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

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

Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study

BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared. RESULTS: Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. CONCLUSION: A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.     

Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis

Background: Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis. Objective: The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray. Methods: This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment). Results: Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P = .03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P = .009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P = .01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient. Conclusions: Once daily budesonide aqueous nasal spray, 256 μg, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 μg, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone. (J Allergy Clin Immunol 1998;102:902-8.)     

The effect of nedocromil sodium on nasal provocation with allergen

We have investigated the effect of nedocromil sodium in preventing the symptoms of rhinitis occurring immediately after allergen provocation in 10 patients with allergic rhinitis. The study had a double-blind, placebo-controlled, crossover design. Nedocromil sodium (1% w/v) and placebo were administered intranasally from identical metered-dose inhalers 20 minutes before allergen provocation. Three variables were measured: nasal airway resistance, the production of secretion, and the number of sneezes. Nedocromil sodium was significantly more effective than placebo in preventing nasal obstruction (p less than 0.01), rhinorrhea (p less than 0.01), and sneezing (p less than 0.05), suggesting that this drug may be useful in the treatment of allergic rhinitis.     

Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy

Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.     

Comparison of the effects of fluticasone propionate, aqueous nasal spray and levocabastine on inflammatory cells in nasal lavage and clinical activity during the pollen season in seasonal rhinitics

BACKGROUND: Treatment options for allergic rhinitis include antihistamines, decongestants, anticholinergics, cromolyn sodium and corticosteroids. As the nose is a small organ, comprising less than 1% of total body mass and surface area, it seems logical to confine treatment of rhinitis to the diseased organ. OBJECTIVE: To evaluate the effects of therapy with intranasal fluticasone propionate (FP), both on subjective symptoms and pathophysiological mechanisms, in rhinitis patients during pollen season when the patients were symptomatic. METHODS: We used a double-blind, placebo (PLA)-controlled, randomized, double dummy, parallel group study of the effect of 6 weeks treatment. The double-blind comparison was made between the following three treatments: FP aqueous nasal spray, 200 microg taken once daily, levocabastine (LEV) nasal spray, 200 microg taken twice daily and PLA nasal spray. Clinical evaluation and the levels of cells and mediators in nasal washing were performed before and after treatments. Twenty-four patients (11 men and 13 women, aged 17-50 years, mean age 30.1 +/- 8.5) with strictly seasonal allergic rhinitis to Parietaria entered the study. Clinical evaluation and the levels of inflammatory cells (eosinophils and activated eosinophils, i.e. EG2+) and their mediators (tryptase, eosinophil cationic protein, eosinophil protein X and neutrophil myeloperoxidase) in nasal-lavage were performed before and after treatments. RESULTS: Treatment with FP significantly increased, with respect to placebo, the percentage of days without sneezing (P < 0. 001), nasal blockage (P < 0.001), rhinorrhea (P < 0.001), nasal itching (P < 0.001). Furthermore, treatment with FP showed additional benefits with respect to LEV. The percentage of days without nasal blockage was significantly higher in the FP group that in the placebo group (P = 0.018). The same applied to rhinorrhea (P = 0.009). The percentages of days without sneezing and itching were instead not significantly different between the two groups. As expected, no significant differences were observed in baseline medians of the rhinitis symptom scores as well as in mean values of all mediators and eosinophils in nasal lavages of the various groups under study. After treatment the mean of subjective symptoms as well as all values in nasal lavage level fell significantly only in the FP group, whereas no significant changes were observed either in LEV or PLA groups. Accordingly, significant differences were observed at the end of the treatments between the values of fluticasone group vs LEV and PLA group values. Significant correlations between these values and symptom scores were found, according with literature data suggesting a pathogenetic role for these mediators and eosinophils in rhinitis. CONCLUSION: FP (200 microg once daily) affords a significant degree of improvement in rhinitis control during pollen season, as measured by subjective and objective parameters, compared with LEV (200 microg twice daily) and PLA. The therapeutic benefits of intranasal FP are reflected in, and may be caused by, the decrease in nasal inflammatory cells.     

Intranasal Steroids in the Treatment of Allergy-Induced Rhinorrhea

While nasal congestion has been identified as one of the most bothersome and prevalent symptoms of allergic rhinitis, it is underappreciated that many patients find rhinorrhea also to be bothersome. Rhinorrhea as a symptom of allergic rhinitis virtually never occurs alone; about 97% of patients with allergic rhinitis suffer from at least two symptoms, a finding that underscores the advantage of treating a broad range of symptoms with a single medication. Along with sneezing and nasal obstruction, rhinorrhea is a classic acute symptom of allergic rhinitis; it appears as a late-phase symptom as well. In this review, the characterization and epidemiology of rhinorrhea, the pathophysiology of rhinorrhea in allergic rhinitis, the roles played by mediators in early- and late-phase rhinorrhea, the prevalence and impact of this symptom, and the efficacy and safety of available treatment options are all discussed in context of relevant literature. A review of the clinical studies assessing the efficacy of intranasal corticosteroids (INS) for rhinorrhea is presented. Many clinical studies and several meta-analyses conclusively demonstrate that, in addition to being safe and well-tolerated, INS are more effective than other agents (including oral and intranasal antihistamines) across the spectrum of AR symptoms, including rhinorrhea and nasal congestion.     

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVE: To compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children. METHODS: Thirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy. RESULTS: Both treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP. CONCLUSIONS: Ipratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.     

Tryptase in nasal fluid is a useful marker of allergic rhinitis

Tryptase is a mast cell-specific marker of degranulation. To investigate the possible diagnostic value of tryptase in allergic rhinitis, we measured the levels in both serum and native nasal fluid with a sandwich RIA-assay (Pharmacia). Twenty-three allergic patients and five patients with chronic ethmoidal sinusitis were included. Eighteen of the 23 allergic patients were tested within the pollen season or had perennial rhinitis; the remainder were tested at least 1 month out of the pollen season. None of the patients had detectable serum tryptase (>0.1 ng/ml). Also patients with chronic ethmoidal sinusitis showed no tryptase in nasal fluid. One of seven allergic patients tested out of season had slightly increased nasal tryptase of 1.8 ng/ml. In patients with active nasal allergy, the tryptase in nasal fluid ranged from 6.4 ng/ml to 640 ng/ml with a mean of 101 ng/ml and SD 173. These results show a clear distinction between active and non-active nasal allergy and other non-mast-cell-related nasal disease. Further, nasal tryptase release by natural allergen exposure is even higher than that observed in allergen challenge tests.     

An approach to the understanding of the nasal early-phase reaction induced by nasal allergen challenge

Quantitative determinations of the inflammatory mediators in nasal secretions were performed and correlated with the objective nasal symptoms within 1 h after nasal allergen challenge (NAC). Twenty-six patients with seasonal allergic rhinitis were enrolled outside the pollen season. All measurements were performed before (as a baseline control) and at 1, 5, 10, 30, and 60 min after NAC. This study aimed to clarify the pathogenic mechanism of the early-phase reaction (EPR) by monitoring the evolution of early-phase mediators in nasal secretions and the presence of nasal symptoms during this period. The results showed that, after NAC, the maximal mediator concentration was already reached after 1 min for histamine (124 ng/g), 5 min for tryptase (56 μU/g), and 5-10 min for leukotriene C₄ (40 ng/g). Itching and sneezing started as early as 20-30 s, and they were predominant symptoms within 5 min. Rhinorrhea and nasal obstruction started a few minutes after NAC and lasted until more than 1 h after NAC. There was no significant correlation between any single mediator and nasal symptoms during the sampling period. In conclusion, this study demonstrated that during the EPR the presence of nasal symptoms involves a complex mechanism, reflecting the interaction between the mediators released by inflammatory cells, and the receptors on different target organs. When evaluating symptoms during the EPR, one must consider not only the severity of these symptoms but also the time period within which these symptoms occur. For the symptoms of nasal obstruction and rhinorrhea, the early-phase reaction often lasted more than 1 h.     

Local allergic rhinitis: concept, pathophysiology, and management

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.     

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.     

Glucocorticoid-induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 μg per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa.     

Comparison of a nasal glucocorticoid,antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis

BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis. OBJECTIVE: We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid. METHODS: In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops and a limited amount of loratadine were allowed as rescue medication for severe symptoms. Patients recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens were obtained from patients for evaluation of local eosinophilic inflammation. RESULTS: During the peak season, both FPANS and combined montelukast-loratadine were significantly more effective than placebo and montelukast alone for daytime symptom prevention. For nighttime symptoms, FPANS was significantly more effective compared with all other treatments, whereas combined montelukast-loratadine and montelukast alone did not provide significant symptom prevention compared with placebo. The pollen-induced increase in the numbers of epithelial eosinophils was significantly lower for FPANS-treated patients compared with that seen in all other treatment groups. CONCLUSION: In patients with seasonal allergic rhinitis, intranasal glucocorticoids are more effective than an antileukotriene drug or combined antileukotriene-antihistamine for the reduction of pollen-induced nasal eosinophilic inflammation and for control of nasal symptoms.     

Fluticasone propionate aqueous nasal spray compared with oral loratadine in patients with seasonal allergic rhinitis*

The effectiveness and safety of fluticasone propionate aqueous nasal spray (200 μg once daily for 4 weeks) were compared with those of loratadine (10 mg once daily for 4 weeks) in 114 adults and adolescents with seasonal allergic rhinitis in this multicenter, double-blind, double-dummy, randomized, parallel-group study. Patients recorded their nasal symptoms (nighttime and daytime obstruction, sneezing, itching, rhinorrhea, and overall discomfort) using a 4-point scale (0=no symptoms, 3=very frequent symptoms) in daily diaries. Clinicians assessed patients' nasal symptoms (nighttime and daytime obstruction, sneezing, itching, and rhinorrhea) using a 4-point scale at every scheduled visit. Clinicians and patients assessed the overall effectiveness of treatment at the end of the study. Fluticasone propionate improved clinician-rated total nasal symptom scores (defined as the sum of five nasal symptoms) more than loratadine at the 2-week and 4-week assessments (P≥0.008). Clinicians gave fluticasone propionate better global ratings than loratadine (P=0.04). After 4 weeks of treatment, between-group differences in clinician-rated individual nasal symptoms favored fluticasone propionate (P<0.05), with the exception of nasal itching (P=0.11). These findings were confirmed by between-group differences in the percentages of symptom-free days calculated from patient-recorded daily diary-card data. Both treatments were well tolerated. The incidence of adverse events between groups was similar. Fluticasone propionate aqueous nasal spray 200 μg administered once daily in the morning was more effective than loratadine 10 mg administered once daily for the treatment of seasonal allergic rhinitis.     

Nasal cytology in allergic processes and other syndromes caused by hyperreactivity

The spontaneous nasal secretions from about 128 patients with the symptomatic triad of rhinorrhea, sneezing, and nasal obstruction were studied. The cytological examination consisted of a morphological evaluation and a semiquantitative evaluation. Noncellular and nonliving presences in the smears have been considered, including mucus, Charcot-Layden crystals, and pollen grains, as well as fungi and bacilli. We found a net increase in eosinophils, goblet cells, and cellular debris in secretions of atopic patients. Pollen grains and vegetative fragments were present in the nasal smears of pollinosis. The presence of fungi was observed in five cases of allergic rhinopathy. The exfoliative cytology represents a valuable means for the differential diagnosis of rhinitis. In particular, the presence of noncellular elements has value regarding rhinocytology.     

The rationale for use of topical corticosteroids in allergic rhinitis

The rationale for using topical corticosteroids in the treatment of allergic rhinitis is that high drug concentrations can be achieved at receptor sites in the nasal mucosa, with minimal risk of systemic adverse effects. Topical corticosteroids have been demonstrated to reduce the number of Langerhans' cells (or their markers) in the nasal mucosa, and this is thought to attenuate antigen presentation. T lymphocytes have been identified as being significant in orchestrating the immune-inflammatory response, particularly the TH₂ cells, which represent an important target for topical corticosteroids. TH₂ cell-evoked mast cells and basophils are the sole producers of histamine, a mediator of major importance for rhinitis symptoms. Several studies have shown that the increased number of mast cells and basophils in the epithelium following antigen challenge/exposure, are markedly reduced by topical corticosteroids. Furthermore, the number of eosinophils, an important morphological marker of allergic rhinitis, can be profoundly reduced by treatment with topical corticosteroids. The rationale for topical treatment is strengthened by evidence of inhibition of cytokine release from surface epithelial cells, resulting in reduced recruitment and activation of mast cells, basophils, and eosinophils, which may be attributed to the high drug concentration achieved in epithelial cells. Ongoing inflammation in the mucous membrane is indicated by entry of plasma into the nasal lumen which subsides with the anti-inflammatory efficacy of topical corticosteroids. In contrast to anlihistamine therapy, which has little effect on nasal blockage, pretreatment with topical corticosteroids results in almost complete attenuation of late-phase symptoms including nasal blockage, and moderate efficacy in early phase symptoms. Clearly, the spectrum of anti-inflammatory activity afforded by topical corticosteroid therapy is of clinical significance in reducing the three major symptoms of allergic rhinitis — sneezing, watery rhinorrhoea and nasal blockage.     

Nonallergic rhinitis with eosinophilia syndrome a precursor of the triad: nasal polyposis, intrinsic asthma, and intolerance to aspirin

Fifty-two cases of perennial rhinitis were studied, leading to the diagnosis of seven cases of nonallergic rhinitis with eosinophilia syndrome (NARES) a frequency of 13.5%. Symptoms of nasal hyperreactivity involving sneezing, rhinorrhea, nasal obstruction and pruritus were more severe than in other types of rhinitis. The frequency of hyposmia was very specific to NARES. Nasal endoscopy and sinus CT revealed an evolution towards nasal polyposis in four patients. The nasal challenge to house dust mites showed the absence of any increase in local eosinophilia. Bronchial hyperreactivity to carbachol occurred in one case. There was no case of intolerance to aspirin. There was particular adrenergic hyperreactivity among the seven patients, evidenced by study of the reactivity of the cardiovascular alpha and beta receptors. The authors emphasize the features that are shared by NARES and by the triad, which suggest that NARES is the early phase of the triad. They advance the pathogenic hypothesis of an autonomic nervous system dysregulation with a predominating adrenergic hyperreactivity. Inflammatory effects of local release of neurotransmitters induce a switch from a neurogenic to a self-sustaining inflammation. Tissue eosinophilia is regulated by chemical attractants and activating substances of various origins and plays a major part in the chronic inflammatory state.     

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.