免疫组化法检测致死性哮喘死亡患者肺部嗜碱粒细胞

嗜碱粒细胞表达高水平、高亲和力的ＩｇＥ受体 ,也是全身过敏反应的效应细胞 ;刺激嗜碱粒细胞可以释放组胺和其它预先形成的介质 ,合成另外的介质和细胞因子。嗜碱粒细胞在支气管哮喘中的作用尚难以确定。作者使用已被确认的一种嗜碱粒细胞特异性抗原识别单克隆抗体 2Ｄ7,免疫组化法定量检测致死性哮喘(ＦＡ)死亡患者肺部嗜碱粒细胞 ,对比ＦＡ死亡患者与非哮喘死亡患者的差异。方法　分别取 3组尸检肺标本。①ＦＡ组 :患者 5例 ,年龄 1 4～ 44、平均 3 1岁 ;②非致死性哮喘组 (ＮＦＡ)有哮喘病史的患者 6例 ,年龄 3 8～ 80 (平均 50 )岁 ;③…     

支气管哮喘小气道炎症及结构变化

通过对哮喘患者的尸检和活体组织检查,发现哮喘患者的气道有炎症浸润和结构改变。但在这些研究中都注意的是大气道的变化。哮喘患者小气道的病理变化是否与大气道相同,炎症反应是否导致小气道的结构改变。是人们极为关注的问题。 炎症细胞:研究观察了大、小气道的炎症细胞数量,通常把直径小于2mm的气道定义为小气道。Synek等对死于哮喘的患者,与患有哮喘但死于其他原因的患者的气道上皮及支气管壁中的白细胞数量进行了比较。结果表明,嗜酸粒细胞在支气管上皮的浸润遍及大小气道。急性重症哮喘患者近端气道浸润严重。在一组死于急性、窒息性哮喘的5例患者中有同样发现。其T细胞、嗜酸粒细胞和巨噬细胞的数量在近端气道高于直径小于1mm的气道。对切除的肺组织     

神经生长因子对哮喘大鼠气道炎症中TNF-α表达的调节作用

目的 探讨神经生长因子(NGF)在哮喘发病中对气道炎症TNF-α mRNA表达的调节作用.方法 实验分为对照组、哮喘组、NGF阻断组.免疫组化方法结合显微图像分析检测NGF的表达,以及抗NGF干预后哮喘的发作情况、嗜酸性粒细胞及TNF-α mRNA表达的关系.结果 NGF阻断组与哮喘组比较,哮喘发作次数、嗜酸性粒细胞计数显著减少(均P＜0.01),肺组织炎症表现显著减轻.哮喘组大鼠肺组织内NGF mRNA表达水平较对照组显著增高(P＜0.05),NGF阻断组肺组织内TNF蛋白及TNF-a mRNA的表达较哮喘组明显减少(P＜0.05).结论 NGF阻断可减少肺部嗜酸粒细胞浸润、哮喘的发作次数及TNF-α mRNA蛋白的表达,并可以抑制气道炎症.     

嗜酸性粒细胞、气道上皮细胞、糖皮质激素与支气管哮喘的研究进展

嗜酸性粒细胞是支气管哮喘发病机制中的主要效应细胞,与哮喘病情的严重性密切相关.聚集、浸润入气道和肺组织的嗜酸性粒细胞在发生凋亡及凋亡后被巨噬细胞和气道上皮细胞吞噬,对哮喘炎症的消退具有重要意义.糖皮质激素可促进嗜酸性粒细胞凋亡及凋亡后的被吞噬.本文就嗜酸性粒细胞、气道上皮细胞、糖皮质激素与支气管哮喘的研究进展作一综述.     

Significance of serum eosinophil cationic protein and interleukin-4 and their significance in bronchial asthma

目的 探讨支气管哮喘患者血清嗜酸性粒细胞阳离子蛋白(ECP)和白细胞介素(IL)-4的变化及其临床意义.方法 收集哮喘患者54例,并将其分为哮喘缓解组(26例)和哮喘发作组(28例),血清嗜酸性粒细胞阳离子蛋白和IL-4水平的检测应用酶联免疫吸附法(ELISA).结果 与对照组相比较,哮喘急性发作期嗜酸性粒细胞阳离子蛋白、IL-4含量明显升高,FEV1显著下降(P＜0.05);治疗后嗜酸性粒细胞阳离子蛋白、IL-4水平均明显降低,FEV1、FEV1/FVC均升高.哮喘缓解期患者嗜酸性粒细胞阳离子蛋白、IL-4水平明显高于对照组.直线相关分析显示,嗜酸性粒细胞阳离子蛋白与IL-4呈正相关,与FEV1和FEV1/FVC呈负相关.结论 嗜酸性粒细胞阳离子蛋白和IL-4可作为评价哮喘患者气道炎症程度和指导抗炎治疗的指标.     

嗜酸性粒纽胞、气道上皮细胞、糖皮质激素与支气管哮喘的研究进展

嗜酸性粒细胞是支气管哮喘发病机制中的主要效应细胞，与哮喘病情的严重性密切相关。聚集、浸润入气道和肺组织的嗜酸性粒细胞在发生凋亡及凋亡后被巨噬细胞和气道上皮细胞吞噬，对哮喘炎症的消退具有重要意义。糖皮质激素可促进嗜酸性粒细胞凋亡及凋亡后的被吞噬。本文就嗜酸性粒细胞、气道上皮细胞、糖皮质激素与支气管哮喘的研究进展作一综述。     

20例嗜酸性粒细胞性胃肠炎临床及内镜特点分析

目的 探讨嗜酸性粒细胞性胃肠炎(EG)患者的临床表现及内镜检查对该病的诊治价值.方法 对20例EG患者的临床特点、试验室检查、内镜表现和治疗随诊情况进行分析.结果 20例患者中黏膜型12例、浆膜型2例、混合型6例;EG临床表现以腹痛为主,可伴有腹胀、腹泻、腹水、恶心、呕吐;外周血和骨髓中嗜酸性粒细胞计数明显增多(13.5%～50.6%和7.8%～38.5%).腹水中可见大量嗜酸性粒细胞;内镜表现为黏膜充血水肿、糜烂,病理检查可见大量嗜酸性粒细胞浸润;糖皮质激素治疗1～2周内可迅速缓解症状,减量维持,然后逐渐减量至停药;病情可反复,但预后良好.结论 EG患者临床和内镜表现无特异性,外周血和腹水中嗜酸性粒细胞计数明显增多,胃肠黏膜组织中嗜酸性粒细胞浸润是诊断的关键,糖皮质激素治疗效果良好.     

嗜碱粒细胞在过敏反应中的作用

嗜碱粒细胞占外周血白细胞的小部分（〈1％），鉴于这类细胞与肥大细胞相似，如表达高亲和力的IgE受体和释放组胺引起支气管收缩、支气管血流量增加、血管通透性增加、促进黏液分泌，以及作为嗜酸粒细胞趋化剂等，故嗜碱粒细胞被认为是“循环着的肥大细胞”。近研究发现，嗜碱粒细胞可释放大量的白三烯C4（LTC4）及LTB4致支气管强烈收缩。嗜碱粒细胞表面表达CD40L、CCR3和CD63，释放大量的Th2型细胞因子——IL-4和IL-13，对过敏反应的起始和持续起关键作用。目前认为肺组织内大量的嗜碱粒细胞通过多种途径参与了致死性哮喘的发病。对致死性哮喘患者肺组织进行免疫组化分析显示，肺组织内包括大小气道腔内、气道上皮、黏膜下层及肺泡有大量嗜碱粒细胞浸润，远远高于一般哮喘患者及正常对照组，提示嗜碱粒细胞可能参与了哮喘的炎症反应过程。由此激发了人们的思索：嗜碱粒细胞除了是IgE介导反应中的效应细胞外，还具有超乎想象的作用。以下从基础研究及临床实践简要阐述对人嗜碱粒细胞在过敏反应中地位的新认识。     

嗜酸性粒细胞性胃肠炎临床特点分析

目的 探讨嗜酸性粒细胞性胃肠炎（EG）的临床特征.方法 对21例EG患者的临床资料进行回顾性分析.结果 21例EG患者中,最常见的临床症状为腹痛（76.2％）,以及恶心呕吐、腹胀、腹泻、纳差等.20例外周血嗜酸性粒细胞增高（95.2％）,内镜检查见炎症最常累及胃窦及十二指肠球部,组织活检可见嗜酸性粒细胞浸润.黏膜型13例,混合型（黏膜型合并浆膜型）8例.腹腔积液阳性者（7例）,混合型所占比例、合并电解质紊乱例数及CRP水平均高于腹腔积液阴性者（14例）.21例确诊后均予饮食调节和去除过敏原治疗,同时给予抑酸、保护胃黏膜、调节胃肠动力和肠道菌群等药物,其中15例予泼尼松治疗.治疗后患者嗜酸性粒细胞计数低于治疗前,症状得到改善.结论 EG临床表现无特异性,超敏反应病史、外周血嗜酸性粒细胞计数增高、胃肠道组织嗜酸性粒细胞浸润有助于诊断,确诊依靠组织活检.合并腹腔积液者较无腹腔积液者病情重.治疗主要是去除过敏原及对症治疗,对于症状较重者可加用糖皮质激素.     

嗜酸性粒细胞性胃肠炎98例临床特点与诊治

目的探讨嗜酸性粒细胞性胃肠炎(eosinophilic gastroenteritis,EG)的临床特点,提高对疾病的认识,降低误诊率及漏诊率.方法回顾性分析郑州大学第一附属医院2011-06/2017-05确诊的98例EG患者的临床表现、实验室检查、内镜检查、治疗与预后等.结果 EG主要临床表现为腹痛(85/98),以黏膜型(82/98)常见;外周血及骨髓嗜酸性粒细胞计数增高应警惕EG;EG内镜表现无特异性,主要以胃常见;内镜下活检可见大量嗜酸粒细胞浸润;浆膜型患者腹水可见大量嗜酸粒细胞浸润;激素治疗与非激素治疗疗效良好,激素治疗组嗜酸粒细胞下降明显,复发用药亦有效.结论 EG临床表现无特异性,易漏诊和误诊,内镜活组织检查和腹水见大量嗜酸粒细胞是诊断的关键,糖皮质激素是首选的治疗药物.     

Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using [125I]iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissue featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.     

A case of intrabronchial dissemination of candida pseudohyphae presenting as respiratory failure]

A 63-year-old man was admitted to our hospital because of fever, skin eruption, leukocytopenia and liver dysfunction. He was receiving H2-blocker for gastric ulcer of the time he developed his symptoms. The H2-blocker was discontinued because of its possible association with leukocytopenia, and steroids were administered. On the 4th day of hospitalization, he suddenly developed expiratory wheeze and dyspnea, resembling an asthmatic attack. WBC was 400/mm3 with 65% neutrophils. Chest X-ray showed hyper inflation and increased thickness of bronchiolar walls. Bronchodilators had no effect and the patient died of respiratory failure on the 8th day. At autopsy, most bronchioles were filled with candida pseudohyphae. The large airways and lung parenchyma were not involved, except for focal bacterial pneumonia. Histological findings suggestive of bronchial asthma such as constriction of bronchial smooth muscle or infiltration of eosinophils were not observed Candida infection was also found in the pharynx, stomach, bowel, and kidneys. Candidiasis is becoming a more important contributory cause of death in compromised hosts. Although rare, this case suggests that patients with bronchopulmonary candidiasis present with expiratory wheeze resembling asthmatic attack.     

Agonist-independent alteration in beta-adrenoceptor-G-protein-adenylate cyclase system in an equine model of recurrent airway obstruction

We examined the inhibitory sympathetic beta-adrenergic mechanisms in peripheral lung, bronchi and trachea of an equine model of recurrent airway obstruction (RAO), to support the hypothesis that the beta-adrenergic receptor dysfunction is not only restricted to cell surface receptor density but rather encompasses a mechanistic defect apart from the receptor, to the intracellular signaling components. The non-asthmatic lung possessed 3.2-fold more beta-adrenergic receptors than bronchi (496 +/- 19.4 vs. 155.1+/- 19.6 fmol/mg protein; P < 0.01) and 6.2-fold higher than in the trachea (79.8 +/- 12.6 fmol/mg protein; P < 0.001) (assessed by radioligand binding assays using (-)-[(125)I]-iodocyanopindolol, ICYP) and in all tissues a greater proportion of the beta(2)- than the beta(1)-subtype (75-80%). The receptor density (B(max)) in lung parenchyma and bronchial membranes was 33 and 42%, respectively, lower (P < 0.001) in RAO than in control animals, attributable to a decrease in the beta(2)-subtype. This receptor down-regulation was accompanied with an attenuated coupling efficiency of the receptor to the stimulatory G(S)-protein (P < 0.05 vs. control). Concomitantly, activation of adenylate cyclase evoked by isoproterenol was significantly reduced in lung and bronchial membranes of animals with RAO, whereas effects of 10 microM GTP, 10mM NaF, 10 microM forskolin and 10 mM Mn(2+) were not altered. There was no difference in beta-adrenergic receptor density, G(S)-protein or adenylate cyclase coupling in the trachea between asthmatic and control animals. In conclusion, in stable asthma the pulmonary beta-adrenergic receptor-G(S)-protein-adenylate cyclase system is impaired, thus the pathologic process involves all signaling components, and due to its close similarity, this animal model seems to serve as a suitable model, at least partly, of chronic asthmatic patients.     

Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack.

To examine the changes in airways in bronchial asthma (BA) during an asthma attack causing death, we performed morphometric analysis of autopsied lungs from three outpatients who died of severe acute asthma attacks (group A) and compared these to five patients who died of non-status asthmaticus (group B). Controls (group NL) were four patients who died of diseases other than respiratory disorders. Area proportions of bronchial glands to bronchial wall (gland [percent]) and of goblet cells to total epithelial layer (goblet [percent]) and the intraluminal amount of mucus in the airways (MOR) were measured in a paraffin section. There were no significant differences in age, sex, smoking history, duration of BA history, and dosage of glucocorticoids received between groups A and B. Although both groups A and B showed significantly larger values of gland (percent) in the central airways and of inflammatory cell numbers in the airway walls than did group NL, no significant differences were observed between groups A and B. In contrast, markedly significant increases in goblet (percent) and in MOR were observed in group A compared to groups B and NL. These increases in group A were more dominant in the peripheral airway: 30-fold and threefold increases of group B in goblet (percent) and MOR, respectively. Furthermore, MOR significantly correlated with goblet (percent) in the peripheral airways (p less than 0.05). These findings suggest that a marked increase in goblet cells of the airways is a feature characteristic of patients with BA who die of a severe acute attack.     

尿紧张素Ⅱ在支气管哮喘气道重塑中的作用

目的观察支气管哮喘(简称哮喘)大鼠及哮喘患者支气管管壁尿紧张素Ⅱ(UⅡ)的变化,探讨UⅡ在哮喘发病及气道重塑中的作用。方法将20只一级雄性Wistar大鼠分为对照组和哮喘组,每组10只。哮喘组大鼠采用卵白蛋白10mg腹腔内注射及雾化吸入(5mg)处理建立大鼠哮喘模型;肺组织切片经苏木精伊红(HE)染色,采用图像分析技术测量大鼠支气管管腔的内周长(Pi)、管壁面积(WA)、平滑肌面积(WAm),以WA/Pi和WAm/Pi反映其气道重塑情况;对哮喘大鼠和5例哮喘患者肺组织切片采用链亲和素蛋白过氧化物酶(SP)免疫组织化学法染色检测支气管UⅡ的表达变化,以灰度扫描和计数UⅡ阳性染色细胞数判断其表达强度。结果哮喘组大鼠WA/Pi、WAm/Pi分别为(24.1±2.4)μm2/μm、(5.3±1.9)μm2/μm,与对照组[(16.5±1.7)μm2/μm、(3.8±1.2)μm2/μm]比较差异有统计学意义(t分别=3.892、3.785,P均<0.01);哮喘大鼠支气管UⅡ的表达强度为2.46±0.15,与对照组(1.26±0.11)比较差异有统计学意义(t=6.236,P<0.01);UⅡ的表达强度与WAm/Pi呈正相关(r=0.712,P<0.01);UⅡ阳性染色细胞百分数为(82±8)%,与对照组[(22±8)%]比较差异也有统计学意义(t=19.102,P<0.01);哮喘患者支气管UⅡ的表达强度为2.61±0.19,与对照组(1.36±0.12)比较差异有统计学意义(t=7.374,P<0.01);UⅡ阳性染色细胞百分数为(75±9)%,与对照组[(27±7)%]比较差异有统计学意义(t=16.236,P<0.01)。结论哮喘气道UⅡ的表达和合成明显增加,其可能与哮喘发病及其气道重塑具有密切的关系。     

Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine.

Bronchial hyperresponsiveness can be demonstrated in asthmatic subjects by inhalation of adenosine, but the action of adenosine at the level of the human airway smooth muscle has received comparatively little attention. We have previously observed that bronchi isolated from one asthmatic patient contracted in response to adenosine. We have therefore, during the course of a 3-yr study, further characterized the effects of adenosine in bronchi prepared from surgical specimens of lung tissue of asthmatics and of nonasthmatics. Contraction responses were always studied in vitro the same day the tissues were obtained. Bronchi from asthmatics (19 strips from six patients) were more sensitive to adenosine than were bronchi from nonasthmatics (21 strips, seven patients). In contrast, there was no difference in sensitivity to histamine or leukotriene C4 between the two groups, nor was the maximal tissue contractility different. The contractile effect of adenosine was inhibited by the adenosine A1-antagonist 2-thio-[(1,3-dipropyl)-8-cyclopentyl]-xanthine as well as by the dual A1 and A2 antagonists 8-(p-sulfo)-phenyltheophylline and theophylline. The combination of leukotriene antagonism (receptor-antagonist ICI 198,615 or biosynthesis inhibitor MK-886) and histamine antagonism (antihistamines mepyramine and metiamide) blocked the contractile effects of adenosine, suggesting that adenosine acts indirectly by liberation of leukotrienes and histamine, possibly from mast cells. The findings of increased sensitivity to adenosine in bronchi from asthmatics to our knowledge represents the first evidence of increased bronchial reactivity in vitro in asthmatics.     

Inhalation of polymyxin B as a bronchial provocation method

With the exception of allergen inhalation, current bronchial provocation tests do not elicit a reaction identical to an asthmatic attack because the first stage of the latter — degranulation of mast cells — does not occur. In order to detect bronchial hyperreactivity and to determine the role of mast cells, polymyxin B — a histamine releasing agent — was administered by inhalation to 49 asthmatic patients and the resulting bronchospasm compared with that induced by histamine and exercise. Inhalation of disodium cromoglycate (Intal®) inhibited the response to polymyxin B. Polymyxin B probably acts on mast cells in lung tissue. Inhalation of polymyxin B appears to be useful as a method for detection of bronchial hyperreactivity.     

支气管活检标本的端粒酶活性检测对肺癌的诊断价值

目的：探讨肺癌组织端粒酶活性检测对肺癌的诊断价值。方法采用端粒酶重复序列扩增法检测纤维支气管镜活组织检查的肺癌病变组织（７０例）、肺癌对侧支气管组织（７０例）及非癌性肺疾病支气管组织（２０例）的端粒酶活性,并和病理学及细胞学检查结果进行比较。结果肺癌病变组织端粒酶检出率为８１％,明显高于肺癌对侧支气管组织（１４％）（Ｐ〈０．０１）及非癌性肺疾病支气管组织（１０％）的检出率（Ｐ〈０．０１）;肺癌组织     

Clinical and experimental studies on fibronectin in bronchial asthma

BackgroundClinical and experimental studies were performed to investigate the kinetics of fibronectin (FN) and its clinical significance in bronchial asthma.MethodsMeasurements of plasma fibronectin (PFN) and sputum fibronectin (SFN) were performed in asthmatic patients. Eosinophil chemotaxis, adherence and activation activity to FN were measured. An animal model of bronchial asthma was created and lung tissues were analyzed by immunohistochemical staining.ResultsCompared with periods without an asthmatic attack, the PFN level was significantly lower during periods with more severe asthmatic attacks in 15 patients with bronchial asthma. In contrast, the SFN level was significantly higher during periods with more severe asthmatic attacks. In a guinea pig model of asthmatic bronchitis, FN was positively stained in the subepithelial or submucosal tissue and abraded epithelial cells in the alveolar space during asthmatic attacks. Marked eosinophilic infiltration was also noted in the same tissues and cells. A negative correlation was noted between the number of peripheral eosinophils and the PFN level. In contrast, a positive correlation was noted between the number of sputum eosinophils, which reflects the severity of asthmatic attacks, and the SFN level. An experimental study was performed to investigate the relationship between eosinophils and FN. A positive relationship was noted between eosiophil chemotaxis, increased adherence of activated eosinophils and FN levels.ConclusionsIt is suggested that FN may enhance allergic reactions at an early or acute phase of bronchial asthma.     

哮喘猝死患者的心肺病理分析

目的 提高对哮喘猝死的认识，了解其心、肺病理学特征和死亡原因。方法 对14例哮喘猝死患者的病理资料进行分析。结果 哮喘猝死患者无性别差异，年龄30岁以下者9例（64．3％）；病理改变的特点为支气管管壁嗜酸细胞浸润14例（100％），粘膜基底膜增厚12例（85．7％），支气管平滑肌细胞增生11例（78．6％），粘液腺增生、肥大9例（64．3％），细支气管内粘液栓形成8例（57．1％）；左心室壁瘢痕形成10例（71．4％），病变主要位于左心室侧壁和心尖部。结论 哮喘猝死患者气道存在明显的非特异性炎症反应、心肌受损和细支气管粘液栓形成为其主要致死原因。