Faster onset of action with topical levocabastine than with oral cetirizine

This international multicentre, open-label, parallel-group trial was undertaken to compare the therapeutic efficacy and tolerability of topical levocabastine and oral cetirizine in patients with perennial allergic rhinoconjunctivitis, with particular reference to the comparative onset of action of the two drugs. A total of 207 patients were randomized to receive either levocabastine nasal spray (0.5 mg/ml, two sprays in each nostril twice daily) plus levocabastine eye drops as required (0.5 mg/ml, one drop in each eye twice daily p.r.n.) or cetirizine orally (10 mg once daily) with a treatment duration of 2 weeks. Onset of action was found to be significantly more rapid with levocabastine than with cetirizine for both nasal and ocular symptoms (p < 0.001). Within 15 min of study drug administration, 36% of levocabastine-treated patients reported relief from nasal symptoms and 32% relief from ocular symptoms compared with 10% and 17% of patients on cetirizine, respectively. At 1 h, the percentages of patients reporting relief were 76% and 38% for nasal symptoms, and 81% and 48% for ocular symptoms in the levocabastine and cetirizine treatment groups, respectively. At 8 h there were no differences between the two treatments. Overall therapeutic efficacy was found to be comparable in the two treatment groups over the 2-week study period with no significant intergroup differences in symptom severity or global therapeutic efficacy. Both drugs were well tolerated with no significant differences in the incidence or type of adverse reactions between the two groups. In conclusion, levocabastine eye drops and nasal spray are as effective and well tolerated as oral cetirizine for the treatment of perennial allergic rhinoconjunctivitis with the advantage of a significantly faster onset of action for both nasal and ocular symptoms.     

Topical levocabastine-a review of therapeutic efficacy compared with topical sodium cromoglycate and oral terfenadine on days with high pollen counts

Levocabastine is a new H(1)-receptor antagonist specifically developed for the topical treatment of seasonal allergic rhinoconjunctivitis. Clinical experience to date clearly demonstrates that levocabastine eye drops and nasal spray are effective and well tolerated for the treatment of this allergic disorder. Analysis of data from a number of comparative trials reveals that topical levocabastine is at least as effective as sodium cromoglycate and the oral antihistamine terfenadine, even on days with high pollen counts (>/= 50 pollen particles/m(3) ) when symptoms are severe. Coupled with a rapid onset of action and twice daily dosing, these findings make topical levocabastine an attractive alternative to other therapeutic approaches as a first-line therapy for the treatment, of this common condition.     

Efficacy and tolerability of levocabastine and azelastine nasal sprays for the treatment of allergic rhinitis

Levocabastine and azelastine are currently the only antihistamines available as nasal sprays for the topical therapy of seasonal allergic rhinitis. The present study was undertaken to compare the onset of action, efficacy and tolerability of these two agents in a total of 242 patients with this condition. This was an international, multicentre, open-label, randomized, parallel-group trial with 123 patients treated with levocabastine (0.5 mg/ml, two puffs per nostril twice daily) and 119 with azelastine (1 mg/ml, one puff per nostril twice daily). Onset of action was comparable for the two drugs with over 50% of patients in each group reporting significant symptomatic relief within 30 min of administration of the first dose of study medication. Therapeutic efficacy was also found to be comparable in the two groups with no statistically significant intergroup differences reported for any of the parameters evaluated, although assessments of global therapeutic efficacy revealed a trend favouring levocabastine. Levocabastine appeared to be better tolerated than azelastine (p = 0.06), with the incidence of the most common adverse experiences, application site reactions and taste disturbances, significantly higher on azelastine than with levocabastine (5% versus 1%; p = 0.05 and 5% versus 0%; p = 0.01, respectively). In conclusion, levocabastine nasal spray appears to be at least as effective as, but better tolerated than, azelastine nasal spray for the treatment of seasonal allergic rhinitis.     

A review of the tolerability and safety of levocabastine eye drops and nasal spray. Implications for patient management

Levocabastine is a highly potent and selective H(1)-receptor antagonist specifically developed for topical administration by ocular and nasal routes. The clinical effects of levocabastine occur rapidly and are predominantly due to local antihistaminic effects at the site of application. Clinically, levocabastine is well tolerated with an adverse effect profile comparable with that of sodium cromoglycate and placebo. As might be expected from the route of drug administration, local irritation is the most frequent adverse event seen with levocabastine eye drops and nasal spray with an incidence comparable with that in placebo-treated controls. Intranasal application of levocabastine has been shown to have no adverse effect on ciliary activity both in vitro and in vivo, while ocular administration has not been shown to have any significant or consistent adverse effect in both animal and human studies. At therapeutic doses, levocabastine appears to be devoid of significant systemic activity producing no apparent effects on cardiovascular, psychomotor and cognitive function. Since levocabastine undergoes little hepatic metabolism, and only low plasma levels of the drug are attained following topical administration, drug interactions are unlikely.     

Treatment of allergic rhinoconjunctivitis: a review of the role of topical levocabastine

Lcocabastine is an extremely potent and highly selective H(1)-receptor antagonist which has been specifically developed as eye drops and nasal spray for the treatment of allergic rhinoconjunctivitis. Clinical experience to date suggests that this topical antihistamine is at least as effective as other current first-line therapeutic approaches for the treatment of this condition, including oral H(1)-receptor antagonists and sodium cromoglycate. Onset of action is rapid, with clinical effects apparent within minutes of instillation. Moreover, duration of action is sufficiently long to permit a convenient twice-daily dosing regimen. Topical levocabastine is well tolerated with an adverse-effect profile comparable with that of placebo and sodium cromoglycate. As might be expected from the route of drug administration, application site reactions are the most frequent adverse effect associated with levocabastine eye drops and nasal spray with an incidence comparable with that seen in placebotreated controls. The availability of effective and well-tolerated topical antihistamines, such as levocabastine, is an important advance which broadens the range of therapeutic approaches available for the clinical management of allergic rhinoconjunctivitis. Levocabastine appears to be an attractive alternative to oral antihistamines as a first-line therapeutic option for the treatment of this atopic condition.     

Morning versus evening dosing of desloratadine in seasonal allergic rhinitis: a randomized controlled study [ISRCTN23032971].

BACKGROUND: A circadian rhythm of symptoms has been reported in allergic rhinitis and some studies have shown the dosing time of antihistamines to be of importance for optimizing symptom relief in this disease. The objective of this study was to examine the efficacy of morning vs. evening dosing of the antihistamine desloratadine at different time points during the day. METHODS: Patients >/= 18 years, with seasonal allergic rhinitis received desloratadine 5 mg orally once daily in the morning (AM-group) or evening (PM-group) for two weeks. Rhinorrhea, nasal congestion, sneezing and eye symptoms were scored morning and evening. Wilcoxon rank sum and 2-way ANOVA test were used. RESULTS: Six-hundred and sixty-three patients were randomized; 336 in the AM-group; 327 in the PM-group. No statistically significant differences were seen between the AM and PM group at any time points. In the sub-groups with higher morning or evening total symptom score no difference in treatment efficacy was seen whether the dose was taken 12 or 24 hours before the higher score time. There was a circadian variation in baseline total symptom score; highest during daytime and lowest at night. The circadian variation in symptoms was reduced during treatment. This reduction was highest for daytime symptoms. CONCLUSIONS: A circadian rhythm was seen for most symptoms being more pronounced during daytime. This was less apparent after treatment with desloratadine. No statistically significant difference in efficacy was seen whether desloratadine was given in the morning or in the evening. This gives the patients more flexibility in choosing dosing time.     

儿童过敏性结膜炎与变应性鼻炎的相关性及鼻眼联合防治效果分析

目的：探讨儿童过敏性结膜炎与变应性鼻炎的相关性研究及鼻眼联合防治的临床效果。方法：回顾性分析300 例儿童过敏性 结膜炎与310 例儿童变应性鼻炎患者的临床资料,对儿童过敏性结膜炎与变应性鼻炎的相关性进行分析后将所有患儿随机均分 为对照组与观察组,对照组采用常规点眼的方法进行治疗,观察组则采用鼻朗喷鼻联合人工泪液点眼进行治疗。比较两组临床疗 效及不良反应情况。结果：（1）300 例过敏性结膜炎患儿中,50 例（16.67%）并发变应性鼻炎;310 例变应性鼻炎患儿中,59 例 （19.03%）并发过敏性结膜炎（P＞0.05）;（2）109 例同时并发两种疾病患儿中,均进行眼结膜与鼻粘膜的刮片检查嗜酸性粒细胞, 其中60 例（55.05%）结膜刮片与67 例（61.47%）鼻粘膜刮片检测到嗜酸性粒细胞（P＞0.05）;（3）两组治疗前后BUT 及角膜荧光素 染色评分、症状评分、临床总有效率比较差异明显（P＜0.05）。结论：儿童过敏性结膜炎与变应性鼻炎具有一定的相关性;鼻朗喷鼻 联合人工泪液点眼治疗儿童合并变应性鼻炎的临床疗效显著。     

Characteristics, clinical effect profile and tolerability of a nasal spray preparation of Artemisia abrotanum L. for allergic rhinitis.

A nasal spray formulation containing an extract of Artemisia abrotanum L. was developed for therapeutic use in patients with allergic rhinitis and other upper airway disorders. The nasal spray preparation used contains a mixture of essential oils (4 mg/ml) and flavonols (2.5 microg/ml), of which some components have been shown to possess antiinflammatory, expectorant, spasmolytic as well as antiseptic and antimicrobial activities. The most important constituents in the essential oil fraction of the preparation are 1,8-cineole, linalool and davanone, while the flavonol fraction contains centauredin, casticin and quercetin dimethyl-ethers. No trace of thujon was observed in the essential oil of the Artemisia abrotanum L. genotype "Tycho" used for the manufacture of the nasal spray preparation. In 12 patients with diagnoses of allergic rhinitis, allergic conjunctivitis and/or bronchial obstructive disease, the nasal spray was given immediately after the appearance of characteristic allergic nasal symptoms. In 10 of the 12 patients, allergic rhinitis with nasal congestion, sneezing and rhinorrhea was dominant. After administration of the nasal spray, all patients experienced a rapid and significant symptom relief of nasal symptoms, comparable to the effect of antihistamine and chromoglicate preparations which several of the patients had used previously. The effect was present within 5 minutes after the administration and lasted for several hours. In 7 of the 10 rhinitis patients with concomitant symptoms of allergic conjunctivitis, a significant subjective relief of eye symptoms was also experienced. In 3 of the 6 patients who had a history of characteristic symptoms of endogenous, exogenous or exercise induced bronchial obstructive disease, there was a bronchial symptom relief by the nasal spray preparation which was experienced as rapid and clinically significant. It is concluded from the present proof of concept study, that a nasal spray formulation containing an extract characterised by a mixture of essential oils and flavonols from the Artemisia abrotanum L. genotype "Tycho", appears to be clinically useful and suitable for the prophylactic and therapeutic management of patients with allergic rhinitis and adjuvant symptoms.     

Inter-Relationship between Rhinitis and Conjunctivitis in Allergic Rhinoconjunctivitis and Associated Risk Factors in Rural UK Children

Objective

Allergic conjunctivitis (AC) is a common condition, especially in childhood. The extent to which it occurs concurrently with or independently from allergic rhinitis (AR) has not been well described.

Aim

To examine the inter-relationship between rhinitis and conjunctivitis and the epidemiological risk factors for these conditions in a rural UK population.

Methods

Cross-sectional study of rural school children (aged 5–11 years). Parental questionnaires were used to diagnose allergic outcomes (including conjunctivitis, rhinitis and rhinoconjunctivitis), and to collect data on atopic history, demographic and environmental exposures. Odds ratios of allergic outcome by exposure were examined adjusted for age, sex, breastfeeding, family history of allergy, number of older and younger siblings.

Results

Prevalence of conjunctivitis was 17.5%, rhinitis 15.1% and rhinoconjunctivitis 13.0%. Seasonality of symptoms varied by condition: 64.7% of those with conjunctivitis had seasonal symptoms (April-Sept only), 46.7% of those with rhinitis and 92.2% of those with rhinoconjunctivitis. Living on a farm consistently reduced the risk of conjunctivitis (odds ratio 0.47, 95%CI 0.29–0.79, p = 0.004), rhinitis (OR 0.57, 95%CI 0.33–1.01, p = 0.05) and rhinoconjunctivitis (OR 0.57, 95%CI 0.32–1.03, p = 0.06). Exposure to farm animals (particularly in early life), current consumption of unpasteurised milk and playing in a barn or stable significantly reduced the risk of all three conditions.

Conclusion

More children had parent-reported conjunctivitis than rhinitis. The majority of children with either condition also reported symptoms with the other condition. Farmers’ children have less eye and/or nasal symptoms. A number of farming variables linked with the farm microbial environment are likely to be mediating the protective effect.     

季节因素对过敏性结膜炎就诊及用药的影响研究

目的:探讨过敏性结膜炎(AC)与抗过敏滴眼液用量间的关系,并分析季节因素对其产生的影响。方法:采用重力沉降法于2015年全年对北京城区主要气传花粉浓度进行监测,统计2015年我院变态反应科门诊AC就诊诊次及三种主要抗过敏滴眼液处方量,并采用Spearman相关性分析AC就诊诊次与抗过敏滴眼液用量间的关系。结果:2015年全年共监测花粉76164颗,花粉分布呈现春秋两季高峰,花粉分布最高的月份为4月(34.84%),其次为3月(29.72%),5月(10.87%),9月(10.52%),8月(9.94%);花粉分布最少的月份为1月和11月(0.11%)。春季花粉高峰期(3-5月份)月平均花粉数量为19150颗,秋季花粉高峰期(8-9月份)月平均花粉数量为7792颗,秋季花粉高峰期月平均花粉数量低于春季。2015年我院变态反应科AC月平均就诊诊次为(80.42±54.28)人次,8月份AC诊次最高,占全年的18.03%,其次为9月份(16.99%)、4月份(13.99%)、3月份(12.54%)、5月份(7.98%)。抗过敏滴眼液月平均用量为(148.67±148.63)瓶,8月份抗过敏滴眼液用量最高,占全年的28.25%,其次为3月份(17.21%)、9月份(14.18%)、4月份(13.11%)、5月份(8.30%),AC就诊次数及抗过敏滴眼液处方量均呈现春秋季节高峰。Spearman相关性分析显示,每月花粉量与AC就诊诊次、抗过敏滴眼液用量呈正相关(r=0.806,0.830,P=0.000,0.000),AC就诊诊次与抗过敏滴眼液用量呈正相关(r=0.923,P=0.000)。结论:花粉分布、AC诊次及抗过敏滴眼液用量均出现春秋季节高峰。秋季花粉致敏性高于春季花粉,用药及AC就诊最高峰均出现在秋季。     

Bronchial asthma in hay fever

The author diagnosed cough, emphysema and the symptoms characteristic for the bronchial asthma in 43% of patients with seasonal allergy (rhinitis, conjunctivitis) to pollens. Such symptoms were more frequent (51% of cases) in patients allergic to the grass pollens with coexisting hypersensitivity to Compositae family. Asthmatic symptoms in patients allergic only to grass pollens were seen in 38%. The author suggests that prolonged exposition in the inhalatory allergens (from two to four-five months) plays an important role in asthma onset in such patients. It rather delays than accelerates admittance to allergic clinics.     

Bilastine: new insight into antihistamine treatment

Bilastine is a new second generation H1-antihistamine recently approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU). Bilastine epitomizes the evolution of research on antihistamines concerning both efficacy and safety. In AR treatment, a number of large controlled clinical trials documented its efficacy, as assessed by improvement of all nasal and ocular symptoms and quality of life. These outcomes show that bilastine meets current EAACI/ARIA criteria for medications used in the treatment of AR. Also in CU, the review of the literature indicates that once-daily treatment with bilastine 20 mg was effective in managing symptoms and improving patient’s quality of life. Concerning safety and tolerability, the profile of bilastine is very similar to placebo and in particular the adverse effects on central nervous system are insignificant. The balance of efficacy and safety of bilastine is particularly helpful when dosages higher than standard are needed to control the symptoms, as frequently occurs in patients with urticaria, in whom antihistamines doses up to four times the standard dose may be administered.     

Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl

The current investigation aims to develop and evaluate novel ocular proniosomal gels of lomefloxacin HCl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Proniosomes were prepared using different types of nonionic surfactants solely and as mixtures with Span 60. The formed gels were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Only Span 60 was able to form stable LXN-proniosomal gel when used individually while the other surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span 60:Tween 60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80%), appropriate vesicle size (187?nm) as well as controlled drug release over 12?h. Differential scanning calorimetry confirmed the amorphous nature of LXN within the vesicles. Stability study did not show any significant changes in entrapment efficiency or vesicle size after storage for 3 months at 4?°C. P-LXN 7 was found to be safe and suitable for ocular delivery as proven by the irritancy test. The antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops.     

Preferential inhibition of human phosphodiesterase 4 by ibudilast

Ibudilast ophthalmic solution exhibited an improved clinical efficacy over cromoglycate in the treatment of allergic conjunctivitis. To further characterize its principal mode of action, the phosphodiesterase (PDE) inhibitory profile of ibudilast has been examined using human recombinant enzymes. Ibudilast, but not the other commonly used anti-allergic ophthalmic solutions including cromoglycate, ketotifen, tranilast and levocabastine, potently inhibits purified human PDE4A, 4B, 4C and 4D with IC50 values at 54, 65, 239 and 166 nM, respectively. Ibudilast effectively blocks lipopolysaccharide (LPS)-induced tumor necrosis factor (TNFalpha, IC50 = 6.2 microM) and N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene (LT) B4 biosynthesis (IC50 = 2.5 microM) in human whole blood, which are 3 and 6-fold more potent than cilomilast, respectively. The attenuated inflammatory and allergic responses from the potent and preferential PDE4 inhibition of ibudilast may have contributed significantly to its beneficial pharmacological responses and distinguishes ibudilast from the other ophthalmic solutions in the treatment of ocular allergy.     

Clinical evaluation of cetirizine

Efficiency of cetirizine--a new antihistaminic agent--was evaluated in 61 patients with seasonal rhinitis in placebo-controlled double-blind trial. Patients were randomly divided into subgroups. Cetirizine significantly inhibited the symptoms of allergic rhinitis and conjunctivitis. Adverse reactions were similar to those of placebo. Increased clinical efficiency but also an increase in adverse reaction incidence were noted when the drug was administered in the evening and not in the morning. High efficacy of placebo is worth mentioning. Therefore, antihistaminic agents should be tested in placebo-controlled double-blind trials.     

Secondary prevention of allergic symptoms in a dairy farmer by use of a milking robot

Background

Allergic sensitization and reactions to guinea pig (Cavia porcellus) have been well documented in laboratory animal handlers, primarily manifesting as rhinitis, conjunctivitis, and asthma. Severe allergic reactions, however, are rare.

Methods

We report two patients with severe allergic reactions following non-occupational exposure to guinea pigs. The first patient, an 11-year-old female, developed ocular, nasal, skin and laryngeal edema symptoms immediately after handling a guinea pig. The second patient, a 24-year-old female, developed symptoms of isolated laryngeal edema after cleaning a guinea pig cage. Percutaneous skin testing, RAST, ELISA and ELISA inhibition testing with guinea pig extract were performed.

Results

Both patients had IgE-mediated allergy to guinea pig confirmed by ELISA and either RAST or skin testing. ELISA inhibition studies confirmed the specificity of the IgE reactivity to guinea pig.

Conclusion

Severe IgE-mediated reactions can occur following non-occupational guinea pig exposure. Physicians should be aware of this possibility.     

Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study

Background

The classification of rhinitis in adults is missing in epidemiological studies.

Objective

To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach.

Methods

983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401).

Results

Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis.

Conclusion

This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables.     

Randomised double blind controlled clinical trial of intranasal budesonide in treatment of hay fever.

The effectiveness of budesonide, a new non-halogenated glucocorticoid administered by nasal inhaler, was evaluated in a double blind comparison with placebo in patients presenting with hay fever. Patients were supplied with antihistamine tablets and eye drops for use when they considered that their symptoms were inadequately controlled by their inhaler. Patients recorded the severity of their symptoms in a daily diary card and visited their general practitioner for assessment weekly for four weeks. All nasal symptoms of hay fever were appreciably reduced in the group taking budesonide and, although their eye symptoms were more severe than in the group taking placebo, they did not use appreciably more eye drops than the latter. The placebo group used appreciably more antihistamine tablets than those in the budesonide group. No patients were withdrawn from the budesonide group because of treatment failure or unacceptable side effects. The results suggest that budesonide is an acceptable and effective treatment for the nasal symptoms of hay fever.     

马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响

目的:探讨马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响。方法:选取2015年1月-2016年5月在我院接受治疗的原发性开角型青光眼患者84例,其中给予马来酸噻吗洛尔眼液治疗的42例记为对照组,给予拉坦前列素眼液联合马来酸噻吗洛尔眼液治疗的42例记为观察组,两组均治疗6个月。对比两组患者治疗过程中的眼压变化情况,并对比两组患者的临床总有效率、药物依从性和并发症情况。结果:观察组治疗2、4、6个月后的眼压均显著低于对照组(P0.05),观察组患者治疗6个月后与治疗前的眼压差值大于对照组(P0.05)。两组患者治疗2、4、6个月后的眼压呈下降趋势,两两比较差异均有统计学意义(P0.05)。观察组的临床总有效率95.24%显著高于对照组的80.95%(P0.05)。两组患者在治疗过程中结膜充血、眼内异物感、眼睛疼痛、视力模糊、味觉异常以及总并发症发生率对比差异不显著(P0.05)。观察组患者的药物依从性比例显著低于对照组(P0.05)。结论:马来酸噻吗洛尔眼液联合拉坦前列素眼液治疗原发性开角型青光眼患者具有较好的临床疗效,可显著降低患者眼压,同时具有较好的安全性,但药物依从性较差。