Dose-ranging study of fluticasone furoate nasal spray for Japanese patients with perennial allergic rhinitis

ABSTRACT

Background: This study was designed to evaluate the efficacy and safety of fluticasone furoate nasal spray (FFNS), a novel enhanced-affinity intranasal corticosteroid, in Japanese patients with perennial allergic rhinitis (PAR), and to determine the optimal dose.

Methods: In this phase II, multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study, 240 patients (aged ≥ 16 years) received once-daily (od) treatment for 2 weeks with either FFNS 110 μg (n = 80), 220 μg (n = 81) or placebo (n = 79). Patients evaluated 3 nasal symptoms using a 4-point scale. Efficacy was assessed as the mean change from baseline in total nasal symptom score (TNSS).

Results: Treatment with FFNS resulted in a significantly greater decrease over the treatment period in the mean 3TNSS (sneezing, rhinorrhea, and nasal congestion; p < 0.001 each dose vs. placebo), compared with placebo. More patients receiving FFNS had a markedly or moderately improved impression of treatment than placebo recipients (48% and 49% for FFNS 110 μg and 220 μg, respectively, vs. 18% for placebo; p < 0.001). Nasal rhinoscopy findings revealed significant improvements in mucosal swelling of the inferior turbinate (110 μg: p = 0.004; 220 μg: p = 0.011) and amount of watery rhinorrhea (110 μg: p = 0.003; 220 μg: p < 0.001), compared with placebo. Both doses of FFNS were well tolerated.

Conclusions: Both FFNS 110 µg and 220 µg od were effective in alleviating nasal symptoms in Japanese patients with PAR over the 2-week duration of this study. FFNS 110 µg od was selected as the optimal dose for further evaluation in phase III clinical trials.     

An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge

AIMS: To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. METHODS: Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 microg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25-800 mg ml-1) and histamine (0.25-8 mg ml-1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. RESULTS: There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI -0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. CONCLUSIONS: AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR.     

Effect of ipratropium on nasal reactivity to histamine and eosinophil influx in perennial allergic rhinitis

Summary In a double-blind, placebo-controlled study nasal saline and histamine provocation tests were performed in patients with perennial allergic rhinitis in order to assess changes in eosinophil influx and non-specific nasal reactivity after 8 days of treatment with ipratropium bromide. A “nasal pool” method was used to trace changes in protein level and eosinophil influx into nasal secretions. Treatment with ipratropium 80 mg q.i.d. caused a significant decrease in the albumin and total protein level in saline washings and induced a five-fold increase in eosinophils as compared to the placebo treatment. The nasal mucosal response to histamine, assessed as the number of sneezes and protein level, was more responsive to ipratropium treatment than the mucosa from placebo-treated subjects. Since eosinophil numbers were correlated with an increase in the vascular and sneezing responses, it appears that ipratropium potentiates inflammatory mechanisms when used in subjects with an allergy in the nasal mucosa.     

Desloratadine and levocetirizine improve nasal symptoms, airflow, and allergic inflammation in patients with perennial allergic rhinitis: a pilot study

BACKGROUND: Nasal obstruction is the main symptom in patients with perennial allergic rhinitis. Some new antihistamines have been demonstrated to be capable of improving this symptom. OBJECTIVE: The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, eosinophils, and IL-4 in patients with perennial allergic rhinitis, before and after treatment with two new antihistamines: desloratadine and levocetirizine. METHODS: Thirty patients with perennial allergic rhinitis were evaluated, 26 males and 4 females (mean age 26+/-7.1 years). All of them received either desloratadine (5 mg/daily) or levocetirizine (5 mg/daily) or placebo for 4 weeks. The study was double-blind, parallel-group, placebo-controlled, and randomized. Total symptom score (including: rhinorrhea, nasal itching, sneezing, and nasal obstruction) was assessed before and after treatment. Rhinomanometry and decongestion test, nasal lavage, and nasal scraping were performed in all subjects before and after treatment. Eosinophils were counted by conventional staining; IL-4 was measured by immunoassay of fluids recovered from nasal lavage. RESULTS: Desloratadine and levocetirizine treatment induced significant symptom relief and significant reduction of IL-4. Both antihistamines significantly affected all parameters in comparison with placebo. CONCLUSIONS: This pilot study demonstrates the effectiveness of antihistaminic treatment in: i) relieving nasal symptoms, including obstruction, ii) improving nasal airflow, iii) exerting decongestant activity, iv) reducing eosinophil infiltration, and v) diminishing IL-4 levels.     

Once-daily immediate-release fexofenadine and sustained-release pseudoephedrine combination: a new treatment option for allergic rhinitis

Allergic rhinitis symptoms, in particular nasal congestion, can have a significant impact on patient quality of life, resulting in reduced productivity and daytime sleepiness. Newer-generation antihistamines are commonly used to treat allergic rhinitis; however, in patients with severe congestion, a combination of a newer-generation antihistamine and a decongestant is particularly beneficial. A new once-daily fexofenadine/pseudoephedrine combination has been developed and recently approved in the US. The combination provides an effective, well-tolerated antihistamine and a reliable, sustained-release pseudoephedrine system. In addition, small tablet size and once-daily dosing may provide patients with increased convenience and improve adherence. In summary, the combination of immediate-release fexofenadine/sustained-release pseudoephedrine offers an important additional option for the treatment of allergic rhinitis.     

Efficacy and long-term safety of mometasone furoate nasal spray in children with perennial allergic rhinitis

Abstract

Background:

Allergic rhinitis (AR) affects up to 40% of children by age 6 years. Perennial AR (PAR) causes sleep disturbance, diminishes concentration in school, impairs psychosocial functioning, and reduces quality of life. This study evaluated efficacy and long-term safety of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) in children with PAR.     

甘辛鼻腔用喷雾剂对豚鼠超敏鼻炎的治疗作用

目的:观察甘辛鼻腔用喷雾剂对豚鼠超敏性鼻炎的疗效.方法:采用甲苯-2-4-二异氰酸酯(TDI)诱导豚鼠超敏性鼻炎反应模型,实验一选择30只模型动物随机分为2组,观察给药组和空白对照组豚鼠鼻黏膜组织的病理变化.实验二选用健康豚鼠50只,随机分为5组,其中1个组为健康受试组,另外4组通过TDI诱导造成豚鼠超敏性鼻炎反应模型.以迪通鼻炎水(市售)为阳性药物,观察健康受试组、给药组(高、低剂量组,每次每侧用10,5μL,bid)、阳性对照组、空白对照组的豚鼠鼻黏膜组织病理变化.结果:实验一中给药组与空白组相比豚鼠鼻黏膜上皮下嗜酸性粒细胞、淋巴细胞、浆细胞浸润显著减少,腺体增生也显著减少(P<0.01).实验二中高、低2个剂量组均使豚鼠鼻黏膜上皮下嗜酸性粒细胞、淋巴细胞、浆细胞和嗜中性粒细胞显著减少,腺体增生和分泌亢进得到有效的抑制,疗效与阳性对照组相似.结论:甘辛鼻腔用喷雾剂可有效抑制超敏反应过程,保护鼻黏膜.     

聚焦超声或射频治疗常年性过敏性鼻炎88例疗效观察

目的比较聚焦超声与射频治疗常年性过敏性鼻炎的疗效。方法88例过敏性鼻炎患者随机分为2组,聚焦超声治疗组45例,射频治疗组43例。2组患者通过对鼻中隔前上方、鼻丘或下鼻甲前方黏膜进行聚集超声或射频治疗,并比较2组疗效。结果2组治疗后,临床症状均明显改善,且聚焦超声组改善更为明显;聚焦超声组治疗前症状体征评分为（11.25±2.38）分,治疗后评分为（4.53±3.21）分,差异有统计学意义（P〈0.05）;治疗后随访1年,聚焦超声治疗组总有效率为91.1%,射频治疗组总有效率为74.4%,差异有显著统计学意义（P〈0.01）。结论聚焦超声治疗常年过敏性鼻炎,疗效好、安全性高、方法简单,术后反应轻、恢复快。     

左旋多巴激发试验在生长发育迟缓儿童中的临床价值

目的探讨左旋多巴激发试验在生长发育迟缓儿童中的临床价值。方法对生长发育迟缓儿童采用左旋多巴激发试验,生长激素测定采用化学发光法。结果(1)生长激素的峰值在左旋多巴激发后30和60 m in出现最多(P<0.01);(2)生长激素完全缺乏者占29.8%,部分缺乏占55.3%,而完全不缺乏者仅占14.9%。结论儿童生长发育迟缓大多数是由于生长激素缺乏或部分缺乏所致。左旋多巴激发试验可作为临床诊断侏儒症的方法之一。     

Comparison of pseudoephedrine and triprolidine, alone and in combination in preventing nasal congestion in subjects with allergic rhinitis using nasal histamine challenge.

The abilities of triprolidine 2.5 mg and pseudoephedrine 60 mg, alone and in combination, to protect against an increase in nasal airway resistance (NAR) after histamine challenge were determined in eighteen individuals with grass pollen allergy. The study was conducted outside the pollen season using a double-blind, placebo controlled crossover design. The prior administration of pseudoephedrine 60 mg and triprolidine 2.5 mg alone or in combination was superior to placebo in reducing the increase in NAR after challenge with 1.0% histamine. However, such NAR measurements did not differentiate between pseudoephedrine 60 mg and triprolidine 2.5 mg administered alone or in combination. Challenge with 0.1% histamine failed to discriminate between any of the test medications.     

Single-dose and steady-state bioequivalence of fexofenadine and pseudoephedrine combination tablets compared with individual formulations in healthy adults

ABSTRACT

Objective: A 24-h extended-release formulation of fexofenadine HCl 180?mg/pseudoephedrine HCl 240?mg (FEX 180?mg/PSE 240?mg) has recently been approved by the US Food and Drug Administration for symptom relief of seasonal allergic rhinitis, including nasal congestion. When considering a combination formulation, it is important to confirm that the metabolism and pharmacokinetics of the drugs remain unchanged when combined. Thus, the aim of this study was to evaluate single-dose and steady-state bioequivalence of FEX 180?mg/PSE 240?mg 24-h compared with the individual formulations taken concurrently.

Research design and methods: This was an open-label, randomized, two-treatment, two-period, 10-day, crossover study. In Treatment A, healthy subjects received a single, oral dose of FEX 180?mg/PSE 240?mg combination tablet on Day 1 followed by 6 days of once-daily dosing beginning on Day 4. Participants in Treatment B were concurrently administered a single oral dose of FEX 180?mg immediate-release tablet and a PSE 240?mg extended-release tablet with a similar dosing schedule. After an 8-day washout period, subjects crossed over to the alternate treatment. Plasma concentrations of FEX and PSE were determined using high-performance liquid chromatography/mass spectrometry.

Results: Pharmacokinetic parameters AUC(0?∞)₁ and C_max1 following a single-dose (Day 1, dose 1), C_max7, AUC(0?24)₇ at steady-state and C_min7 measured at the end of the dosing interval (Day 9, dose 7) revealed bioequivalence between FEX 180?mg/PSE 240?mg combination tablet and the individual components taken concurrently. The 90% confidence intervals for the treatment ratios fell entirely within the bioequivalence range (80% to 125%). The combination tablet was well tolerated by all subjects, with a safety profile comparable to the individual components.

Conclusions: These findings demonstrate that the pharmacokinetics of the new 24-h FEX 180?mg/PSE 240?mg combination formulation are bioequivalent to the concurrent administration of the individual drug components. Furthermore, both treatments were well tolerated in this population.     

氮斯汀喷鼻剂治疗常年性变应性鼻炎随机双盲试验

目的 :探讨氮斯汀喷鼻剂治疗常年性变应性鼻炎的疗效及安全性。方法 :38例中、重度常年性变应性鼻炎病人行随机、双盲、对照研究。分氮斯汀组 19例 ,给予氮斯汀液体喷鼻剂喷鼻 ,每日 2次 ,每次每侧鼻孔 1揿 (每揿 140 μg氮斯汀 ) ,治疗 4wk。左卡巴斯汀组 19例 ,用左卡巴斯汀喷鼻剂喷鼻 ,每日 2次 ,每次 2揿 ,作为对照。治疗 2wk末及 4wk末时 ,根据主观评分及客观检查结果 ,综合评定疗效。结果 :氮斯汀喷鼻剂组总有效率为 95 % ,左卡巴斯汀喷鼻剂组为 84 % (P >0 .0 5 )。 2组治疗前后喷嚏、流涕、鼻痒、鼻塞及眼部症状积分下降分别为 1.4± 0 .8和 1.3± 1.0 ,1.0±0 .7和 0 .8± 0 .9,1.3± 0 .6和 1.4± 0 .7,0 .7± 0 .7和 0 .7± 0 .8,0 .8± 0 .8和 0 .5± 0 .7(均P >0 .0 5 ) ,未发生严重的不良反应。结论 :氮斯汀喷鼻剂与左卡巴斯汀喷鼻剂在治疗常年性变应性鼻炎时具相似的疗效和安全性     

儿童矮小症生长激素激发试验结果及护理

目的探讨适合身材矮小患儿有效、简单而可靠的生长激素（GH）激发试验的方法及减少其不良反应的护理。方法收集2010年8月—-2013年2月安徽医科大学第一附属医院儿科的矮小症住院患儿71例,予左旋多巴联合精氨酸行生长激素激发试验,并加强试验前、试验中、试验后的护理及健康指导。结果71例共497次静脉采血全部顺利完成,均未发生严重的不良反应。结论左旋多巴口服联合精氨酸静脉滴注进行生长激素激发试验方法简单,有效的护理可预防和减轻试验过程的不良反应,是顺利完成生长激素激发试验的保障。     

滴通鼻炎水喷雾剂治疗伤风鼻塞(急性鼻炎)的临床研究

目的:对滴通鼻炎水喷雾剂治疗伤风鼻塞(急性鼻炎)的临床疗效和安全性做出客观评价。方法:采用随机、盲法、阳性药平行对照、多中心试验的设计方法。本试验共入组伤风鼻塞患者88例,其中试验组66例,对照组22例,分别使用滴通鼻炎水喷雾剂,外用喷鼻,一次1~2揿,一日3~4次;鼻炎滴剂(喷雾型),外用喷鼻,一次1~2揿,一日3~4次。疗程均为5 d。用伤风鼻塞(急性鼻炎)临床疗效判定标准、局部症状、体征疗效和鼻塞缓解时间及维持时间评定疗效,一般体格检查、不良事件评定安全性。结果:88例患者治疗5 d后伤风鼻塞(急性鼻炎)的临床疗效:试验组的痊愈率为24.24%,显效率为31.82%,有效率37.88%,无效率6.06%;对照组的痊愈率为4.55%,显效率为36.36%,有效率36.36%,无效率22.73%。经CMH检验,两组的差异有统计学意义(P<0.05),试验组优于对照组。经秩和检验,两组的鼻塞缓解时间差异无统计学意义。经t检验,两组的鼻塞缓解维持时间差异有统计学意义(P<0.05),试验组优于对照组。两组治疗前后的体温、呼吸、心率、收缩压、舒张压等生命体征检查比较上,差异均无统计学意义。两组均无不良事件发生。结...     

复方苍耳子滴鼻剂对豚鼠变应性鼻炎的影响

目的观察复方苍耳子滴鼻剂对变应性鼻炎模型豚鼠症状的变化和血清组胺含量的影响。方法以甲苯-2,4-二异氰酸甲苯酯(TDI)作为致敏因子建立豚鼠鼻黏膜变态反应模型,以模型组、阳性药物组与空白组为对照,测定各组豚鼠鼻黏膜内组胺的含量及形态组织学的改变。结果 ①鼻部症状的改善情况:复方苍耳子滴鼻剂高、低剂量组药前总评分与药后总评分比较差异有统计学意义(P<0.05),能显著性改善慢性鼻炎模型动物的整体症状;②对血清组胺含量的影响:复方苍耳子滴鼻剂高、低剂量组血清组胺含量均显著低于模型组(P<0.05或0.01),能显著降低慢性鼻炎模型动物的血清组胺含量;③形态组织学的改变:复方苍耳子滴鼻剂高、低剂量对鼻黏膜上皮化生、腺体增生、血管增生或扩张及炎性细胞等方面均能显著改善慢性鼻炎模型动物的形态组织学。结论复方苍耳子滴鼻剂对豚鼠实验性变态反应性鼻炎有显著的改善作用。     

Fluticasone furoate nasal spray consistently and significantly improves both the nasal and ocular symptoms of seasonal allergic rhinitis: a review of the clinical data

Background: Allergic rhinitis (AR) is a highly prevalent disorder, which often manifests as both nasal (congestion, sneezing, itching and rhinorrhoea) and ocular (redness, watery eyes, itching and burning) symptoms. Until recently, efficacy against the ocular symptoms of AR has been inconsistent for any single intranasal corticosteroid (INS). Fluticasone furoate is an enhanced-affinity glucocorticoid with potent anti-inflammatory activity. Objective: To assess better the efficacy of an INS in the treatment of both the nasal and ocular symptoms of seasonal AR (SAR). Methods: Data from all four trials of fluticasone furoate nasal spray (FFNS) in the treatment of SAR are reviewed and critically considered. Results: FFNS consistently and significantly improved the nasal and ocular symptoms of SAR in patients sensitised to several different seasonal allergens (grass, ragweed and mountain cedar pollen) in all trials. An integrated analysis of the results also confirmed improvements in both nasal and ocular symptom scores in previously under-represented adolescent patients treated with FFNS. Conclusion: FFNS is the first INS to show consistent nasal and ocular efficacy across all SAR trials.     

蛋白激酶C、Bcl-2及Bax在变应性鼻炎鼻黏膜中的表达及意义

目的探讨变应性鼻炎（AR）患者鼻黏膜蛋白激酶C（PKC）、抗凋亡基因Bcl-2及促凋亡基因Bax蛋白的表达水平,以进一步了解AR的发病机制。方法应用免疫组织化学的方法检测26例AR患者（AR组）鼻黏膜及10例下鼻甲组织中（对照组）PKC、Bcl-2及Bax的表达。结果PKC、Bcl-2及Bax在2组中均有表达,AR组中PKC主要表达在嗜酸粒细胞、血管内皮细胞及腺体细胞,Bcl-2蛋白主要表达于鼻黏膜腺体细胞和上皮层,与对照组相比差异有统计学意义（P〈0.01）。Bax蛋白与Bcl-2蛋白表达部位一致,2组表达水平差异无统计学意义（P〉0.05）。结论AR鼻黏膜蛋白激酶C、抗凋亡基因Bcl-2蛋白表达上调,是AR嗜酸粒细胞增多、鼻分泌物增多及鼻黏膜上皮破坏的机制之一。     

Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis

Summary

The efficacy and safety of the nasally administered histamine H₁ receptor blocking drug azelastine was investigated in a randomized comparative trial with ebastine. Patients were treated for 14 days and efficacy was assessed by the physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was measured on the basis of reported adverse events. Data from a total of 59 patients were included in the efficacy analysis. Both treatment groups had dramatic reductions in the physician's total symptom score following treatment. Mean scores in the azelastine group decreased from 12.4 pretreatment to 5.6, while the mean ebastine scores decreased from 13.6 to 6.6. There was no significant difference between the two groups (p= 0.86). Changes in individual rhinitis symptoms showed no differences between the two groups. The majority of patients in both treatment groups reported an initial relief of symptoms within 1?h of dosing. For seven patients treated with azelastine, the initial effect was already seen after 10?min (ebastine: two patients). Eight adverse events were reported in each treatment group; all were mild except one report of sedation in an ebastine patient, which was of moderate severity. Three patients reported somnolence during treatment with ebastine. A bitter taste was mentioned by four patients in the azelastine group, but neither somnolence nor sedation was reported with azelastine. In conclusion, the results of the study suggest that both azelastine and ebastine are effective treatments of the symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.     

Maximal nasal inspiratory flow rate: Its use in assessing the effect of pseudoephedrine in vasomotor rhinitis

Summary The maximal nasal inspiratory flow rate has been used as an objective test to assess the effect of pseudoephedrine in patients with vasomotor rhinitis. In a double blind trial oral pseudoephedrine (60 mg) was shown to produce a significant increase in maximal nasal flow when compared with the effect of a placebo. The improvement seen after pseudoephedrine was comparable to that seen after the installation of ephedrine nose drops.     

The effects of histamine and leukotriene receptor antagonism on nasal mannitol challenge in allergic rhinitis

AIMS: It is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus. METHODS: A double-blind, randomized, placebo-controlled, crossover design was employed. Nine patients with allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg, montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal peak inspiratory flow recordings over 60 min. The change in peak nasal inspiratory flow was calculated as percentage change from baseline as the peak response and area under the time-response curve (AUC). RESULTS: Desloratadine and montelukast conferred a significant degree of protection compared to placebo for peak and AUC response, but there were no significant differences between the two drugs. For the peak response as percentage fall, the mean difference (95% CI) vs placebo was 27.7 (8.0, 47.4)% for desloratadine and 17.6 (1.9, 33.3)% for montelukast. CONCLUSIONS: Our results suggest that histamine and cysteinyl-leukotrienes are involved in mediating the response to nasal mannitol in allergic rhinitis.