EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Production of Rice Seed-Based Allergy Vaccines.

Recombinant hypoallergenic derivative is the next generation of tolerogen replacing the natural allergen extract to increase safety and efficacy. Japanese cedar pollinosis is the predominant seasonal allergy disease in Japan. A rice seed-based oral vaccine containing the recombinant hypoallergens derived from these allergens was developed. Efficacy of this rice-based allergy vaccine was evaluated by oral administration in animal models.

Intranasal exposure to monoclonal antibody Fab fragments to Japanese cedar pollen Cry j1 suppresses Japanese cedar pollen-induced allergic rhinitis.

BACKGROUND AND PURPOSE: Fab fragments (Fabs) of antibodies have the ability to bind to specific allergens but lack the Fc portion that exerts effector functions via binding to receptors including FcεR1 on mast cells. In the present study, we investigated whether intranasal administration of the effector function-lacking Fabs of a monoclonal antibody IgG1 (mAb, P1-8) to the major allergen Cry j1 of Japanese cedar pollen (JCP) suppressed JCP-induced allergic rhinitis in mice. EXPERIMENTAL APPROACH: Balb/c mice sensitized with JCP on days 0 and 14 were challenged intranasally with the pollen on days 28, 29, 30 and 35. Fabs prepared by the digestion of P1-8 with papain were also administered intranasally 15 min before each JCP challenge. KEY RESULTS: Intranasal administration of P1-8 Fabs was followed by marked suppression of sneezing and nasal rubbing in mice with JCP-induced allergic rhinitis. The suppression of these allergic symptoms by P1-8 Fabs was associated with decreases in mast cells and eosinophils and decreased hyperplasia of goblet cells in the nasal mucosa. CONCLUSIONS AND IMPLICATIONS: These results demonstrated that intranasal exposure to P1-8 Fabs was effective in suppressing JCP-induced allergic rhinitis in mice, suggesting that allergen-specific mAb Fabs might be used as a tool to regulate allergic pollinosis.

Effect of Asian sand dust on Japanese cedar pollinosis.

OBJECTIVE: Asian sand dust (ASD), originating in the deserts of Mongolia and China, spreads over large areas and is associated with adverse effects on human health in East Asia, including asthma, heart disease, and some allergic diseases. However, the effect of ASD on patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), the most common form of allergic rhinitis, remains unclear. The aim of this study was to investigate the effect of ASD on SAR-JCP patients. METHODS: A total of 41 patients with SAR-JCP recorded nasal and ocular allergic symptom scores in a diary. We assessed the influence of ASD events on patients with SAR-JCP during the JCP season and before and after the JCP season. RESULTS: ASD events did not influence nasal and ocular allergy symptoms during the JCP season. Scores for sneezing and runny nose were significantly increased by ASD events in the pre-JCP season. Ocular symptom scores were significantly increased by ASD events in the post-JCP season. CONCLUSION: Our results suggest that ASD may exacerbate allergy symptoms even before mass scattering of JCP, which usually does not cause allergic symptoms in patients with SAR-JCP. ASD also induced conjunctivitis symptoms after the JCP season. However, we did not observe any adverse effects of ASD on allergic symptoms during the JCP season.

A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion.

BACKGROUND: H1-receptor inverse agonists are used effectively for treating several symptoms of allergic rhinitis, including nasal itching, rhinorrhea, and sneezing, although most agents are not very effective in treating nasal congestion. OBJECTIVE: This study evaluated the relative efficacy of a novel selective H3-receptor antagonist, JNJ-39220675, in preventing nasal congestion induced by exposing participants with ragweed allergy to ragweed allergen in an environmental exposure chamber model. METHODS: In this single-dose, patient-blind, double-dummy, placebo- and active-controlled, phase IIa cross-over study, 53 participants were randomized to JNJ-39220675 plus placebo, placebo plus pseudoephedrine, or only placebo. The primary efficacy assessment was change in nasal patency assessed by measuring the minimal cross-sectional area of the nasal cavity by using acoustic rhinometry. Secondary assessment included total nasal symptom scores (TNSSs) over the 8-hour environmental exposure chamber exposure period. RESULTS: Smaller decreases in minimal cross-sectional area were observed after JNJ-39220675 (least square mean difference, -0.126; P = .06) and pseudoephedrine (least square mean difference, -0.195; P = .004) treatment compared with placebo. The means for the baseline-adjusted area under the curve of TNSSs were significantly smaller for JNJ-39220675 (P = .0003) and pseudoephedrine (P = .04) versus placebo. JNJ-39220675 was significantly effective in treating all 4 individual symptoms (P ≤ .05 for all scores) compared with placebo, whereas pseudoephedrine only showed a trend for improvement in individual symptom scores of the TNSS. Insomnia was the most frequent adverse event (17.3%) associated with JNJ-39220675 treatment. CONCLUSION: Prophylactic treatment with the H3-antagonist JNJ-39220675 relieved allergen-induced nasal congestion by using standard nasal symptom scoring; however, in contrast to pseudoephedrine, it only showed a trend for increasing nasal patency by using objective measures.

Therapeutic effects of ß1, 4 mannobiose in a Balb/c mouse model of intranasally-induced pollen allergy.

BACKGROUND: Nutritional prebiotic supplementation represents an attractive approach for interventions of allergy. In this study, the potential therapeutic effect of ß-1, 4 mannobiose (MNB) in a murine model of cedar pollinosis was investigated. METHODS: Groups of Balb/c mice were intranasally sensitized to Japanese cedar pollen extract, and subsequently administered with low or high dose MNB. Both intraperitoneal and intranasal challenges were performed to monitor for clinical signs. Frequency of sneezing was recorded. Serum, spleen and Peyer's patches were collected for various biomarker analyses. Anti-allergic activity of MNB using RBL-2H3 cells was also evaluated. RESULTS: Significant decrease in sneezing frequency, histamine, interleukin (IL)-4 and IL-17A and increase in TGF-ß and IL-10 concentration were exhibited by the MNB-treated mice. However, Cry j1 and Cry j 2-specific IgE activity remained unaltered. The high dose MNB treatment increased total IgA activity and IL-10, TGF-ß and FoxP3 and decreased IL-4, IL-17A, and RORγT mRNA expression. Inhibition of activation of RBL-2H3 cells was observed via decrease in histamine, intracellular Ca2+ concentration, and FcεRI mRNA expression. CONCLUSIONS: We demonstrated the immunomodulatory effects of MNB and conclude that MNB is a potential therapeutic molecular nutritional supplement candidate for treatment of pollen allergy.

When sneezing indicates the cell type.

BACKGROUND: Nasal hyperreactivity is the symptomatic expression of vasomotor rhinitis. This study describes a typical nasal reaction, represented by a "volley of sneezes" found in some patients during nasal endoscopy, and to assess the possible correlation between hyperreactivity and a particular clinical and cytological condition. METHODS: We studied 671 rhinological subjects, 344 male, mean age 35.7 ± 13.76 standard deviation (SD) years. All were submitted to medical histories and clinical and instrumental investigations (skin prick test, nasal endoscopy, and nasal cytology). While performing endoscopy, particular attention was paid to the possible signs of nasal hyperreactivity, in particular "volley of sneezes" both during and immediately after the diagnostic procedure. RESULTS: Out of 671 endoscopies performed, 130 (17.1%) patients presented signs of hyperreactivity during and/or immediately after nasal endoscopy. The ratio of positive vasomotor reaction was 10.6% in the nasal polyposis (NP) group, 19% in the allergic rhinitis (AR) group, 70.6% (p < 0.01) in nonallergic rhinitis with mast cells (NARMA), 76% (p < 0.01) in nonallergic rhinitis with eosinophils and mast cells (NARESMA), and 83% (p < 0.01) in nonallergic rhinitis with eosinophils (NARES). In the AR subjects hyperreactivity was more frequent during the pollen season, compared to the period of absence of pollen (87.5% vs 12%). CONCLUSION: The onset of hyperreactivity (sneezing) can be considered an important "sign" in nasal symptomatology, whose sensitivity and specificity for nonallergic "cellular" rhinitis are 79% and 93%, respectively.

Effect of 5-aminosalicylate on allergic rhinitis model in mice.

Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in allergic rhinitis. It has been reported that 5-aminosalicylate (5-ASA) has an affinity for PPARgamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL)-4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA-specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis.

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

BACKGROUND: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. METHOD: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. RESULTS: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. CONCLUSIONS: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

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 microg/ml. These results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.

Clinical efficacy of halophilic lactic acid bacterium Tetragenococcus halophilus Th221 from soy sauce moromi for perennial allergic rhinitis.

BACKGROUND: Recently, some common foods in daily life, especially lactic acid bacteria, have been found to have anti-allergic effects. We previously isolated a halophilic lactic acid bacterium, Tetragenococcus halophilus Th221, from soy sauce moromi, a mixture of koji and salt solution, and showed that it possesses an immunomodulatory activity that promotes T helper type 1 immunity. METHODS: To evaluate the anti-allergic effects of Th221, we performed a randomized, double-blind, placebo-controlled study in 45 subjects with perennial allergic rhinitis (PAR) treated by oral administration of Th221 (high dose, 60 mg/day, 15 subjects; low dose, 20.4 mg/day, 15 subjects) or a placebo (15 subjects) for 8 weeks. RESULTS: There were no significant differences among the groups that ingested Th221 and the placebo group regarding the disease severities, total nasal symptom scores and total nasal sign scores examined by physicians. However, the disease severity examined by physicians significantly improved in the high-dose group at the end of the trial compared with the beginning (p < 0.05). The total score for nasal symptoms of subjects who received a high dose of Th221 also showed a significant improvement at the end of the trial compared with the beginning (p < 0.01). According to the subjects' diaries, significant improvements in sneezing and rhinorrhea were observed during some periods in the high-dose group. The change in serum total immunoglobulin E improved significantly at the end of the trial compared with the beginning in this group (p < 0.05). The safety of Th221 treatment was confirmed by laboratory tests and inspection of the general condition of each subject. CONCLUSIONS: Th221 can be expected to safely improve the symptoms of PAR.

Absence of nasal blockage in a Japanese cedar pollen-induced allergic rhinitis model mouse.

BACKGROUND: Japanese cedar pollen-induced allergic rhinitis in a guinea pig model clearly induced not only sneezing but also biphasic nasal blockage. To date, there have only been a few reports on models of murine allergic rhinitis which clearly show nasal blockage. Therefore, in order to try and develop such a model, we administered multiple dosages of intranasal pollen or purified antigen protein Cry j 1. METHODS: B10.S mice were sensitized by intranasal instillations of either pollen extract or Cry j 1 twice a day for 7 days, which was adsorbed on Al(OH)(3). Subsequently, once a week, the mice were given multiple intranasal instillation challenges of either the pollen suspension or Cry j 1 and the frequency of sneezing was observed after respective challenges were made. Specific airway resistance (sRaw) was measured as an indicator for nasal blockage. Cry j 1-specific IgE levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The serum Cry j 1-specific IgE level showed clear elevation only in the group sensitized by Cry j 1 + Al(OH)(3) and then challenged by Cry j 1. No elevations were seen in the groups sensitized by pollen extract + Al(OH)(3) followed by a pollen suspension challenge. There was an immediate increase in sneezing after challenges in all of the sensitized-challenged groups. Nevertheless, no increases in sRaw in any of the groups were detected at any of the time points during the 8 hours following the challenges. CONCLUSIONS: Cry j 1 may be more effective than crude antigens for efficient sensitization/challenge in mice. No increase in sRaw occurred, even in mice that possessed high amounts of Cry j 1-specific IgE and that exhibited sneezing.

Effects of endogenous glucocorticoids on allergic inflammation and T(H)1 /T(H)2 balance in airway allergic disease.

BACKGROUND: Glucocorticoids play an important role in modulating allergic inflammation and immune response. However, little is known about the role of endogenous glucocorticoids in airway allergic disease. OBJECTIVE: To investigate the effects of endogenous glucocorticoids on regulating allergic inflammation and T(H)1/T(H)2 balance in an airway allergic murine model. METHODS: An ovalbumin-sensitized murine model was established by intraperitoneal injection sensitization and intranasal challenge with ovalbumin. Glucocorticoid release was inhibited by administration of metyrapone, and the peripheral glucocorticoid receptors were blocked by administration of RU486. The numbers of eosinophils in the lung, peripheral blood, and bone marrow were quantified. The changes in T(H)2/T(H)1 cells were investigated by flow cytometry, and their cytokines were tested by enzyme-linked immunosorbent assay, including interleukin 4, interleukin 5, and interferon gamma, in the supernatant of the spleen cell culture. RESULTS: Inhibition of endogenous glucocorticoids caused more sneezing and further increased eosinophil counts in the peripheral blood and bone marrow of the sensitized mice. However, by inhibition of endogenous glucocorticoids, the interferon gamma levels were upregulated, the interleukin 4 and 5 levels were down-regulated, and the ratio of T(H)2/T(H)1 cells decreased significantly, indicating a shift to a T(H)1-predominant immune response in sensitized mice. CONCLUSIONS: Our findings suggest that endogenous glucocorticoids play an important role in abating allergic inflammatory reaction and modulating the T(H)1/T(H)2 balance in an airway allergic murine model. Inhibition of endogenous glucocorticoids resulted in a shift to T(H)1 predominance, but that did not attenuate the severity of the allergic inflammatory reaction.

A clinical study of Japanese cedar (Cryptomeria japonica) pollen-induced asthma.

BACKGROUND: Grass and birch pollens are known to induce asthma. However there are few reports about other pollen-induced asthma. Japanese cedar is the most common allergen in rhinitis in Japan but is controversial on whether it can provoke asthma. METHODS: To clarify Japanese cedar pollen-induced asthma, we studied adult patients who were sensitized only to the Japanese cedar (CAP-RAST > = 2) and had symptoms of asthma during the cedar season. We defined cedar asthma as a patient who satisfied the 2 criteria mentioned above. RESULTS: We found 6 adult asthma patients who fulfilled the two criteria. Five patients suffered from cedar pollinosis in addition to asthma, and 1 patient had no pollinosis. The cedar pollinosis preceded asthma in 3 cases and occurred at almost the same time in the other 2 cases. Pulmonary function was normal in these cases (FEV 1%, mean +/- SD, 76.5 +/- 10%), with a high threshold value in the non-specific airway hypersensitivity test (Ach-PC20, 2,696 to 20,000 microg/ml, 9294 +/- 2) and low total IgE (101 +/- 86 IU/ml). In the allergen provocation test, 3 subjects showed both an immediate and late asthmatic reaction. CONCLUSIONS: We concluded that Japanese cedar pollen could provoke not only pollinosis but also asthma in adults.

Validation of guinea pig model of allergic rhinitis by oral and topical drugs.

Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in the studies of rhinitis. Systemic sensitization and challenge with ovalbumin-induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers, positive skin reactions and nasal lavage IL-4 concentration. Histopathology of nasal mucosa showed infiltration of eosinophils and other inflammatory cells consistent with the symptoms. Topical sensitization of ovalbumin yielded inconsistent symptoms of rhinitis. In systemic sensitization model, repeated challenge of ovalbumin caused similar response for at least 3 consecutive challenges. The symptoms were affected by relative humidity in the air and dosing volume of topical drugs. Sneezing and lacrimation were reduced by acute oral administration of the H1 receptor antagonists and steroids or the prophylactic oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist montelukast or acute topical antihistamines, mast cell stabilizer sodium cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical steroid. Nose rubbing was reduced significantly by some oral and topical antihistamines. Oral steroids offered excellent protection against all symptoms. Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2 weeks had no effect on sneezing or rubbing. However, it caused complete inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant oxymetazoline caused reduction in congestion. These results suggest that differential responsiveness to symptoms of rhinitis by a new agent can be very well profiled in the model in congruence with the mediation pathways and mechanism of action of drugs. The model provides complete symptomatic characterization of rhinitis and is a good tool for its study.

Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid in subjects with birch pollen allergy.

Animal studies suggest that conjugated linoleic acid (CLA) may modulate the immune response, while studies in healthy human subjects have shown little effect and results are controversial. However, the effects of CLA may be more prominent in situations of immune imbalance, such as allergy. We studied the effects of the natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological parameters in subjects with birch pollen allergy. In a randomised, placebo-controlled study, forty subjects (20-46 years) with diagnosed birch pollen allergy received 2 g CLA/d in capsules, which contained 65.3 % cis-9, trans-11-CLA and 8.5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before the birch pollen season and continued throughout the season. Allergy symptoms and use of medication were recorded daily. Lymphocyte subsets, cytokine production, immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid peroxidation were assessed before and after supplementation. The CLA group reported a better overall feeling of wellbeing (P < 0.05) and less sneezing (P < 0.05) during the pollen season. CLA supplementation decreased the in vitro production of TNF-alpha (P < 0.01), interferon-gamma (P < 0.05) and IL-5 (P < 0.05). Total plasma IgE and birch-specific IgE concentrations did not differ between groups, whereas plasma IgA (P < 0.05), granulocyte macrophage colony-stimulating factor (P < 0.05) and eosinophil-derived neurotoxin (P < 0.05) concentrations were lower after CLA supplementation. Urinary excretion of 8-iso-PGF2alpha, a major F2-isoprostane (P < 0.01), and 15-keto-dihydro-PGF2alpha, a primary PGF2alpha metabolite (P < 0.05), increased in the CLA group. The results suggest that cis-9, trans-11-CLA has modest anti-inflammatory effects in allergic subjects.

Differential responses to various classes of drugs in a model of allergic rhinitis in guinea pigs.

Different drugs from various pharmacological classes were compared for their ability to protect against the nasal effects of acute allergen challenge in a guinea pig model. In the model, sneezing and nose rubbing were recorded after an initial allergen challenge in guinea pigs previously sensitized to egg albumin. Four days later the same guinea pigs were re-challenged a second time when anesthetised. In these anaesthetized animals, nasal airway pressure, pulmonary inflation pressure and cellular infiltration into nasal lavage fluid were measured. The drug tested were autacoid antagonists (mepyramine--3mg/kg, cetirizine--3mg/kg and montelukast--10mg/kg), L-NAME (10 or 20mg/kg), heparin (20mg/kg) and dexamethasone (20mg/kg) given either intraperitoneally or intravenously; all were given shortly before challenge. Sneezing induced by allergen challenge was statistically significantly reduced by mepyramine, cetirizine and dexamethasone whereas only cetirizine reduced nose rubbing. Changes in nasal airway pressure due to allergen exposure were reduced by cetirizine, montelukast, L-NAME, and heparin, but not by mepyramine, nor dexamethasone. In the presence of L-NAME, nasal airway pressure actually changed in the opposite direction. Cellular infiltration, as assessed by cytometry in nasal lavage fluid 60min after acute allergen challenge, was reduced by montelukast and heparin but not by antihistamines, L-NAME nor dexamethasone. This pattern of effects of the drugs, given by doses and routes previously described in the literature as being effective was not completely consistent with expected responses. The lack of effect of dexamethasone probably reflects the fact that it was given acutely whereas in the clinic chronic administration is used. The two antihistamines were not identical in their actions, presumably reflecting the fact that cetirizine has therapeutic actions not entirely confined to blockade of H1 receptors. Montelukast has not been reported to have major effects on sneezing and itching in the clinic but reduces nasal obstruction (lower nasal airway pressure or nasal patency). Montelukast's effects on cellular infiltration indicate the possible involvement of leukotrienes. Heparin has actions on inflammatory cell infiltration. This could explain its profile of reducing both cellular infiltration, and increased nasal airway pressure.