Efficacy and onset of action of fluticasone propionate aqueous nasal spray on nasal symptoms, eosinophil count, and mediator release after nasal allergen challenge in patients with seasonal allergic rhinitis

We studied the effect and onset of action of fluticasone propionate aqueous nasal spray (FPANS) on mediator release and eosinophil accumulation in nasal secretions and on nasal symptoms of patients with seasonal allergic rhinitis after nasal allergen challenge (NAC). At the end of the pollen season, 28 patients were randomized in a double-blind and crossover design to receive 7 days' treatment with FPANS (200 μg, once daily) and matching placebo. NACs were performed before and at 6 h and 1. 2. 3. and 7 days during treatment with FPANS or placebo. Nasal secretions were collected for a quantitative determination of mediators and eosinophil count before and 5 min after each challenge. Nasal symptoms were assessed by scales grading the severity of symptoms at the same time. Results showed that for mediator concentrations there was a significant decrease of leukotriene C4 (P<0.001) at 7 days after the first administration of FPANS as compared to placebo. Two days after FPANS. both eosinophil counts and eosinophil cationic protein (ECP) concentrations were lower than those of placebo (eosinophils; f=0.032; ECP; F=0.038). The onset became even more important at day 7 (eosinophils; P=0.001; ECP; P=0.009) during the FPANS treatment period. For the subjective nasal symptoms, a significant reduction of symptom scores for nasal obstruction occurred also at day 3 (F=0.017) and for sneezing at day 7 (f=0.003). There was not yet any significant improvement of the objective nasal airway resistance after the different NACs during the study period. In conclusion, this study demonstrated that topical fluticasone propionate is effective in the treatment of mucosal inflammation induced by NAC. For optimal control of nasal symptoms induced by repeated maximal allergen challenges, a treatment period of more than 1 week is required.     

中药雾化对慢性单纯性鼻炎鼻腔粘膜微循环血流量的影响

目的:探讨中药雾化吸入对慢性单纯性鼻炎患者鼻腔粘膜微循环血流量的影响。方法:60例患者采用复方丹参、鱼腥草注射液超声雾化治疗3疗程。分别于治疗前后采用吸入性氢气清除法测定鼻粘膜微循环血流量的变化。结果:慢性单纯性鼻炎鼻粘膜微循环血流量较健康对照组明显减低,经雾化治疗后得到明显改善,其差异有极显著性意义(P<0.01)。结论:慢性单纯性鼻炎患者经中药雾化治疗后鼻粘膜微循环血流量明显增加,临床效果较好。     

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs

Background: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. Methods: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. Results: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 μg/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 μg/kg to 10 μg/kg intravenously) (p > 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. Conclusion: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo. (J ALLERGY CLIN IMMUNOL 1995;96:910-6.)     

Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps

BACKGROUND: Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder. OBJECTIVE: We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype. METHODS: We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks. RESULTS: Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps. CONCLUSION: These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.     

Prevalence of asthma, allergic rhinoconjunctivitis and allergic sensitization in Mongolia

BACKGROUND: Studies in countries, such as Mongolia, which are in transition from farming to industrial society permit evaluation of the impact of environmental change on atopic diseases. METHODS: In the screening study, questionnaire data were obtained from 9453 subjects aged 10-60 years. In the clinical study, a subsample of 869 subjects (participation rate 50.0%) was examined. A questionnaire-based interview, clinical examination, skin prick tests, spirometry and bronchodilation test or methacholine challenge test were used to define the clinical diagnoses. The prevalences of atopic diseases were evaluated at the population level using two-phase data and sampling weights. RESULTS: The prevalences of asthma, allergic rhinoconjunctivitis and allergic sensitization with 95% confidence intervals were 1.1% (0.3-2.0%), 9.3% (4.0-14.6%) and 13.6% (7.4-19.9%) in Mongolian villages, 2.4% (1.4-3.5%), 12.9% (8.2-17.7%) and 25.3% (17.1-33.6%) in rural towns and 2.1% (1.3-3.0%), 18.4% (13.3-23.4%) and 31.0% (24.5-37.5%) in Ulaanbaatar city, respectively. The prevalence of allergic rhinoconjunctivitis (P = 0.02) and allergic sensitization (P = 0.003) increased significantly with increasing urbanization. CONCLUSIONS: The prevalences of atopic diseases were low in rural Mongolia and increased with increasing urbanization suggesting that rural living environment protects against atopy.     

The ARIA/EAACI criteria for antihistamines: an assessment of the efficacy, safety and pharmacology of desloratadine

Background:  The definition of allergic rhinitis and the classification of its severity and treatment have advanced in recent years following the publication of the Allergic Rhinitis and its Impact of Asthma (ARIA) document. The ARIA and the European Academy of Allergology and Clinical Immunology (ARIA/EAACI) have published a set of recommendations that outline the pharmacological and clinical criteria to be met by medications commonly used in the treatment of allergic rhinitis.
Methods:  An international group of experts met to assess the profile of the antihistamine, desloratadine, under the ARIA/EAACI criteria. Data on desloratadine were collected from peer-reviewed clinical studies and review articles, which were corroborated and augmented by comprehensive public access documents from the European Medicines Evaluation Agency (EMEA).
Results and conclusion:  Based on this systematic review, it was concluded that the efficacy, safety and pharmacology of desloratadine broadly meet the ARIA/EAACI criteria for antihistamines.     

Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection

BACKGROUND: Although the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti-IgE) may be unsafe in subjects at risk of helminth infection. OBJECTIVE: We conducted an exploratory study to investigate the safety of omalizumab (anti-IgE) in subjects with allergic asthma and/or perennial allergic rhinitis at high risk of intestinal helminth infection. The primary safety outcome was risk of infections with intestinal helminths during anti-IgE therapy. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 137 subjects (12-30 years) at high risk of geohelminth infection. All subjects received pre-study anthelmintic treatment, followed by 52 weeks' treatment with omalizumab or placebo. RESULTS: Of the omalizumab subjects 50% (34/68) experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects [odds ratio (OR) 1.47, 95% confidence interval (CI) 0.74-2.95, one-sided P=0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94-5.15); one-sided P=0.035], providing some evidence for a potential increased incidence of geohelminth infection in subjects receiving omalizumab. Omalizumab therapy was well tolerated, and did not appear to be associated with increased morbidity attributable to intestinal helminths as assessed by clinical and laboratory adverse events, maximal helminth infection intensities and additional anthelmintic requirements. Time to first infection (OR 1.30, 95% CI 0.79-2.15, one-sided P=0.15) was similar between treatment groups. Infection severity and response to anthelmintics appeared to be unaffected by omalizumab therapy. CONCLUSIONS: In this exploratory study of allergic subjects at high risk of helminth infections, omalizumab therapy appeared to be safe and well tolerated, but may be associated with a modest increase in the incidence of geohelminth infection.     

A multicentre study of loratadine, clemastine and placebo in patients with perennial allergic rhinitis

This multicentre, double-blind, randomized parallel-group study compared 3 weeks' treatment with either loratadine (Clarityn) 10 mg once daily, or clemastine (Tavegyl) 1 mg twice daily, and placebo in outpatients with active perennial allergic rhinitis. 155 patients were evaluated for efficacy and safety. Grading of four nasal and three non-nasal symptoms, rhinoscopy signs, and therapeutic response was performed on treatment days 6, 13, and 20. Patients recorded daily symptoms and possible adverse experiences in a diary, also indicating when symptoms of active rhinitis were relieved. Loratadine and clemastine were statistically significantly superior to placebo throughout the study (P less than 0.05), based on assessment of patients' nasal and eye symptoms, patients' diary scores, rhinoscopy signs of symptoms, and onset of relief. The loratadine group showed a statistically significantly (P less than 0.05) faster onset of relief of symptoms compared with the group treated with clemastine. Concerning nasal stuffiness, loratadine was significantly (P less than 0.05) superior to clemastine after 1 week's treatment. Reports of adverse reactions showed that significantly (P less than 0.05) more patients complained of sedation in the clemastine than in the loratadine group. Regarding other adverse experiences and laboratory tests, the three treatment groups were statistically comparable (P less than 0.05). The study showed that compared with placebo both loratadine and clemastine were effective in relieving nasal and eye symptoms in patients with perennial allergic rhinitis. Loratadine was safe and well tolerated and was significantly less sedative than clemastine; loratadine may therefore possess an advantage in clinical use in the treatment of perennial allergic rhinitis.