瞬时受体电位在上气道高反应疾病神经免疫通路中的作用

临床非特异性冷热刺激诱发无变应原者上气道高反应表现、加重变应性鼻炎患者相关症状，依赖现有免疫药物治疗效果不佳，上述问题在临床顽固存在但尚无有效解决方案。瞬时受体电位(TRP)在上气道高反应(AHR)疾病中的发现为其提供了新思路。神经-免疫通路是AHR发病机制的重要构成，TRP的表达和激发与其有着密不可分的关系，相关研究最终会阐明此类症状具体的发病机制，成为未来临床治疗及干预的新方向。本综述突出了AHR神经免疫通路发病机制的重点构成及相关TRP通道的作用，且TRP亚家族TRPV1及TRPA1相关阻滞剂正逐步进入临床，TRP亚家族TRPV4、TRPM8有望成为药物研究新热点。     

非变应性高反应性鼻病的临床分型和治疗探讨

非变应性高反应性鼻病是指鼻腔黏膜对某些刺激因子，如变应原、寒冷、饮食、气味、空气污染等反应过强、超出正常生理状态的一类疾病。由于刺激因子不同和发病机制的差异，临床表现为鼻痒、喷嚏、流清涕和鼻塞等症状患者，除确诊为变应性鼻炎（AR）患者外，还发现不少为非变应性鼻炎（NAR）患者，临床将这两种表现相似的疾病，统称为高反应性鼻病。本文总结了2010年我院收治的非变应性高反应性鼻病患者的临床资料，对非变应性高反应性鼻病的临床分型和治疗进行分析报道。     

血红素加氧酶-1：一种治疗变应性鼻炎的新靶位

变应性鼻炎是耳鼻咽喉科最常见的疾病之一,是由Th2型免疫主导的鼻腔黏膜的Ⅰ型变态反应性疾病,是鼻腔黏膜的高反应性疾病。临床上以鼻塞、鼻痒、喷嚏、流清涕和鼻黏膜肿胀为主要特点。变应性鼻炎的发病率有全球性逐年增加的趋势,平均发病率为10％～25％。它可诱发或并发支气管哮喘、鼻窦炎、鼻息肉、中耳炎和变应性结膜炎等,严重影响患者的生活和工作。目前尚缺乏有效的治疗,尽管药物、物理和手术治疗等取得很大进展,     

鼻内镜下手术治疗鼻高反应性疾病进展

鼻高反应性疾病在临床上主要包括变态反应性鼻炎和血管运动性鼻炎。目前大多数患者经过规范化药物治疗症状可以控制,但仍有部分患者症状持续存在或频繁发作,严重影响患者的生活质量。近年来,随着鼻内镜技术的发展,一些学者开始尝试通过内镜下手术治疗鼻高反应性疾病,且取得了较好的疗效。现就手术的适应证、手术方式、疗效、评价标准、并发症等进行综述。     

儿童变应性鼻炎治疗中的药物选择和疗程依据

药物治疗是变应性鼻炎(AR)最重要的治疗手段之一.儿童AR的治疗原则与成人相同,但应特别注意各类药物的适用年龄、推荐剂量和不良反应.目前临床常用的AR治疗药物包括:口服或鼻用抗组胺药物(H1受体拮抗剂)、鼻用糖皮质激素、抗白三烯药(白三烯受体拮抗剂)、色酮类药物和鼻用减充血剂等.根据变应性鼻炎及其对哮喘的影响(allergic rhinitis and its impact on asthma,ARIA)指南(2008)[1],这些药物均适用于间歇性AR和轻度持续性AR的临床治疗,而对于中-重度持续性AR,则首选鼻用糖皮质激素.     

辣椒辣素治疗高反应性鼻病的疗效观察

高反应性鼻病是指鼻黏膜对某些刺激因子，如变应原、寒冷、饮食、气味、空气污染等反应过强，超出正常生理状态的一类疾病。由于刺激因子不同和发病机制的差异，临床上可有多种表现形式，包括变应性鼻炎(又分为季节性和常年性变应性鼻炎)、非变应性鼻炎伴嗜酸粒细胞增多综合征(nonallergic rhinitis eosinophilia syndrome，NARES)、     

翼腭窝封闭治疗高反应性鼻病

1993至1997年我院用利多卡因和地塞米松经翼腭管封闭蝶腭神经节治疗高反应性鼻病(主要为变应性鼻炎和血管运动性鼻炎)60例,效果良好,报道如下.     

鼻内镜下高选择性翼管神经切断术治疗难治性鼻黏膜高反应性疾病的临床研究

目的 分析鼻内镜下高选择性翼管神经切断术治疗难治性鼻黏膜高反应性疾病的有效性及安全性。方法 收集2019年1月—2021年3月门诊就诊的难治性变应性鼻炎(AR)及血管运动性鼻炎(VMR)并同意行高选择性翼管神经切断术的患者为研究对象,进行鼻内镜下双侧高选择性翼管神经切断术,术后进行定期随访,分别记录患者术前及术后1、3、6、12个月时鼻眼部、哮喘症状评分、鼻结膜炎生活质量评分、用药评分的变化,并记录术后并发症的发生情况。结果 随访结束时临床资料完整的患者共35例,术后 1、3、6、12个月时鼻部、眼部症状总评分、哮喘总评分、症状总评分、生活质量评分、用药评分均较术前降低,差异均具有统计学意义(P均＜0.001);1例患者术后出现单侧鼻腔出血,另1例患者术后出现短暂的头痛,所有患者随访期间均未出现眼干、眼异物感、上腭麻木感、萎缩性鼻炎等并发症。结论 鼻内镜下高选择性翼管神经切断术可以有效改善顽固性鼻黏膜高分泌及高敏感状态,提高患者生活质量,同时避免了翼管神经切断术后干眼的缺点,并发症少,是治疗难治性鼻黏膜高反应性疾病的一种安全有效的手段。     

国家级继续医学教育项目《高反应性鼻炎治疗新进展》和《头颈肿瘤诊治新进展》培训班通知

<正>由桂林医学院附属医院主办的国家级继续医学教育项目《高反应性鼻炎治疗新进展》(批准号:2014-07-01-118国)和《头颈肿瘤诊治新进展》(批准号:2014-07-01-119国)学习班将于2014年7月24—27日在桂林医学院附属医院举办。本学习班讲授的主要内容有:对高反应性鼻炎的认识,变应性鼻炎的鼻用糖皮质激素治疗,变应性鼻炎     

微波热凝筛前神经、鼻丘、翼管神经治疗高反应性鼻炎

自1998年3月起我们用微波治疗高反应性鼻炎,效果满意,报告如下. 1　资料与方法 1.1　临床资料高反应性鼻炎20例中,男9例,女11例,16～55岁,平均25岁,病程1～8年,平均2年.患者均有鼻痒、喷嚏、流清涕史,多数患者有长期服药和局部用药史.     

Expression and localization of TRPV1 in human nasal mucosa

Capsaicin is the pungent principle in chili peppers and previous studies reported that topical application of capsaicin to patients with allergic and non-allergic rhinitis produced significant and long-lasting relief of symptoms. The capsaicin receptor (TRPV1, VR1) is a nociceptive transducer and the existence of TRPV1 in non-neuronal cells as well as neuronal cells has been reported. In order to clarify the role of TRPV1 on the upper airway, we examined the localization and the expression of TRPV1 in human nasal mucosa. Surgically obtained human nasal specimens were processed for immunohistochemistry with commercial anti-TRPV1 antibody. We also performed immunofluorescence with anti-TRPV1 antibody and anti-neurofilament antibody or anti-CD31 antibody. Epithelial cells and vascular endothelial cells were cultured from nasal turbinates, respectively. For RT-PCR analysis, total RNA was isolated, and then RT-PCR was performed. Immunohistochemical studies revealed that TRPV1 positive cells were found on epithelial cells, vascular endothelial cells, submucosal glands and nerves in human nasal mucosa. By RT-PCR analysis, the mRNA expression of TRPV1 was confirmed in human nasal mucosa. These results suggest that capsaicin can directly influence the epithelial secretory and various functions via TRPV1 as well as the activation of the sensory neurons.     

The relationship between the number of the autonomic nerve receptors and degree of hyperreactive nasal symptoms in patients with hyperesthetic rhinitis

It is generally accepted that abnormal autonomic responsiveness may contribute to the pathogenesis of hyperesthetic rhinitis. Histologically, in the nasal mucosa, cholinergic fibers are found close to blood vessels, but are particularly numerous around the glands. Adrenergic fibers are found mainly around the vascular structures. Physiological and pharmacological studies demonstrate that parasympathetic hypersensitivity causes hypersecretion, and sympathetic hyposensitivity causes vasodilatation. alpha 1-adrenergic receptor function is dominant for this vasodilatation. Using radioligand binding techniques, it has been found that there is an increased number of muscarinic cholinergic receptors and a decreased number of alpha 1- and beta-adrenergic receptors in patients with nasal allergy, while the binding affinities do not change. In this report, using radioligand binding techniques, we investigated the relationships between the number of receptors and the degree of the hyperreactive nasal symptoms in patients with hyperesthetic rhinitis. The results are as follows. 1. The number of muscarinic cholinergic receptors of human nasal mucosa in patients with hyperesthetic rhinitis was related significantly (P less than 0.01) to the degree of hypersecretion induced by methacholine and frequency of blowing nose estimated from allergy diary. 2. There was no relationship between frequency of sneezing and the number of muscarinic cholinergic receptors. 3. The number of alpha 1-adrenergic receptors was related significantly (P less than 0.05) to the degree of swelling of nasal mucosa induced by methoxyamine. Judging from these results, it was assumed that pathogenesis of hyperreactive nasal symptoms may be associated at least partially to the changes of number of autonomic nerve receptors in the nasal mucosa.     

Rhinobronchial syndrome: pathogenesis and correlation with allergic rhinitis in children

AIM: In the rhinobronchial syndrome a direct causal relationship exists between local nasal irritation and bronchopulmonary disease. Although allergic rhinitis has often been associated with lower airway hyperresponsiveness, no direct relationship between the two has been shown to date. The aim of this study was to determine the role of allergic rhinitis in the pathogenesis of the rhinobronchial syndrome in children by evaluating the effect of topical nasal treatment on lower airway hyperresponsiveness. MATERIALS AND METHODS: A total of 168 children presenting with aeroallergy and nasal disease associated with bronchopulmonary disease (asthma, chronic cough, bronchopulmonary infection) were evaluated at baseline and at 1 year of follow-up. Nearly half (83) were noted to have signs of allergic rhinitis and were treated with topical nasal medications (cortisones and antihistamines). Changes in upper and lower airway diseases were evaluated and potential causal relationships established. RESULTS: Allergic rhinitis treatment improved nasal disease symptoms in 67 (80.7%) patients; partial remission or lower healing rates were found in those with asthma (16.4%) and chronic cough (11.1%). CONCLUSIONS: Although often associated with lower airway hyperresponsiveness, allergic rhinitis in children does not appear to be a pathogenetic factor, as confirmed by the scarce effect the nasal treatment had on the bronchopulmonary disease. Instead, the frequent co-existence of nasal and bronchial symptoms may come under the concept of global allergy of the airways.     

经蝶窦黏膜下单侧翼管神经切断术治疗鼻黏膜高反应性疾病疗效分析

目的 分析总结经蝶窦黏膜下单侧翼管神经切断术治疗鼻黏膜高反应性疾病的安全性及有效性.方法回顾性分析陕西中医药大学第二附属医院耳鼻咽喉科2018年10月～2019年7月间采用经蝶窦黏膜下单侧翼管神经切断术治疗鼻黏膜高反应性疾病患者的临床资料.通过临床症状、鼻内镜检查、鼻窦CT及变应原检查,明确相关并发疾病及鼻黏膜高反应性...     

Neuronal markers in allergic rhinitis: expression and correlation with sensory testing

INTRODUCTION: Although the role of immunoglobulin E-mediated hypersensitivity reactions in allergic rhinitis is well known, the relative contribution of sensory nerves to the symptoms of rhinitis is uncertain. This study looked at the level of specific neuronal markers including the nerve marker protein gene product 9.5 (PGP 9.5), sensory and autonomic neuropeptides, the capsaicin/heat receptor TRPV1, and nerve growth factor (NGF) in patients with allergic rhinitis and controls and their correlation with nasal sensitivity. MATERIALS AND METHODS: Forty patients (23 controls, 17 rhinitis) having nasal surgery were recruited. Nasal sensitivity was tested using graded monofilaments. Inferior turbinate biopsies were collected and studied using immunohistology, with measurement of nerve fibers by direct observation or computerized image analysis. RESULTS: Nerve fibers (PGP 9.5) in the epithelium, subepithelium, and glandular/vascular regions were significantly increased in allergic rhinitis (P=.037, <.01, and .04, respectively), as were subepithelial and glandular/vascular fibers immunoreactive for neuropeptide substance P (P=.04 subepithelium; .02 glandular/vascular) and neuropeptide tyrosine (P<.01 glandular/vascular), markers for sensory and sympathetic nerves, respectively. TRPV1 epithelial fiber counts were higher in rhinitis, but this was not statistically significant. Epithelial NGF immunoreactivity (% area) was significantly increased in rhinitis (P=.027). Nasal sensitivity was correlated significantly with PGP 9.5 subepithelial innervation (control touch P=.023, irritation P=.046; rhinitis touch P=.042, irritation P=.043). A correlation was also observed between epithelial NGF and subepithelial PGP 9.5 innervation, which included all subjects (P=.044). CONCLUSION: The increased number and specific phenotypical changes of sensory nerves may play a role in nasal hypersensitivity and provide new targets for the treatment of rhinitis.     

The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.     

IgE-mediated reactions and hyperreactivity in pregnancy rhinitis.

OBJECTIVES: To determine whether respiratory allergy or hyperreactive nasal mucosa is exceptionally common in women with pregnancy rhinitis, and to evaluate other possible risk factors such as clinical asthma or rhinitis, smoking, age, parity, and sex of the child. PATIENTS AND METHODS: From an antenatal questionnaire study, 165 women, 83 (50%) of whom had had pregnancy rhinitis, were examined 6 months after delivery, and multiple antigen simultaneous testing chemiluminescent assay (MAST CLA) (10 airborne allergens) was performed. After histamine provocations, rhinostereometry and acoustic rhinometry were performed in 25 of them. Serum levels of soluble intercellular adhesion molecule-1 were determined 4 times during and once after pregnancy in 5 women with pregnancy rhinitis and 17 without pregnancy rhinitis. RESULTS: Thirty-nine women (24%) were sensitized to 1 or more allergen. The pregnancy rhinitis group showed significantly higher levels of IgE to house dust mites. There were also more smokers in the pregnancy rhinitis group. Clinical asthma or rhinitis, age, parity, and sex of the child did not differ significantly between the 2 groups. Mucosal swelling increased with rising concentrations of histamine, as measured with rhinostereometry, but there was no significant difference between the 2 groups in any of the variables. Serum soluble intercellular adhesion molecule-1 was not elevated in the pregnancy rhinitis group. CONCLUSIONS: This study found no increased frequency of allergy in general in women who have had pregnancy rhinitis. However, IgE against house dust mite was more frequent in the pregnancy rhinitis group. Smoking seems to be a risk factor, but age, parity, sex of the child, and hyperreactive nasal mucosa do not. Soluble intercellular adhesion molecule-1 was not elevated during pregnancy rhinitis.     

组胺H4受体及其拮抗剂对变应性鼻炎大鼠的作用研究

目的 通过变应性鼻炎(allergic rhinitis,AR)动物模型,观察组胺H4受体拮抗剂JNJ 7777120对AR大鼠的影响.方法 60只Wistar大鼠以随机数字表法分为5组,每组12只,分别为:正常对照(NC)组、AR模型未处理(AR)组、组胺H1受体拮抗剂氯雷他定处理(HR1)组、组胺H4受体拮抗剂JNJ 7777120处理(HR4)组及组胺H1、H4受体拮抗剂联合处理(HR1+4)组.以卵清蛋白建立大鼠AR模型,比较各组大鼠喷嚏、抓鼻次数、血清总IgE、白细胞介素(interleukin,IL)4、γ干扰素(interferon-γ,IFN-γ)以及及鼻腔灌洗液中趋化因子Eotaxin含量的差异.采用SPSS 13.0软件对数据进行分析.结果 各干预(HR1、HR4、HR1+4)组与AR组相比喷嚏、抓鼻次数、血清总IgE、IL-4、趋化因子Eotaxin含量均显著下降,而IFN-γ显著升高,差异有统计学意义(P值均0.05).HR4组大鼠平均((x)±s,下同)喷嚏、抓鼻次数、血清总IgE、IL-4分别为(29.3±6.5)次、(28.4±7.0)次、(147.67±28.79)mg/ml、(289.05±16.94)Pg/ml,较HR1组的(23.2±5.6)次、(21.4±5.2)次、(100.32±6.00)mg/ml、(267.71±24.26)Pg/ml升高,差异有统计学意义(q值分别为3.72、4.16、8.01、4.96,P值均<0.05),而INF-γ水平在HR4组为(28.17±1.97)pg/ml,低于HRI组的(35.45±1.35)pg/ml,差异有统计学意义(q=3.18,P<0.05).各干预组(HR1、HR4、HRI+4)中Eotaxin含量差异无统计学意义(P=0.096).结论 组胺H4受体拮抗剂JNJ 777120与组胺H1受体拮抗剂氯雷他定同样可以缓解AR症状及炎性反应状态,两者之间未发现有协同作用,JNJ 7777120与氯雷他定相比作用相对较弱.     

Toll样受体激动剂在变应性鼻炎免疫治疗中的研究进展

变应性鼻炎(AR)是由多种信号通路和细胞因子共同参与的鼻腔黏膜慢性炎症性疾病。Toll样受体(TLRs)作为一种重要模式识别受体(PRRs),介导细胞内信号转导通路,参与机体天然免疫和适应性免疫应答,在AR的发生、发展过程中发挥重要作用。近年来,TLRs作为治疗靶点在AR的治疗中取得良好疗效,TLRs激动剂可作为免疫制剂或免疫佐剂,在AR的免疫治疗中有广阔的应用前景。为进一步开发TLRs激动剂在临床上的可能价值,本文总结了TLRs激动剂在AR治疗中的研究进展。