Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and asthma

Although H1 antihistamine compounds (H1) are highly effective in the treatment of allergic rhinitis (AR), their role in the treatment of asthma is still controversial. Because a strong association between AR and bronchial hyperresponsiveness (BHR) has been reported, this study was designed to assess the effect of a new H1 anti histamine, cetirizine (C), on nonspecific BHR in patients with AR. Twelve patients were included in a double-blind, crossover, placebo-controlled trial. All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge. After a washout period of 1 week to ensure the stability of the BHR, the patients received, by crossover randomization, C 10 mg daily or placebo (P) for 2 weeks. After each treatment period, BHR and nasal blocking index (NBI) were measured 1 and 6 h after nasal challenge. Bronchial responsiveness was expressed as methacholine PD20, the provocation dose of methacholine causing a 20% decrease in FEV1. Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 (median) measured before challenge showed no difference after cetirizine or after placebo (1.36 mg). Results 1 h after allergen did not show significant differences between C (methacholine PD20=0.522 mg) and placebo (methacholine PD20=0.455 mg). By contrast, 6 h after challenge, methacholine PD20 was 0.918 mg for C and 0.483 mg for P (P=0.042). Similarly, NBI showed no change between C and P 1 h after challenge, whereas the difference was significant 6 h after challenge (P=0.011 ). These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR. They suggest that C may be useful in patients with asthma associated with AR.     

Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo

Background Interleukin-8 (IL-8) hus been shown to be a chemotactic factor for netitrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which arc released trotn C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. Methods IL-8 at a dose of 5μg/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness. Result The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. Conclusion We conclude that repeated intranasal administratioti of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.     

Bronchial hyperresponsiveness in young children with allergic rhinitis and its risk factors

BACKGROUND: Subjects with allergic rhinitis but no clinical evidence of asthma have greater bronchial hyperresponsiveness (BHR), and several factors have been implicated as its determinants. However, studies in young children are lacking. The aims of this study were to evaluate the prevalence of BHR in young children with allergic rhinitis and to investigate its risk factors. METHODS: Methacholine bronchial challenges were performed in 4- to 6-year-old nonasthmatic children with allergic rhinitis (n = 83) and in healthy nonatopic controls (n = 32), using a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Subjects were considered to have BHR when they had end-point concentrations of methacholine 相似文献   

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.     

Effect of allergen immunotherapy on nasal responses in guinea-pigs with allergic rhinitis

Methods We have investigated the effects of allergen immunotherapy on the nasal responses in the guinea-pigs with allergic rhinitis. Thirty-three male Hartley guinea-pigs with allergic rhinitis were divided into three groups; those receiving intradermal injection of saline (Group 1) or 0.1% ovalbumin (Group 2) 6 days after the last intranasal sensitization, and those injected with 0.1% ovalbumin intradermally once daily for 6 consecutive days from the next day after the last intranasal sensitization (Group 3). Results The dye leakage and histamine content into the nasal lavage significantly decreased at 30min after antigen challenge in Group 3, compared with Group 1 or 2. We also observed the change of mast cell numbers in superficial nasal mucosa, lamina propria and injected dorsal skin. The number of mast cells in superficial nasal mucosa significantly decreased in Group 3 compared with Group 1 or 2, but not those in nasal lamina propria or dorsal skin. Conclusions These results suggest that the improvements of nasal responses such as dye leakage and histamine content may be caused by the decrease of mast cell numbers in the superficial mucosal layer after the specific immunotherapy. which may be developing tolerance and one of the mechanisms underlying the beneficial effect of immunotherapy.     

Evaluation of cytokine mRNA in induced sputum from patients with allergic rhinitis: relationship to airway hyperresponsiveness

Background:  Although airway hyperresponsiveness (AHR) is a characteristic feature of asthma, it is also frequently present in allergic rhinitis (AR). However, the pathogenesis of AHR is unclear and the roles of cytokines in the airway have not been well established in AR. We sought to compare cytokine mRNA levels in the sputum of AR patients with or without AHR and those of asthma patients, and to evaluate whether differences in cytokine levels are associated with the development of an abnormal airway response and the absence of respiratory symptoms in AR patients with AHR.
Methods:  Airway cells were obtained by sputum induction from 18 AR patients with AHR, 58 AR patients without AHR, and 27 asthma patients. Airway cell cytokine levels, interleukin (IL) -4, IL-5, IL-13, vascular endothelial growth factor (VEGF), and interferon-γ (IFN-γ), were studied at the mRNA level by RT-PCR.
Results:  Vascular endothelial growth factor and IL-5 mRNA levels were significantly higher in AR patients with AHR than in AR patients without AHR, but these were lower than those of asthmatic patients. Eosinophils were significantly higher in AR patients with AHR and in asthmatic patients than in AR patients without AHR. Interleukin-4, IL-13, and IFN-γ levels were not elevated in AR patients with or without AHR vs asthma patients.
Conclusions:  These findings suggest that VEGF and IL-5 can be important determinants of the development of AHR in AR patients and that lower levels of other cytokines may be associated with the absence of asthmatic symptoms in AR patients with AHR.     

Fexofenadine reduces nasal congestion in perennial allergic rhinitis

BACKGROUND: Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late-phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy. METHODS: This study was a parallel, double-blind, randomized, three-arm (1:1:1), placebo-controlled study. Thirty-one subjects with PAR were enrolled and received double-blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days. RESULTS: The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect. CONCLUSIONS: This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.     

Reduction of soluble ICAM-1 levels in nasal secretion by H1-blockers in seasonal allergic rhinitis

ICAM-1, a transmembrane glycoprotein promoting adhesion in immunologic and inflammatory reactions, was found to be increased on nasal epithelial cells of patients with allergic rhinitis. Loratadinae, an H₁-Mocker, was found to reduce in vitro the expression of ICAM-1 on nasal epithelial cells. A double-blind, parallel-group study was carried out during the pollen season to compare the effect of two H₁-blockers, cetiraizine (10 mg OD) and loratadine (10 mg OD), on the release of soluble ICAM-1 in nasal secretions. A group of untreated patients was used as a control group. sICAM-1 was measured by enzyme immunoassay before and after 2 weeks of treatment. Symptoms were significantly decreased in the actively treated groups. sICAM-1 levels were unchanged in the control group but were significantly reduced in the two treated groups ( P <0.015, Wilcoxon's W test). This study shows that two H₁-blockers, loratadine and cetirizinae, have a similar effect on sICAM-1 released in nasal secretions during the pollen season.     

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.     

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up

BACKGROUND: A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. METHODS: Twenty-eight children (6-15 years) with AR were studied. At enrollment (T(0)), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)(1) fall (PD(20)FEV(1)) and as dose-response slope (D(RS)). Subjects were reassessed after 7 years (T(1)) using the same criteria. RESULTS: At T(0), 13 children (46%), showing a PD(20)FEV(1) <1526 microg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered. CONCLUSION: Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.     

Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation

BACKGROUND: The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. METHODS: Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. RESULTS: Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. CONCLUSION: Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.     

Local nasal immunotherapy in allergic rhinitis to Parietaria

Preseasonal local nasal immunotherapy (LNIT) by means of an extract in macronized powder form has been studied in allergic rhinitis to parielaria . Twenty-four Parietari-sensitive patients have been studied for 18 weeks in a double-blind controlled trial. Subjects were selected on the basis of a positive skin test, RAST and intranasal challenge to Parietaria antigen. Three eight-patient groups were randomly planned: the first group was given native Parietaria product, the second modified Parietaria product, and the third placebo. During the pollen season no difference was observed in mean weekly symptom score between the three groups, while the mean weekly medication score was significantly lower in the treated groups than the control group. Only the treated groups showed a significant increase in specific nasal threshold to Parietaria after treatment. Adverse reactions to LNIT, limited to the upper respiratory tract, occurred rarely and did not interfere with the dose schedule. This study indicates that L nit in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety.     

Mometasone furoate monohydrate nasal spray for the treatment of nasal congestion in allergic rhinitis

Allergic rhinitis (AR) affects an estimated 20–40 million Americans annually. It is a multifaceted condition comprising a range of symptoms, including nasal congestion, arguably the most bothersome symptom. Of the various types of medications available for the treatment of AR, intranasal corticosteroids are considered the most effective. Mometasone furoate nasal spray is an intranasal corticosteroid with anti-inflammatory properties. It is indicated for the treatment of the nasal symptoms of seasonal AR and perennial AR in adults and children, for the prophylaxis of nasal symptoms of seasonal AR and for the treatment of nasal polyps. Numerous clinical trials have demonstrated that mometasone furoate nasal spray effectively relieves nasal congestion in adults and children with AR, while providing excellent safety and tolerability.     

氮卓斯丁喷鼻剂治疗过敏性鼻炎的临床疗效观察

氮卓斯丁是一种新型抗组胺药,为考察氮卓斯丁喷鼻剂治疗过敏性鼻炎的疗效和安全性,进行了本项临床试验。采用多中心、随机、双盲、平行对照的方法,对照药为左卡巴斯丁喷鼻剂,受试者为中重度过敏性鼻炎患者,季节性过敏性鼻炎和常年性过敏性鼻炎分别连续给药14d和28d。共有136例完成了临床试验,氮卓斯丁组67例,左卡巴斯丁组69例。氮卓斯丁组总有效率82．1％,其中显效40．3％,左卡巴斯丁组则分别为76．8％和20．3％。两组均未发现严重不良反应。氮卓斯丁组与左卡巴斯丁组的不良反应发生率分别为22．1％和31．5％。氮卓斯丁组主要副作用为鼻干8．8％、口苦8．8％,左卡巴斯丁组主要副作用为鼻干16．4％、口干9．6％。氮卓斯丁喷鼻剂治疗过敏性鼻炎有较好的疗效和安全性。