater than 10 grains/m3 revealed 256 micrograms/day of budesonide therapy to be significantly more effective in reducing combined symptom scores as well as the individual scores for sneezing and runny nose, compared with 200 micrograms/day fluticasone propionate. The higher dose of budesonide (256 micrograms/day) was also more effective than the lower dose (128 micrograms/day) in reducing sneezing scores and statistical significance was almost reached for the reduction in combined symptom and runny nose scores. Substantial or total control of symptoms was achieved by 31.4%, 85.3%, 88.4%, and 81.9% of patients receiving placebo, 128 micrograms/day of budesonide, 256 micrograms/day of budesonide, and 200 micrograms/day of fluticasone propionate, respectively. The incidence of adverse events was low in all treatment groups. In conclusion, both budesonide and fluticasone propionate treatments were effective and well-tolerated in the treatment of seasonal allergic rhinitis. However, 256 micrograms/day of budesonide tended to be more effective than 200 micrograms/day of fluticasone propionate and 128 micrograms/day of budesonide, especially when patients were exposed to a higher pollen load.

Administration, Intranasal↗
PubMedDate not supplied

Nasopharyngeal diseases in cats: a retrospective study of 53 cases (1991-1998).

The records of 53 cats with nasopharyngeal disease were examined. Of the cats with nasopharyngeal disease, 49% had lymphosarcoma and 28% had polyps. Clinical signs in these cats were compared to 24 cats with nasal disease alone. Cats with only nasal disease more commonly had historical nasal discharge and sneeze, whereas cats with nasopharyngeal disease more often had stertorous respiration, phonation change, and typically reported less nasal discharge or sneeze. It is important to include nasopharyngeal disease in the differential diagnosis for cats with nasal discharge, sneeze, stertor, or phonation change.

Animals↗
PubMedDate not supplied

A randomized controlled trial of cetirizine plus pseudoephedrine versus loratadine plus pseudoephedrine for perennial allergic rhinitis.

The purpose of this study was to compare the safety and efficacy of cetirizine plus pseudoephedrine (C+P) with loratadine plus pseudoephedrine (L+P) in the treatment of perennial allergic rhinitis. This was a double blind, randomized, parallel trial with an active control. Subjects aged 12 to 70 years with perennial allergic rhinitis for at least 2 years were enrolled and randomized to receive either of the active study medications plus a placebo resembling the other, twice daily for 4 weeks. Nasal total symptom scale (NTSS) including sneezing, rhinorrhea, nasal itching and nasal stuffiness is evaluated by subjects daily and at baseline, 2 weeks, and 4 weeks by the investigator as efficacy measurement. A total of 51 eligible patients were enrolled and 45 patients completed the treatment course. Both groups had significant reductions in NTSS after 4 weeks of treatment as assessed by the subjects, but there was no significant difference between the two groups (mean +/- SD) reduction of 4.25 +/- 2.45 with C+P vs. 3.52 +/- 2.41 with L+P, p = 0.215. As assessed by the investigator, sneezing was significantly better at 2 weeks (-1.13 vs. -0.52, p = 0.028) and nasal congestion at 4 weeks (-1.71 vs. -1.19, p = 0.031) in subjects treated with C+P compared to those treated with L+P. There were 37 treatment-related adverse events (5 in 4 subjects in the C+P group and 32 in 16 subjects in the L+P group). It was concluded that both cetirizine plus pseudoephedrine and loratadine plus pseudoephedrine are efficacious for perennial allergic rhinitis in Taiwanese subjects. Relief of sneezing and nasal congestion may be marginally better with the cetirizine preparation, which also seemed to be slightly better tolerated, although the incidence of side effects did not differ significantly.

Adolescent↗
PubMed1991

[Nasal provocation test with histamine: rhinomanometry study of normal subjects].

Nasal reactivity to histamine was evaluated in 40 normal subjects. The application of a chloride histamine solution (1 mg) registered in 90% of the subjects the appearance of sneezing with the number of sneezes ranging between one and fourteen (5.7 +/- 3.76) and an average increase in the total resistence in the inspiration phase of 93.1% (+/- 63.2) and in the expiration phase of 98.1% (+/- 60.5) with a range between 37.7% and 24.1%. The authors conclude that sneezing and above all nasal congestion evaluated rhinomanometrically represent two important parameters in the evaluation of nasal reaction; an increase greater than or equal to 200% of the total nasal resistance can surely be considered an index of nasal hyperreactivity.

Adolescent↗
PubMed2003

Antihistamines for the common cold.

BACKGROUND: Although antihistamines are prescribed in large quantities for the common cold, there is little evidence to whether these drugs are effective. OBJECTIVES: To assess in patients with a common cold the effects of antihistamines in alleviating nasal symptoms, or in shortening of illness duration. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections Group Specialized Register and EMBASE up to December 2002; Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to February 2003. We also followed up references in identified papers. We appealed for further articles at a major international conference on Acute Respiratory Infections (1997). We corresponded with experts and got in touch with pharmaceutical companies. SELECTION CRITERIA: Randomised, placebo-controlled trials on treatment of common cold with antihistamines, used either singly or in combination, in adults or children. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and authors were contacted for further data. Trials were subdivided into monotherapy and combination therapy. Data on general recovery, nasal obstruction, rhinorrhea, sneezing, and side-effects were extracted and summarized in a systematic review. MAIN RESULTS: We included thirty two papers describing 35 comparisons; 22 trials studied monotherapy, 13 trials a combination of antihistamines with other medication. A total of 8930 people suffering from the common cold were included. There were large differences in study designs, participants, interventions, and outcomes. There was no evidence of any clinically significant effect - in children or in adults - on general recovery of antihistamines in monotherapy. First generation - but not non-sedating - antihistamines have a small effect on rhinorrhea and sneezing. In trials with first generation antihistamines the incidence of side effects (especially sedation) is significantly higher with active treatment. Two trials, studying a combination of antihistamines with decongestives in small children, both failed to show any effect. Of the eleven trials on older children and adults, the majority show an effect on general recovery and on nasal symptom severity. REVIEWER'S CONCLUSIONS: Antihistamines in monotherapy - in children as well as in adults - do not alleviate to a clinical extend nasal congestion, rhinorrhoea and sneezing, or subjective improvement of the common cold. First generation antihistamines also cause more side-effects than placebo, in particular they increase sedation in cold sufferers. Combinations of antihistamines with decongestives are not effective in small children. In older children and adults most trials show a beneficial effect on general recovery as well as on nasal symptoms. It is however not clear whether these effects are clinically significant.

Common Cold↗