The effect of locally applied ipratropium aerosol on the nasal methacholine challenge in patients with allergic and non-allergic rhinitis

The effect of local pretreatment with ipratropium versus placebo aerosol on nasal methacholine challenge was studied in a double-blind, crossover trial. Fourteen allergic and ten non-allergic patients suffering from rhinitis participated in this study. It can be concluded that intranasal administration of ipratropium has a suppressive effect on hypersecretion and sneezing, but has no influence on nasal airway resistance.     

Significance of H1 and H2 receptors in the human nose: rationale for topical use of combined antihistamine preparations

The aim of this experiment was to study the importance of histamine H1 and H2 receptors in the human nose. We therefore provoked 25 healthy human subjects with histamine after local pretreatment with the H1 receptor antagonist, chlorpheniramine maleate, the H2 receptor antagonist, ranitidine hydrochloride, and a combination of these two antihistamines. The histamine-induced increase in nasal airway resistance was 52% inhibited by combined use of the two antihistamine sprays (p less than 0.05), 22% by chlorpheniramine alone (p less than 0.05), and 29% by ranitidine. The two sprays together were significantly better than the H1 antagonists alone (p less than 0.05). These results suggest an equal importance of H1 and H2 receptors in nasal blood vessels, and an additive effect of H1 and H2 antihistamines. Although chlorpheniramine effectively blocked tickling and the reflex-mediated symptoms, sneezing and hypersecretion, ranitidine had no effect, which suggests an H1 and not an H2 effect on sensory nerve endings in the airway epithelium.     

Effect of Topically Applied Atropine, Methysergide and Chlorpheniramine on Nasal Challenge with Serotonin

Serotonin challenge in the nose produces sneezing and rhinorrhoea. To study the mode of action of serotonin in the nose, 14 normal persons, in a double-blind, randomized study, were provoked with serotonin in three concentrations. Fifteen minutes before challenge, they were pretreated in the nose with either a cholinoceptor antagonist (atropine), a serotonin antagonist (methysergide), an H1-histamine antagonist (chlorpheniramine) or isotonic saline. The number of sneezes was noted, and the amount of secretions measured. Serotonin induced dose-related increase in sneezing and hypersecretion (P less than 0.02). Atropine pretreatment reduced the amount of secretion (P less than 0.05 and P less than 0.1), but had no effect on sneezing. Methysergide and chlorpheniramine had no effect on the serotonin-induced nasal symptoms. Unilateral challenge with serotonin induced secretions from both sides, suggesting that serotonin-induced nasal symptoms are partly reflex-mediated.     

Study of the effects of paf-acether on human nasal airways

In 6 normal subjects and 6 patients with allergic rhinitis, nasal response to insufflation of paf-acether (paf, platelet-activating factor), lyso-paf and histamine was evaluated. Nasal challenge with paf, at doses of 300 and 600 nM, induced nasal obstruction, associated with an increase in nasal airway resistances, measured by anterior passive rhinomanometry. Maximum increase in nasal airway resistance was observed at 30 min after challenge (mean percent change + 481 with 600 nM paf; P less than 0.05). Other symptoms induced by paf insufflation were rhinorrhea (6 out of 12 subjects), itching (8 out of 12), sneezing (4 out of 12) and a burning sensation (6 out of 12). No differences were observed between normal and rhinitic subjects, concerning nasal sensitivity to paf. Neither nasal symptoms nor changes in nasal airway resistance were observed after nasal challenge with lyso-paf (300 and 600 nM); by contrast, histamine (100 nM) induced sneezing, nasal obstruction, itching and rhinorrhea in all the studied subjects, associated with an increase in nasal airway resistance (maximum 5 min after challenge; percent change + 358; P less than 0.02). Nasal effects of paf were not mediated by histamine, since no increase in histamine levels was observed in nasal washings following paf insufflation. We conclude that paf may have pathogenetic relevance in allergic rhinitis.     

Nasal histamine release following hyperosmolar and allergen challenge

Allergic rhinitis is characterised by symptoms of sneezing, itching of the nose with watery secretions, and nasal obstruction. We have previously shown that patients can have the diagnosis of allergic rhinitis confirmed by nasal provocation tests and assessment of nasal inspiratory peak flow (NIPF) after specific allergen or hyperosmolar challenge. We now show that histamine is released into the nasal lavage fluid in response to such challenges. Saline lavage alone results in detectable histamine levels in the order of 5 ng/ml, but in the presence of allergen (HDM) there is a significant increase in histamine release in atopics but not in control subjects. With hyperosmolar challenge, atopics showed a biphasic response in that histamine release was increased with 1.8% and 3.6% saline but returned to baseline with 5.4% and 7.2% saline, then showing a further increase with 9.0% saline. This raises the possibility of two populations of responsive mast cells. Hyperosmolar challenge leads to symptoms of nasal itch and sneezing as well as histamine release in atopics but not in controls. This suggests that hyperosmolar challenge can be used as a simple diagnostic test for allergic rhinitis and may provide a model for nasal hyper-reactivity.     

Use of nasal peak flow to assess nasal patency

Nasal patency is usually assessed in the laboratory by measuring nasal airflow conductance ( Gnaw ); peak inspiratory and/or expiratory flow measurements via the nose (PIFna, PEFna) have been proposed as simple alternatives suitable for home monitoring of rhinitis. We have compared the scale of changes in PIFna and PEFna (measured with a pneumotachograph) with changes in Gnaw (measured by the forced-oscillation technique) when nasal patency was increased by a topical α-adrenergic agonist, xylometazoline (five control subjects, seven with seasonal rhinitis, studied when asymptomatic) or decreased by topical histamine (eight control subjects). In further experiments, we altered intrapulmonary airway calibre by having subjects inhale histamine or salbutamol aerosols and examined effects on the configuration of nasal flow-volume curves (six subjects with rhinitis and mild asthma). After topical xylometazoline, there was a mean 283% increase in Gnaw 80% increase in PEFna, and 63% increase in PIFna. After topical histamine, there was a mean 72% decrease in Gnaw, 38% decrease in PEFna, and 39% decrease in PIFna. Inducing intrapulmonary airway obstruction sometimes obscured changes in nasal patency by removing the effects of added nasal resistance on expiration and preventing development of flow limitation in the nose on inspiration. Thus, after topical drug treatment to the nose, changes in Gnaw were considerably larger than in PEFna or PIFna, which were proportionately similar. Because PIFna is usually restricted by nasal flow limitation, it is probably superior to PEFna for assessing nasal patency. When effort is submaximal, intrapulmonary dynamic resistance is increased, or nasal dynamic resistance is low, PEFna and PIFna can give a misleading impression of nasal patency. These errors can be avoided by comparisons with mouth PEF and/or PIF, suggesting that nasal and mouth peak flow should both be measured during home monitoring.     

Histamine nasal provocation test

This study is a methodological approach to histamine nasal provocation. The test uses active anterior rhinomanometry and a histamine titration method, challenging both nasal cavities with a metered dose pump. It has been confirmed that the histamine nasal provocation test can differentiate between controls and non-allergic rhinitis patients. This study shows, moreover, that the method is more sensitive in assessing response to histamine provocation when a 25% increase of post-saline nasal airway resistance (PD25) is considered than a PD50 or PD100 criterion. The histamine response, was found to be independent of the baseline nasal airway resistance value. Pronounced unilateral responsiveness was frequently noticed. Both nasal cavities should be challenged and the most reactive side considered.     

The effect of local hyperthermia on allergen-induced nasal congestion and mediator release

Background: Local hyperthermia reduces mast cell degranulation, the severity of acute lung injury, and exercise-induced asthma and decreases symptoms of rhinitis. We have investigated the effect of local hyperthermia on mast cell degranulation and symptom generation in allergic rhinitis to assess its effect and mechanism of action within the nose.Methods: In a randomized, double-blind, placebo-controlled, crossover study, 10 subjects with rhinitis were treated for 30 minutes with local hyperthermia or placebo, which was followed 30 minutes later by nasal allergen challenge. During the first two visits nasal lavages were performed to assess vascular leakage and mediator release. During the last two visits nasal airway resistance, the number of sneezes, and mucus secretion were monitored.Results: Local hyperthermia significantly reduced both nasal airway resistance (p < 0.05) and vascular leakage (p < 0.02) but had no significant effect on the number of sneezes, on mucus secretion, or on tryptase release.Conclusion: Local hyperthermia reduces allergen provoked nasal blockage and vascular leakage but has no effect on sneezing, rhinorrhea, or tryptase release. Nasal blockage occurs predominantly via newly formed lipid mediators and kinins, whereas sneezing and rhinorrhea occur predominantly via preformed mediators. We propose that local hyperthermia inhibits newly formed mediator production or release or reduces the sensitivity of the vasculature to inflammatory mediators in general. Further investigation into the mechanisms and potential uses of local hyperthermia is warranted.     

Involvement of thromboxane A2 and peptide leukotrienes in early and late phase nasal blockage in a guinea pig model of allergic rhinitis

OBJECTIVE AND DESIGN: We investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness to histamine using a guinea pig model of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs were challenged once every week for 13 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 4th, 6th and 13th challenge. METHODS: Sneezing frequency and the change in specific airway resistance (sRaw) were measured at these challenges. Two days after the 13th challenge, nasal responsiveness to histamine was evaluated by measuring sRaw after intranasal instillation of increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th challenge. RESULTS: Only terfenadine (10 mg/kg) significantly inhibited sneezing at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late phase elevation of sRaw (biphasic nasal blockage), although the degree of inhibition on the early phase response varied with the challenge time. In contrast, the development of nasal hyperresponsiveness to histamine was inhibited by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and histamine in NCLF were observed after the challenge in sensitized animals. CONCLUSIONS: These results suggest that TXA2 and p-LTs, but not histamine, play important roles in both the early and the late phase nasal blockage in this model of allergic rhinitis.     

Activity of substance P on human skin and nasal airways

Nasal challenge and intradermal injection with substance P (SP) were performed in five normal subjects and in five patients suffering from allergic rhinitis. No clinical symptoms, local histamine release, or modifications of nasal airway resistance were observed when SP was insufflated in the nose. Conversely, intradermal injection with SP caused a wheal and flare reaction in all the studied subjects. The different response to SP is likely to be due to the heterogeneity of human skin and nasal mucosa mast cells as far as sensitivity to histamine-releasing agents is concerned. Our findings indicate that SP has no relevant effect on human nasal mucosa, even if a synergetic action of SP with other allergic mediators cannot be excluded. The role of SP in the pathogenesis of allergic diseases in humans remains to be defined and deserves further study.     

Exudative hyperresponsiveness of the airway microcirculation in seasonal allergic rhinitis

Background Mucosal exudation of plasma is a non-injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The educative response is a specific end-organ function of the mucosal microcirculation that may be altered in airway diseases. Objective This study examines the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability-increasing challenges in sustained allergic inflammation. Methods Fourteen patients with birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch-pollen season. Nasal symptoms (itching, sneezing. blockage, and discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a‘nasal pool’ -device. The unilateral nasal cavity was filled for consecutive 10 minute periods with saline and two concentrations of histamine (80μg/ mL and 400μg/mL). The lavage fluid levels of different-sized plasma proteins (albumin-66 000 D. fibrinogen-340000 D, and α₂-macroglobulin-725000D) were determined. Results The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and α₂-macroglobulin (r =0.98; P< 0.001). The exudative response to histamine was concentration-dependent (P<0.05) and, furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05. tibrinogen: P<0.05. α₂-macroglobulin: P<0.01). Conclusion We conclude that histamine produced concentration-dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the mierovascular endothelium may explain this phenomenon now remains unknown. We suggest that a mierovascular exudative hyperresponsiveness may characterize allergic airway disease.     

Histamine and methacholine do not increase nasal reactivity

Abstract. Allergen provocation in the nose increases the non-specific nasal reactivity. The aim of this trial was to determine whether this'priming effect' can be caused by histamine or methacholine, which is the most important biochemical mediator of allergic rhinitis, and an analogue to the important neurotransmittor, acetylcholine, respectively. Intranasal provocation tests with the two substances were carried out on thirteen normal subjects, and repeated 1 hr and 1 day later. The response, measured as the number of sneezes, the amount of blown secretion and the increase in nasal airway resistance, did not change with consecutive provocations. It was concluded that neither histamine nor methacholine were responsible for the allergen-induced'priming' of the nasal mucous membrane.     

Nasal symptoms in persons with normal nose]

BACKGROUND: Nasal symptoms such as sneezing, stuffy nose and runny nose occur in allergic and nonallergic rhinitis. Normal nose also sometimes has these symptoms. It is necessary to define what is the symptom of normal nose in order to make a proper diagnosis of rhinitis, grading of severity of nasal symptom in rhinitis and criteria of normalization after the treatment of rhinitis. METHODS: 235 persons who had no perceptive nasal symptom and history of nasal disease at present and past, and cold at present, were sampled from the registered list of a health care organization, and examined their nasal symptom by mailing a self-administered questionnaire of nasal symptom. In addition, 54 patients, who visited 4 otolarngology clinics due to diseases other than rhinitis and were diagnosed as normal nose, were examined, using the same questionnaire. RESULTS: Response rate from persons mailed was 49.8%. Nasal symptom was infrequent in patients at clinic more than persons sampled from the list. Nasal symptom in 117 responders with normal nose had none or occasional and momentary stuffy nose. Sneezing and/or nose blow was less than 5 times a day, and itchy nose and postnasal drip were 30% and 25% respectively. These symptoms, if appeared, were less than 4 days per week. CONCLUSION: Grading "minus", normal, is zero in sneezing and runny nose and none in stuffy nose in the grading system of nasal symptom used commonly in Japan. These should be changed to none or occasional, momentary, easily tolerable in stuffy nose, less than once a day or grading "plus one" (1-5 times per day) occasionally in sneezing and nose blow. Normalization after treatment could be defined according to this change.     

Attenuation of histamine-induced airway effects by intranasal application of levocetirizine in mice

Abstract

The present study was performed to investigate the histamine-induced airway effect of levocetirizine, an active enantiomer of cetirizine, by intranasal application using ddY mice. Nasal rubbing and sneezing after histamine application into the nasal cavity were used as an index of histamine-induced airway effect in mice. Intranasal application of levocetirizine inhibited both nasal rubbing and sneezing concentration-dependently, and the ED₅₀ values were 0.62 (0.51–0.77) and 0.70 (0.51–1.02) %/site for nasal rubbing and sneezing, respectively. ED₅₀ values of cetirizine were 1.24 (1.02–1.59) and 1.35 (1.02–2.08) %/site for nasal rubbing and sneezing, respectively. Levocetirizine also inhibited nasal rubbing and sneezing when administered orally. These results clearly indicate that levocetirizine was about two times more potent than cetirizine by intranasal application, similar to the findings of the former’s affinity for human histamine H₁ receptors. In addition, the present findings raise the expectation of the development of levocetirizine nasal drops.     

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.     

Effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice

We studied the effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice. A single administration of propolis caused no significant effect on both antigen-induced nasal rubbing and sneezing at a dose of 1000?mg/kg, but a significant inhibition was observed after repeated administration for 2 weeks at this dose. Propolis caused no significant inhibitory effect on the production of total IgE level after repeated administration of 1000?mg/kg. The drug also caused no significant inhibition of histamine-induced nasal rubbing and sneezing at a dose of 1000?mg/kg. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by antigen and compound 48/80 at a concentration of more than 10 μg/ml. These results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.     

The role of leukotriene D4 in allergic rhinitis

We investigated the clinical significance of leukotriene D4 (LTD4) in nasal symptoms of allergy and compared this with antigen and histamine. Nasal provocations were carried out in patients with allergic rhinitis using serially increasing doses of LTD4, histamine, or antigen. The nasal responses induced were evaluated by counting the number of sneezes, the quantity of nasal secretion, and of nasal airway resistance. When the effects of topical provoking agents were compared at the threshold concentration, LTD4 produced no sneezing--unlike antigen and histamine--increased nasal secretion to a lesser degree than antigen and histamine (P less than .001), and increased nasal airway resistance similar to histamine but less than antigen (P less than .1) and longer than histamine, and similar to antigen in duration. LTD4 was approximately 5,000 times stronger than histamine in threshold concentration for nasal response. In conclusion, LTD4 plays an important role in nasal allergy presumably through long lasting and strong nasal blockage effects.     

Rhinitis in adults

Rhinitis is a very common disorder caused by inflammation or irritation of nasal mucosa. Dominant symptoms are nasal obstruction; however, in some patients, runny nose, excessive sneezing or nasal itch may be the most bothersome symptoms. The most common causes of nasal inflammation are viral infections and allergic response to airborne allergens. Response to irritants may cause similar symptoms, although signs of inflammation may not always be present. Viral rhinitis is lasting up to 10 days and it is part of the common cold syndrome. In short-lived rhinitis, lasting for 7 to 10 days, sometimes it is not easy to differentiate between the potential causes of the disorder, if general symptoms of infection like fever and malaise are not present. In long-living rhinitis, it is important to differentiate between infectious, allergic, non-allergic non-infectious rhinitis, and chronic rhinosinusitis. Itch and ocular symptoms are more common in allergic rhinitis, while other symptoms like nasal obstruction, rhinorrhea and sneezing may affect patients with allergic and non-allergic rhinitis. Patients with allergic rhinitis often have symptoms after exposure to irritants, temperature and humidity changes, like patients with non-allergic rhinitis, and such exposure may sometimes cause more severe symptoms than exposure to allergens. Sensitivity to a non-specific trigger is usually called non-specific nasal hyperreactivity. Allergic rhinitis occurs due to immunoglobulin E (IgE) interaction with allergen in contact with nasal mucosa in a sensitized patient. Sensitization to certain airborne allergen, like pollens, dust, molds, animal dander, etc. usually occurs in families with allergy background, which is helpful in making diagnosis in patients who have rhinitis in a certain period of the year, or aggravation of nasal symptoms occurs in the environment typical of certain allergen. The diagnosis is clinically confirmed by proving sensitivity to certain allergen on skin prick test, and by proving specific antibody IgE in patient serum. Allergic rhinitis is categorized according to sensitivity to allergens that occur seasonally, like pollens, or to allergens that are present all year round, like house dust mite, molds and animal dander, into seasonal and perennial allergic rhinitis. Allergy to pollens causes the same mechanism of inflammation in response to allergens, which is the result of allergen binding to specific IgE antibody; however, patients with pollen allergy usually complain more of sneezing and runny nose, whereas patients with allergy to perennial allergens more often complain of obstruction, with the episodes of sneezing and runny nose occurring only when exposed to higher concentrations of allergens (house cleaning, around pets). Treatment includes avoidance of allergens, medical treatment and immunotherapy (allergy vaccines, tablets with allergens). Avoidance of allergens means reduction of environmental allergen load to the respiratory system including workplace, which is not easy to accomplish. Medical treatment is usually necessary to control symptoms, and it includes antihistamines, nasal or in tablets, and nasal glucocorticoids (steroids). Antihistamines should be second generation, which do not cause sedation, and such treatment shows more efficacy on runny nose, sneezing and nasal itch than on nasal stuffiness. Nasal steroids are more potent in improving nasal patency than antihistamines, and are at least as potent in the control of all other nasal and ocular symptoms. Nasal patency may be improved by nasal or oral decongestants, but such treatment should be reduced to as short period as possible, since after several days of using nasal decongestants rebound congestion may occur and patients will need nasal decongestants to improve nasal airways even when allergens are not around anymore.     

Nasal histamine challenges in symptomatic allergic rhinitis

Twenty subjects (seven with perennial allergic rhinitis, seven with symptomatic seasonal allergic rhinitis, and six normal control subjects) underwent assessment of nasal sensitivity to histamine. Nasal resistance was measured by posterior rhinometry under control conditions and after log incremental doses of histamine solution pipetted into the nose (0.5 to 5000 micrograms). Allergic subjects exhibited a twofold rise of nasal resistance with doses of 0.5, 5, or 50 micrograms of histamine, whereas the nasal resistance in normal subjects remained unchanged until 500 or 5000 micrograms of histamine had been administered. Nasal reactivity to histamine was not correlated with symptoms on the day of testing but was correlated with the number of positive wheals to skin prick testing. It was concluded that nasal resistance is more sensitive to histamine in subjects with allergic rhinitis than in normal control subjects and that this difference may be used as the basis of a diagnostic test.     

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.