《变应性鼻炎及其对哮喘的影响（ARIA）》变应原免疫治疗的医疗路径：要点解读

2019年2月《Allergy》杂志发表了《2019 ARIA变应原免疫治疗的医疗路径》。本意见书由Jean Bousquet为代表的欧洲变态反应与临床免疫学会百余名过敏学专家和单位组成的工作组共同执笔完成。该意见书运用循证学依据，提出了针对变应原免疫治疗（allergen immunotherapy，AIT）的综合医疗路径（integrated care pathways，ICPs）的新理念，旨在使AIT最大限度的发挥其对变应性疾病的作用。我们将该意见书与中国《变应性鼻炎诊断和治疗指南（2015年，天津）》、《EAACI变应性鼻结膜炎变应原免疫治疗指南(草案)要点解读》以及最新版的中国《变应性鼻炎变应原免疫治疗新指南》进行比较，借以解读。     

国际变应性鼻炎和哮喘的变应原特异性免疫治疗简明指南介绍

全球过敏反应和哮喘欧洲协作网(Global Allergy and Asthma European Network,GA2LEN)特别工作组,针对变应性鼻(结膜)炎和哮喘进行变应原特异性免疫治疗(allergenspecific immunotherapy,SIT)中最常见的问题,参考1998年发表的关于SIT的欧洲过敏反应和免疫学会(European Academy of Allergy and Immunology,EAACI)意见书、WHO意见书[1]、2001年和2008年两版变应性鼻炎及其对哮喘的影响(allergic rhinitis and its impacts on asthma,ARIA)指南等文件,经过2次讨论会达成了共识,随后该共识经过35位GA2LEN专家的审阅,于2010年正式发表,名为变应性鼻炎和哮喘的SIT简明指南(指南)[2].该指南所涉及的问题与临床实践密切相关,包括:患者选择、变应原产品、SIT的途径和治疗注意事项等.     

变应性鼻炎变应原免疫治疗新指南

正中国变应性鼻炎(allergic rhinitis,AR)的疾病负担近年来迅速加重,据报道全国17个城市人群的平均患病率已达17.6%,对患者的生活质量乃至家庭和社会经济造成严重影响。变应原免疫治疗(allergen immunotherapy,AIT)是目前唯一可以调节AR患者免疫系统的对因治疗措施,并可影响疾病的自然进程,预防新发致敏和减少AR发展为哮喘的风险。AIT的有效性、长效性和安全性已被众多临     

成年慢性鼻-鼻窦炎患者药物治疗依从性分析

慢性鼻-鼻窦炎是临床常见病及多发病。欧美学者相继组织制定了一系列有关鼻-鼻窦炎诊疗方面的指导性文件〔1-3〕。中华医学会耳鼻咽喉头颈外科学会鼻科学组发布了《慢性鼻-鼻窦炎诊断和治疗指南(2008年,南昌)》(以下简称《指南》),旨在     

舌下免疫治疗的临床现状及问题

<正>变应原免疫治疗(allergen immunotherapy)是一个针对明确的变应原导致IgE介导的Ⅰ型变态反应疾病的对因治疗方法,临床上也称为脱敏疗法(desensitization),目的是为了提高机体对致敏变应原的耐受性。根据中华医学会最新版变应性鼻炎(allergic rhinitis,AR)诊疗指南~[1],变应原免疫治疗应该作为AR的一线治疗方案,除了对疾病本身有治疗     

变应原特异性免疫治疗的禁忌证

变应原特异性免疫治疗(specific immunotherapy,SIT)被认为是一种有可能从根本上调节变态反应发病机制的"对因疗法",是目前治疗变应性鼻炎(AR)的重要手段之一.SIT包括皮下免疫治疗(subcutaneous immunotherapy,SCIT)和舌下免疫治疗(sublingual immunotherapy,SLIT).SCIT可针对吸入性变应原和蜂毒变应原,而SLIT只针对吸入性变应原[1].迄今为止,SIT的适应证较明确,疗效亦已被证实,但这并非意味着每一位符合适应证条件的患者均可进行SIT,在SIT开始前掌握其危险冈素、评估风险-获益比是非常必要的.遗憾的是,SIT的禁忌证目前仍处在争论之中,且在各权威指南中仅多为"提及"而未详细解释原因.     

重视季节性变应性鼻炎的预防性治疗

变应性鼻炎(AR)是临床常见多发疾病,近年来患病率显著上升,已成为全球性公共卫生问题,引起广泛关注,国内外相继出台了多个版本的临床指南[1-6].AR的治疗原则和策略是防治相结合,包括环境控制(避免接触变应原和刺激物)、药物治疗、特异性免疫治疗,以及加强患者教育,提高对疾病的认识,提高治疗依从性[7].2010年版"变应性鼻炎及其对哮喘的影响(Allergic Rhinitis and its Impact on Asthma,ARIA)"指南采用新的循证医学评价体系——推荐分级的评估、制订与评价(grading of recommendations assessment,development and evaluation,GRADE),重视临床试验的证据质量,提出了各项干预措施的推荐强度[4],这对提高AR防治水平无疑具有重要价值,但不容忽视的是,在临床实践中还存在诸多问题值得进一步探讨.     

气传变应原皮肤点刺试验临床操作指南

皮肤点刺试验(skin prick test,SPT)是诊断患者是否过敏的首要方法,临床应用广泛,但一直缺乏统一的检测工具和结果评估标准.2012年Bousquet等46位全球变态反应(过敏)和哮喘欧洲协作组织(global allergy and asthma European network,GA2LEN)和变应性(过敏)鼻炎及其对哮喘的影响(allergic rhinitis and its impact on asthma,ARIA)的成员,在1993年欧洲过敏科学协会的相关文件,以及2001年和2008年两版ARIA相关数据的基础上,综合分析了64篇参考文献,达成了关于气传变应原SPT临床操作指南共识,经GA2LEN成员讨论通过,在Allergy以指南的形式发表[1].     

编辑导读

本期重点号内容是"变应性鼻炎(AR)免疫治疗(AIT)"。述评《过敏原特异性免疫治疗——现状与未来》通过AIT的作用机制、患者选择、不同治疗方案的介绍等, 对AIT的研究现状与未来发展进行了论述。论著《标准化螨过敏原提取物皮下冲击免疫治疗的短期疗效和安全性观察及相关因素探讨》比较了3种不同剂量递增模式的AIT的早期的临床疗效、不良反应、炎性因子的变化, 以期为临床更加安全有效地开展加速AIT提供参考。《变应性鼻炎皮下过敏原特异性免疫治疗过长延迟注射的剂量调整新方案疗效分析》探究了AR尘螨皮下免疫治疗(SCIT)维持期中断治疗超过16周的新型剂量调整方案的有效性及安全性, 发现相较于指南推荐剂量调整方案, 新方案的有效性及安全性无显著差异。《成人变应性鼻炎经颈部淋巴结内免疫治疗远期疗效的随机对照研究》通过与SCIT对比, 观察了经颈部淋巴结内免疫治疗(ICLIT)对于成人AR的远期疗效及安全性, 指出ICLIT是今后AR AIT的一种新型的补充选择。《标准化尘螨过敏原SCIT对儿童AR患者治疗期间的疗效及安全性分析》提出标准化尘螨SCIT具有良好的安全性, 治疗期间对不同临床特征的儿童A...     

沈阳市中学生变应性鼻炎的变应原分布特点

目的分析沈阳市中学生变应性鼻炎(AR)的变应原分布特点,提出对本地区青少年AR有针对性的防治策略。方法按照2006年WHO发布的《变应性鼻炎及其对哮喘的影响》(allergic rhinitis and its impacton asthma,ARIA)指南,对沈阳市2000名14～16岁中学生进行问卷调查,确定182名中学生患有AR。行皮肤点刺试验,分析其变应原,并对患者的鼻部症状行视觉模拟量表(visual analogue scale,VAS)评分和鼻结膜炎相关生活质量问卷(rhinoconjunctivitis quality of lifequestionnaire,RQLQ)进行相关性分析。结果 182例患者中,未检测出变应原者54例,检出1种变应原者15例(11.72%),检出2种变应原者19例(14.84%),检出3种及以上变应原者94例(73.44%)。屋尘螨为最常见变应原,共检出106例。鼻部症状的严重程度和生活质量呈正相关(r=0.653,P<0.001)。结论尘螨是沈阳中学生AR的主要变应原。     

One‐stop neck lump clinic: phase 2 of audit. How are we doing?

One‐stop neck lump clinic: phase 2 of audit. How are we doing? Regular monitoring and audit of a service are integral to ensuring maintenance of efficiency and standards. This is particularly important where the quality of the service is operator dependent, as is the case in the clinical diagnosis of neck lumps and fine needle aspiration cytology. The one‐stop neck lump clinic has now been running in the department for more than 20 months. A previous article described the results of the first phase audit carried out at 6 months and had identified a waiting time to be seen that was longer than that recommended by the British Association of Otorhinolaryngologists, Head and Neck Surgeons. Measures were implemented to reduce this waiting time and a second audit was carried out after another 10 months with the aims of assessing if modification of the means of referral reduces waiting time and if the outcomes of clinical performance in phase 1 could be maintained or improved. We discuss the results of phase 2 in the audit spiral.     

A Decrease in Maxillary Sinus Pressure,as Seen in Upper Airway Allergy or Infection,Results in an Increase in Upper Airway Nitric Oxide Levels

The paranasal sinuses are connected to the nasal cavity via small osties. Ostial occlusion, caused by mucosal swelling, will result in a slowly increasing negative pressure inside the sinus cavity. In parallel, the oxygen content in the sinus will decrease, resulting in the development of relative hypoxia. Hypoxia is a powerful inducer of nitric oxide (NO) synthase, and inducible NO synthase has been shown to be present in considerable amounts in the upper airways, including the sinuses. The present study was designed to investigate whether a reduction in sinus pressure would affect upper airway NO production. Thirteen healthy volunteers were investigated. A pressure chamber was used to lower the ambient pressure to-4.9 kPa. NO was sampled from one nostril or via a drainage tube inserted into the maxillary sinus before, during and after the hypobaric exposure. When the pressure was decreased, NO levels increased from 256 &#45 15 to 316 &#45 19 ppb ( n =13, p <0.001). The NO levels remained elevated (282 &#45 21 ppb; p <0.05) when measurements were repeated 20 min after leaving the chamber. The nasal airway resistance (V2 tot ) also increased as a result of the chamber session (from 16 &#45 2° before to 21 &#45 3° after; p <0.05). An increase in NO levels was also found when the experiments were repeated with NO sampled directly from the maxillary sinus (225 &#45 6 before and 265 &#45 9 ppb after; n =6, p <0.001). For control purposes the nasal analyses were repeated again, this time under hyperbaric conditions (+4.9 kPa). This resulted in a slight decrease in the NO levels (from 273 &#45 22 to 241 &#45 17 ppb; n =10, p <0.001), but there was no change in the nasal airway resistance. We conclude that a reduction in sinus pressure, as seen in upper airway allergy or infection, may result in an increase in upper airway NO production.     

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF‐C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty‐two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow‐up was 2 years after radiotherapy. Expression of VEGF and VEGF‐C was evaluated by immunohistochemistry of formalin‐fixed, paraffin‐embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF‐C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF‐C (P < 0.001). In addition, the expression of VEGF‐C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF‐C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF‐C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.     

Treatment of Maxillary Sinus Carcinoma: Clinical Results Using the Kitasato Modality

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.0% for Stage IVB.     

Cervical Reflex Induced by Click Stimuli in Cats

We studied click-evoked potentials in the anterior horn of the spinal cord in 17 cats. A concentric needle electrode was inserted into the anterior horn of the spinal cord at levels C3-C6. Potentials evoked with 105 dB SPL clicks were recorded with a peak latency of 4.89-5.10 ms only at the C3 level. These responses were observed 45-60 dB SPL above the auditory brainstem response (ABR) threshold, and no potentials were evoked by stimulation of the contralateral ear. Average was performed 100 times with changes in stimulation frequency of 1-20 Hz. The amplitude of the potentials decreased with increasing stimulus frequency, but there were no changes in ABRs. The responses disappeared after destruction of the medial vestibulospinal tract at the obex level, but ABRs were still recorded. The spinal nucleus of the accessory nerves was located in the anterior horn of the spinal cord at levels C1-C6, and the sternocleidomastoid muscle motoneurons were found at levels C1-C3. The click-evoked potentials recorded in this study reflect responses of the spinal nucleus of accessory nerves through the vestibulospinal tract to click stimulation. The responses have the same characteristics as vestibular-evoked myogenic potentials that can be recorded using surface electrodes over the sternocleidomastoid muscles of humans.     

Tongue Base Reduction with Temperature-controlled Radiofrequency Volumetric Tissue Reduction for Treatment of Obstructive Sleep Apnea Syndrome

In recent years a considerable effort has been made to establish the use of different surgical techniques for the treatment of obstructive sleep apnea syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to tongue base hypertrophy remains in many ways an unsolved problem. The aim of this study was to evaluate the safety and efficacy of tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction in the treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were treated with radiofrequency tissue ablation. An intensified treatment protocol was used, delivering 2,800 J per treatment session under local anesthesia. Two nights of polysomnography testing were performed before and after treatment. Daytime sleepiness, snoring and postoperative morbidity were assessed using questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to 24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured after the procedure (reduction in RDI of &#83 50% and a postoperative RDI of <15/h) and ten (55%) showed an improvement of >20% in their RDI. Daytime sleepiness and snoring improved significantly. Peri- and postoperative morbidity was low; one severe complication occurred (tongue base abscess). We were able to achieve similar cure and responder rates to those reported in a recently published pilot study but with a reduced number of treatment sessions. We believe that this technique may improve patient acceptance and have beneficial cost implications.     

A simple objective evaluation and grading for facial paralysis outcomes

Matrix metalloproteinase (MMP)-2 and -9 degrade type IV collagen, which is one of the major components of the basement membrane in normal tissue and expressed in the surroundings of the cancer nest in squamous cell carinoma. The degeneration of type IV collagen is an essential step in the metastasis to lymph nodes and distant organs. In this study, we examined MMP-2 and -9 levels of cancer tissue and serum obtained from patients with head and neck squamous cell carcinoma (HNSCC) in order to evaluate the relationship between the clinicopathologic features and MMPs. We examined the production of MMP-2 and -9 in cancer tissue homogenates of 73 patients who had HNSCC and the serum MMP levels of 16 patients with HNSCC and 8 healthy volunteers. We also studied the localization of MMP-2 in the carcinoma using an immunohistochemical approach. The concentrations of MMP-2 and -9 in the tissue homogenates and serum were measured by means of a sandwich enzyme immunoassay using a monoclonal antibody. Immunohistochemical analyses were performed with monoclonal antibody to MMP-2. The concentration of MMP-2 in the tumor tissue homogenates was unrelated to tumor size, but that in patients with lymph node metastases was significantly higher than in those without lymph node metastases. The concentration of MMP-9 was unrelated to lymph node metastasis and tumor size. The levels of both MMP-2 and -9 in serum were unrelated to lymph node metastasis. Immunohistochemistry indicated that MMP-2 was mainly expressed in cancer cells. Because MMP-2 degrades type IV collagen, the level of MMP-2 in carcinomas may be a useful indicator of the degree of invasion and metastasis.     

A case of cortical deafness and anarthria

The nasal epithelium protects the underlying tissue from damage. Epithelial cell growth is controlled by epidermal growth factor (EGF) and is possibly affected by toxic proteins, e.g. eosinophil cationic protein (ECP). The aims of this study were to examine nasal fluid epithelial cell counts and their relations to EGF, eosinophils and ECP in 23 patients with seasonal allergic rhinitis and 20 healthy controls. Nasal fluid epithelial cell counts were lower in patients than in controls. EGF levels did not differ between patients and controls, and correlated with epithelial cell counts in controls but not in patients. Eosinophils and ECP were higher in patients than in controls, but did not correlate with epithelial cell counts. The role of growth factors, such as EGF, in regulating epithelial cells merits further study.     

Lack of significant estrogen and progesterone receptor expression in nasal telangiectasias in hereditary hemorrhagic telangiectasia: an immunohistochemical analysis

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change - 39, SD 57.3, p <0.001), recall (mean change - 24.3, SD 39.3, p <0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change-9.1, SD 15.7, p <0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p <0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p <0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.