变态反应性支气管肺曲菌病的治疗:需要更多的循证依据

变态反应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)是一个被临床忽视的疾病,常被误诊为哮喘和肺结核等疾病。有关ABPA自然病程和治疗的临床研究还比较缺乏,以往多以口服糖皮质激素治疗为主,目前普遍推荐口服糖皮质激素加抗真菌治疗的联合治疗方案,以达到控制机体对烟曲菌抗原的过敏反应、同时清除寄生于气道内的烟曲菌等。     

缓激肽在过敏性疾病发病机制中的作用

作为激肽释放酶-激肽系统的终末效应物质之一,缓激肽具有多种生物活性,如扩血管、增加血管通透性、诱导非血管平滑肌收缩等。近年来围绕缓激肽在过敏性哮喘、鼻炎等过敏性疾病中的作用开展了一些新的研究,并取得了一些进展。本文从激肽释放酶-激肽系统,缓激肽受体及受体后信号转导,缓激肽与过敏性疾病、血管性水肿的关系及以缓激肽为靶点的抗过敏药物研发等方面综述了缓激肽在过敏性疾病发病机制中的作用。     

雷暴哮喘

在过去的30余年,全球范围内关于雷暴相关严重哮喘发作事件的报道逐年增加,主要集中于澳大利亚、英国。这种因天气因素导致的哮喘发作或加重多发生于花粉季节,认为与花粉或霉菌过敏有关。雷暴哮喘发生机制可能是花粉颗粒在雷暴天气时溶胀、崩解释放大量具有变应原性的碎片,使空气中变应原浓度短时间内明显升高,气道高反应个体暴露后出现哮喘症状。花粉或霉菌导致的过敏性鼻炎、哮喘患者是雷暴哮喘的高危人群。了解雷暴哮喘有助于对其预防,并降低其对患者生命健康及公共卫生服务的危害。     

sICAM-1 and TNF-α in Asthma and Rhinitis: Relationship with the Presence of Atopy

Background. A genetically determined overproduction of specific immunoglobulin E (IgE) underlies many diseases like asthma or allergic rhinitis. IgE as well as tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) play a critical role in the induction and maintenance of inflammation. While the correlation between IgE and atopy is inseparable, little is known about the correlation of atopy with markers of inflammation. Objective. We investigated the relationship between the serum concentrations of TNF-α, soluble ICAM-1 (sICAM-1), and the presence of atopy in patients with persistent rhinitis or asthma. Methods. Serum concentrations of sICAM-1, TNF-α, and total IgE were investigated in 64 adults with persistent allergic rhinitis, 17 subjects with nonatopic rhinitis, 90 patients with asthma, and 21 healthy individuals. Atopy was diagnosed on the basis of positive family history, skin prick tests, and serum IgE concentration. Results. Total IgE concentration was significantly higher in patients with atopic rhinitis or asthma when compared with nonatopic patients and healthy individuals and was the highest in patients suffering from severe atopic asthma who were not treated with systemic glucocorticosteroids. Although there were marked alterations in IgE in atopic and nonatopic patients, there were no significant differences between atopic and corresponding groups of nonatopic rhinitic and asthmatic patients in sICAM-1 and TNF-α concentrations. (sICAM-1 in rhinitis: atopic vs. nonatopic patients: 224.02 and 221.08 ng/ml, respectively, p > .05; in mild/moderate asthma: atopic vs. nonatopic: 306.22 and 326.39 ng/ml, respectively, p > .05; severe asthma without oral corticosteroids therapy: atopic vs. nonatopic: 418.03 and 468.09 ng/ml, respectively, p > .05; and severe asthma with oral corticosteroids therapy: atopic vs. nonatopic: 320.66 and 308.09 ng/ml, respectively, p > .05). Conclusions. Concentrations of sICAM-1 and TNF-α are significantly higher in patients with asthma compared with those observed in patients with rhinitis, but they are independent of the presence of atopy.     

阿罗格变应原皮肤点刺试验在变应性疾病诊断中的临床意义

目的　探讨阿罗格变应原皮肤点刺试验在变应性疾病诊断中的临床价值。方法　用 2 0种德国默克公司阿罗格变应原进行皮肤点刺试验 ,以生理盐水为阴性对照 ,组胺为阳性对照。结果　临床拟诊为变应性疾病的2 0 0 0例患者中 ,粉尘螨、屋尘螨的阳性率分别为 4 1.4 0 %和 4 0 .6 0 % ,其他 18种变应原的阳性率为 0 .4～ 2 8.6 % ,阳性对照的阳性率为 6 %。变应性鼻炎组粉尘螨和屋尘螨分别为 73.2 0 %和 71.36 % ,狗上皮为 33.5 4 % ;哮喘组粉尘螨和屋尘螨为 5 1.4 %和 4 9.4 4 % ,食物组以咖哩和小虾多见。选择螨类及其他变应原阳性的患者 5 0例行脱敏治疗 ,4 8例显效 ,疗效满意。结论　阿罗格变应原皮肤点刺试验为变应性疾病的诊断提供有力的依据 ,为特异性脱敏治疗提供可靠的客观指标。具有方便安全、操作简单、假阳性少、多种变应原可同时检测、特异性高等优点。     

Case Report: Allergic Bronchopulmonary Aspergillosis and Allergic Fungal Sinusitis Successfully Treated with Voriconazole

Allergic bronchopulmonary aspergillosis and allergic fungal sinusitis are closely related disorders that rarely present in the same individual. The mainstay of treatment for allergic bronchopulmonary aspergillosis is systemic corticosteroids. Itraconazole is used as adjunctive therapy in refractory cases. Allergic fungal sinusitis requires initial sinus surgery followed by systemic steroids. Antifungal therapy has not proven to be beneficial in allergic fungal sinusitis. We report a case of concomitant allergic bronchopulmonary aspergillosis and allergic fungal sinusitis that was refractory to standard therapy but had dramatic clinical response following treatment with voriconazole.     

体内植入物过敏：先进科技的双刃剑？——从变态反应视角看植入物不良反应

各种体内植人物均可引起人体超敏反应,除影响局部组织外,常波及远隔部位的皮肤和黏膜。本文结合1例节育环中铜过敏导致掌跖脓疱病和2例口腔植入物过敏导致局部皮肤黏膜病变,就宫内节育器、口腔和骨科假体、心血管内装置、人工耳蜗和硅胶过敏进行分析讨论。     

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变应性鼻炎(AR)与支气管哮喘均是上、下气道的一种慢性炎症性疾病,在流行病学、病理生理学和治疗方法上存在相似性和相关性,在临床上被称为"同一气道,同一疾病"。AR增加支气管哮喘患者的症状和就诊的需求,不利于支气管哮喘控制,AR对支气管哮喘的影响(ARIA)推荐对AR和支气管哮喘要进行联合诊断并同时治疗。     

肺部阴性的结核性变态反应综合征87例

目的探讨肺部阴性的结核性变态反应综合征的病因、发病机制、临床表现、诊断、误诊情况、治疗及预后。方法汇总分析在我院住院期间87例诊断为结核性变态反应综合征且无肺结核病灶的患者的临床资料。结果 47.13%的患者有不同程度发热,44.83%的患者出现多发性关节炎,59.77%的患者有皮肤损害,4.60%的患者出现心肌受累,73.56%的患者血沉增快,12.64%的患者出现抗"O"升高,结核菌素皮试强阳性反应90.8%,血清抗结核抗体检查71.26%阳性;临床误诊率81.61%;规则抗结核治疗率100%。结论肺部阴性的结核性变态反应综合征临床误诊率较高,结核杆菌感染所致变态反应是该综合征的始动因素,临床上以发热、皮肤结节性红斑及游走性的关节疼痛等为主要表现,血清抗结核抗体检查及结核菌素皮试有较高的诊断价值。     

A case of allergic bronchopulmonary aspergillosis following active pulmonary tuberculosis

Allergic bronchopulmonary aspergillosis usually occurs in children with underlying airway disease such as asthma and cystic fibrosis. While the colonization and infection of pre‐existing tuberculosis lesions by aspergillus species is well known, occurrence of allergic bronchopulmonary aspergillosis following pulmonary tuberculosis in children has not been reported yet. Here, an 11‐year‐old girl who developed allergic bronchopulmonary aspergillosis following active pulmonary tuberculosis is reported and the mechanisms of causality are also speculated. Pediatr Pulmonol. 2009; 44:86–89. © 2008 Wiley‐Liss, Inc.     

Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response

Background and Aims: Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high‐dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. Methods: Fifteen birch pollen‐allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. Results: Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood–eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 × 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 × 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). Conclusions: Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis. Please cite this paper as: Kämpe M, Janson C, Stålenheim G, Stolt I and Carlson M. Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response. The Clinical Respiratory Journal 2009; DOI:10.1111/j.1752‐699X.2009.00140.x.     

Clinical Manifestations of Allergic Bronchopulmonary Aspergillosis without Major Features of Asthma Diagnosed by the New Criteria in Japan

Allergic bronchopulmonary aspergillosis (ABPA) is a severe form of asthma in which structural airway destruction occurs due to a hypersensitivity reaction to fungi. A 25-year-old man without any major features of asthma had lung infiltration with dilatation of the central bronchus, high-attenuation mucus with histological eosinophilic invasion, fungi detected on cultures, and positive Aspergillus-specific immunoglobulin E (IgE) and precipitating antibody of Aspergillus, with a significant elevation of blood eosinophils and slightly increased total IgE. He recovered rapidly with systemic corticosteroid therapy without recurrence over 1-year follow-up and an increased forced expiratory volume in one second, which supported the possibility of ABPA without any major features of asthma.     

Seasonal Changes in Platelet Activity in Pollen-Induced Seasonal Allergic Rhinitis and Asthma

Background. Previously we reported that patients sensitized to pollen-allergens who had seasonal allergic rhinitis and seasonal asthma may show increased plasma levels of platelet activation markers during grass pollen season. Objective. To find out whether the pattern of platelet activity measured by plasma PF-4 level in the same group of patients changed off-season compared with the pollen season as well as in comparison with healthy control subjects. Methods. Off-pollen season, plasma PF-4 level was determined by enzyme-linked immunosorbent assay (ELISA) in 16 grass pollen allergic patients who had seasonal allergic rhinitis and seasonal asthmatic symptoms (none of them had any history of allergic diseases outside the season) and in 29 healthy nonatopic subjects. Results. Plasma PF-4 level in the patients off–pollen season was significantly lower as compared with the season and did not differ significantly as compared to the healthy subjects. Conclusions. This observation taken along with our previous results indicates that patients with seasonal allergic rhinitis and asthma symptoms may have an increased circulating platelet activation, yet this phenomenon disappears in the asymptomatic period of the disease. This might indicate that platelet activation within the systemic circulation is an important factor in the development of seasonal allergic airway inflammation.     

大容量人免疫球蛋白G基因文库的构建及初步应用

目的从大容量人免疫球蛋白G基因文库中获得尘螨2类变应原特异的IgG Fab片段。方法通过DNA重组技术,从300名健康志愿者的外周血淋巴细胞中扩增全套人抗体轻链及重链Fd基因,分别插入pFab1-His2相应位置,构建人免疫球蛋白G基因文库;以重组粉尘螨2类变应原（rDer f2）作为抗原,采用克隆印迹法对抗体库进行筛选,ELISA验证以获得阳性克隆;提取阳性克隆质粒,进行核苷酸序列测定并推算氨基酸序列,Kabat数据库分析轻、重链基因的同源性,表面等离子共振BIAcore检测纯化的Fab片段与rDer f2的亲和力。结果从9×10^8库容的人免疫球蛋白G基因文库中筛选1.28×10^6个克隆,获得2个可与尘螨变应原特异结合的阳性克隆AM1和AM2。序列比较显示2个克隆的重链完全同源;同源性分析显示,AM1、AM2轻链可变区近似系分别为K2-30和K1-12,重链可变区近似系为VH3-30;BIAcore检测显示,2个克隆的Fab片段与rDer f2的结合常数分别为6.1×10^7和5.7×10^7,解离常数分别为3.1×10^-8和4.1×10^-8。结论从未经免疫的大容量人免疫球蛋白G基因文库获得具有较高亲和力的尘螨变应原特异的IgG Fab片段。     

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特异性免疫治疗(SIT)是变态反应疾病特有的病因治疗方法,是除避免接触变应原外能够影响变态反应疾病自然进程的惟一治疗手段。针对目前SIT特别是皮下注射免疫治疗(SCIT)存在的问题,国内外变态反应学者进行了大量研究,文章对SIT新的给药途径、新的适应证、变应原提取液制剂的改进、合并应用Anti-IgE治疗及cDNA免疫治疗等方面的研究进展进行了简要综述并对其临床应用前景进行了展望。     

Acute hemodynamic and coronary circulatory effects of experimental autoimmune myocarditis

Summary Myocarditis and progression to cardiomyopathy is associated with focal spasm and reperfusion of the coronary microcirculation. Experimental autoimmune myocarditis (EAM), induced with cardiomyosin peptide-specific T cells in Lewis rats, was hypothesized to cause acute hemodynamic and coronary vasculature changes. Fifteen experimental animals (5 each at 1, 2, and 3 weeks after T-cell injection) and eight controls were studied using the constant pressure variant of the isolated heart. Coronary resistance decreased while coronary flow increased (P < 0.05) in EAM hearts after the first week. Rate-pressure product, +dP/dt and –dP/dt, decreased while the heart/body weight ratio increased (P < 0.05) compared with controls at 1 week but not at 2 or 3 weeks. Mean local myocardialPO₂, which reflects local oxygen delivery and consumption, and MVO₂ were not different for EAM hearts. However, compared with controls EAM myocardialPO₂ varied more widely and was often beyond the usual range, suggesting the occurrence of localized hypoxic and hyperoxic areas. In summary, after the first week there was a significant decrease in coronary resistance in the EAM animals, which required higher flow to maintain a similar perfusion pressure. These changes in coronary resistance and flow along with the heterogeneity and extremes of local myocardialPO₂ levels without a significant change in MVO₂ may be explained by postulating development of low-resistance, high-flow hyperoxic areas which steal flow, thus causing hypoxia in other areas.This work was supported by AHA, New Hampshire Affiliate Grant-in-Aid 9407770S, and NIH Grant Program Project GM 51630, and made use of the EPR Center at Dartmouth Medical School which was supported by NIH Grant RR 11602.     

支气管哮喘患者合并变应性鼻炎的临床调查

目的调查支气管哮喘患者中变应性鼻炎的发生率,并对其临床诊治现状作初步分析。方法连续调查98例确诊的哮喘患者,详细了解其临床表现及诊治现状,并对所得数据进行统计学分析。结果 98例哮喘患者中63例（64.3%）并发变应性鼻炎,其中54例（85.7%）被误认为系反复感冒者。哮喘合并变应性鼻炎组（63例）和单纯哮喘组（35例）在年龄、病程等方面差异无显著性（P〉0.05）。仅在9例变应性鼻炎患者中有6例间断使用过鼻喷皮质类固醇激素治疗。结论较多的哮喘患者合并变应性鼻炎,及反复误诊提示应关注哮喘合并变应性鼻炎的诊治。当前对哮喘合并变应性鼻炎的诊治关注不足。