IL-12和支气管哮喘

支气管哮喘是一种气道慢性炎症性疾病。越来越多的事实表明,哮喘的发生与内源性IL-12生成不足有关。IL-12无论单独应用还是作为免疫佐剂,均可逆转哮喘动物模型体内Th1/Th2失衡和抑制气道变态反应性炎症。该文综述了IL-12的生物学效应、IL-12与哮喘的关系、IL-12在哮喘治疗中的作用及其应用。     

真菌过敏性哮喘的治疗研究进展

真菌过敏性哮喘是由环境中真菌致敏原暴露诱导的一种呼吸道慢性炎症性疾病。真菌过敏哮喘患者肺部炎症细胞、结构细胞及细胞组分间有复杂的相互作用,使得患者气道壁重塑并伴渐进性肺功能障碍,表现为喘息、胸闷、呼吸困难等症状,对患者的工作和生活造成严重影响,而目前糖皮质激素及抗菌药物等传统疗法对其治疗效果欠佳。近年来,很多研究开始致力于对真菌过敏性哮喘新的治疗方法进行积极探索,使得真菌过敏性哮喘的治疗除应用糖皮质激素等传统方法外,在抗真菌感染及其免疫学治疗控制真菌过敏性哮喘方面取得一定新进展。     

Assessment of some oxidative stress parameters in patients with bronchial asthma after selenium supplementation

The goal of this study was to investigate the effect of selenium deficit replenishment in patients with bronchial asthma (BA) on manifestations of oxidative stress and conditions of the antioxidant system (AOS). The need of correction of selenium deficit in BA-patients is determined by increased requirements in antioxidants due to chronic inflammatory process responsible for pathogenesis of BA. Latvia as well as Eastern Finland, Byelorussia, some regions of Ukraine, North-Western Russia, and New Zealand belong to the endemic areas with marked selenium deficit in soils and foodstuff. Twenty patients (7 men and 13 women) with selenium deficit and verified diagnosis of BA have been examined. In addition to basic therapy all patients received organic selenium as SelenoPRECISE (PharmaNord) 200 μg daily for 16 weeks. This caused statistically significant increase of plasma selenium from 50.94 ± 7.58 to 63.59 ± 10.87 μg/l (p < 0.001), the increase of selenium-dependent glutathione peroxidase (from 38.64 ± 10.72 U/g Hb to 58.57 ± 14.64 U/g Hb, p = 0.01). Treatment of patients with selenium also normalized the parameters characterizing oxidative stress (chemiluminescence), significantly exceeded normal values before this treatment. The use of selenium in addition to basic therapy allows to abolish or reduce oxidative stress by correcting the antioxidant system.     

Correlation of exhaled breath temperature with bronchial blood flow in asthma

In asthma elevated rates of exhaled breath temperature changes (Δe°T) and bronchial blood flow (Q_aw) may be due to increased vascularity of the airway mucosa as a result of inflammation.We investigated the relationship of Δe°T with Q_aw and airway inflammation as assessed by exhaled nitric oxide (NO). We also studied the anti-inflammatory and vasoactive effects of inhaled corticosteroid and β₂-agonist.Δe°T was confirmed to be elevated (7.27 ± 0.6 Δ°C/s) in 19 asthmatic subjects (mean age ± SEM, 40 ± 6 yr; 6 male, FEV₁ 74 ± 6 % predicted) compared to 16 normal volunteers (4.23 ± 0.41 Δ°C/s, p < 0.01) (30 ± 2 yr) and was significantly increased after salbutamol inhalation in normal subjects (7.8 ± 0.6 Δ°C/ s, p < 0.05) but not in asthmatic patients. Q_aw, measured using an acetylene dilution method was also elevated in patients with asthma compared to normal subjects (49.47 ± 2.06 and 31.56 ± 1.6 μl/ml/min p < 0.01) and correlated with exhaled NO (r = 0.57, p < 0.05) and Δe°T (r = 0.525, p < 0.05). In asthma patients, Q_aw was reduced 30 minutes after the inhalation of budesonide 400 μg (21.0 ± 2.3 μl/ml/min, p < 0.05) but was not affected by salbutamol.Δe°T correlates with Q_aw and exhaled NO in asthmatic patients and therefore may reflect airway inflammation, as confirmed by the rapid response to steroids.     

Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients

Background

The clinical manifestations of severe asthma are heterogeneous. Some individuals with severe asthma develop irreversible fixed airway obstruction, which is associated with poor outcomes. We therefore investigated the factors associated with fixed airway obstruction in Korean patients with severe asthma.

Methods

Severe asthma patients from a Korean adult asthma cohort were divided into two groups according to the results of serial pulmonary function tests. One group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had reversible airway obstruction (RAO) [FEV1/FVC ratio ≥ 0.7, n = 116]. Clinical and demographic parameters were compared between the two groups.

Results

Multivariate analysis showed that longer duration of disease, greater amount of cigarette smoking and absence of rhinosinusitis were significantly related to the development of FAO in severe asthmatics. Other parameters, including atopic status, pattern of airway inflammatory cells in induced sputum, and frequency of asthma exacerbations did not differ between the FAO and RAO groups.

Conclusion

Severe asthma patients with longer disease duration and the absence of rhinosinusitis are more likely to develop FAO. This study also demonstrates the importance of quitting smoking in order to prevent irreversible airway obstruction. Further investigation is required to determine the mechanism by which these factors can modify the disease course in Korean patients with severe asthma.     

The effect of house design and environment on fungal movement in homes of bronchial asthma patients

The effect of house building design and environment on the fungal movement in the houses of 41 bronchial asthma (BA) patients has been investigated by examining house dust. The presence and composition of fungi were determined and compared in relation to building structure, house age, size of living room, main flooring material, presence of a living-room rug or air purifier, and frequency of vacuum cleaning. Among these elements, fungal CFU apparently varied only between building structure: wooden-board houses had significantly higher numbers of fungi than reinforced concrete houses (p < 0.01), and wooden mortar or iron-framed prefabricated houses had significantly higher numbers of fungi than reinforced concrete houses (p < 0.05). Classification of the types of fungi present in the house dust of BA patients showed that, regardless of the building designs, there were high levels of osmophilic fungi (group A) and fungi that survive at relatively dry conditions (group B), whereas fungi that survive in very wet conditions (group D) were present at low frequency. This revised version was published online in August 2006 with corrections to the Cover Date.     

银杏叶提取物对豚鼠哮喘模型血红素氧合酶-1表达的影响

目的探讨银杏叶提取物(Egb761)对豚鼠哮喘模型血红素氧合酶-1(HO-1)表达的影响.方法 将30只豚鼠随机分为3组(n=10)(1)正常组;(2)哮喘组;(3)治疗组.测定全血一氧化碳血红蛋白(COHb)的百分比含量、气道阻力并观察气道壁嗜酸性粒细胞(EOS)浸润情况, 用免疫组织化学染色方法观察HO-1在豚鼠肺组织中的表达变化.结果各组气道上皮细胞HO-1阳性表达的平均吸光度分别为 0.170±0.020、0.707±0.058、0.397±0.034.哮喘组HO-1的表达水平显著高于正常组(P<0.01).治疗组HO-1的表达水平显著低于哮喘组(P<0.01). 结论银杏叶提取物能显著抑制哮喘豚鼠气道壁内上皮细胞HO-1的表达,提示银杏叶提取物抑制HO-1的表达可能是银杏叶提取物治疗哮喘的作用机制之一.     

染料木黄酮对哮喘豚鼠肺部炎症和气道重塑的预防作用

目的：研究蛋白酪氨酸激酶（PTK）抑制剂染料木黄酮对哮喘豚鼠肺部炎症和气道重塑的作用。方法：成年雄性豚鼠30只,随机分成3组（n=10）：对照组（C组）、哮喘组（A组）和染料木黄酮干预组（B组）,以腹腔内注射联合雾化吸入卵蛋白复制哮喘模型。测支气管肺泡灌洗液（BALF）中细胞总数及其分类数,测细支气管炎症细胞浸润及支气管重塑指标,免疫纽化方法测磷酸化酪氨（p-tyrosine）在肺组织中的表达。结果：A组BALF中细胞总数、嗜酸性粒细胞分类与C组比较明显增加,B组与A组比较明显降低,差异有统计学意义（P〈0．01）;A组细支气管嗜酸性粒细胞（E）数和淋巴细胞（L）数较C组明显增多,B组与A组比较明显降低,差异有统计学意义（P〈0．01）;B组细支气管重塑较A组明显减轻（P〈0．01）,与C组比较,差异无统计学意义（P〈0．05）;免疫组化显示p-tyrosine在支气管平滑肌、支气管上皮、血管滑平滑肌及炎性细胞均有表达,尤其以支气管和血管平滑肌及炎性细胞明显,A组比C组表达明显增高,差异有统计学意义（P〈0．01）,而B组与C组比较,无明显差别（P〉0．05）。结论：PTK对哮喘豚鼠肺部炎症和支气管重塑具有促进作用：PTK抑制剂染料木黄酮对哮喘豚鼠肺炎症和支气管重塑具有预防和抑制作用。     

Th22细胞与支气管哮喘

支气管哮喘是一种临床上常见的呼吸道疾病,研究发现CD4＋T细胞在哮喘的发病过程中起重要作用。Th22细胞是最近发现的一类CD4＋T细胞功能亚群之一,其主要效应因子IL-22在炎症性疾病、组织修复、创口愈合及自身免疫性疾病中起重要作用,但其具体机制尚未完全清楚。从Th22的细胞因子来源、生物学特性、分化和调控出发,简要探讨Th22细胞与哮喘之间的可能关系。     

Human bronchial smooth muscle responsiveness after in vitro exposure to oxidizing pollutants

The aims of this work were (1) to determine the dose-response relationship between ex vivo exposure to oxidizing pollutants such as nitrogen dioxide (NO₂), the aldehyde acrolein, and ozone (O₃), and the reactivity to agonists in isolated human bronchial smooth muscle; and (2) to investigate the alterations in the cellular mechanisms of human airway smooth muscle contraction induced by such exposures. Experiments were performed in isolated human bronchi obtained at thoracotomy. Isometric contraction in response to a variety of agonists was compared between pollutant-exposed preparations and paired controls. Short exposures to NO₂, acrolein, or O₃ altered the subsequent airway smooth muscle responsiveness in a dose-dependent manner. The cellular mechanisms producing the airway hyperresponsiveness observed in vitro are shared by the three pollutants and include alterations in airway smooth muscle excitation-contraction coupling as well as indirect effects on neutral endopeptidase activity.Abbreviations ACh acetylcholine - CCRC cumulative concentration-response curve - KH Krebs-Henseleit solution - NEP neutral endopeptidase - NKA neurokinin A - SP substance P     

Effect of Fructus schisandrae syrup on bronchial asthma mice model

Purpose

To investigate the effect of Fructus schisandrae syrup on bronchial asthma mice model.

Relation of indoor heating with asthma,allergic sensitisation,and bronchial responsiveness: survey of children in south Bavaria.

OBJECTIVE--To investigate the relation between different types of heating and the prevalence of atopic diseases, skin test reactivity, and bronchial hyperresponsiveness. DESIGN--Cross sectional survey among school-children aged 9-11 years. Skin prick tests, pulmonary function tests, and bronchial challenge in the children and self completion of a written questionnaire by the children''s parents. SUBJECTS--1958 children in a rural area in southern Bavaria, Germany. MAIN OUTCOME MEASURES--Prevalence of asthma, hay fever, and atopic dermatitis as determined by parents'' answers to a questionnaire; the atopic status of the child assessed by skin prick tests; and bronchial responsiveness to cold air challenge in the children. RESULTS--After possible confounders were controlled for, the risk of developing hay fever (odds ratio = 0.57; 95% confidence interval 0.34 to 0.98), atopy defined as at least one positive reaction to a panel of common aeroallergens (0.67; 0.49 to 0.93), sensitisation to pollen (0.60; 0.41 to 0.87), and of bronchial hyperresponsiveness (0.55; 0.34-0.90) was significantly lower in children living in homes where coal or wood was used for heating than in children living in homes with other heating systems. CONCLUSIONS--Factors directly or indirectly related to the heating system used in rural Bavarian homes decrease the susceptibility of children to becoming atopic and to developing bronchial hyperresponsiveness.     

Release of RANTES from nasal and bronchial epithelial cells

RANTES is a chemokine with eosinophil attractant and activating activities. This study was undertaken to determine whether primary cultures of human nasal and primate bronchial epithelial cells produce RANTES and the effect of various cytokines and dexamethasone on the release of this chemokine. Nasal epithelial cells from 32 patients (HNE) and bronchial epithelial cells from 17 Macaca nemestrina monkeys (PBE) were cultured in vitro for 24 to 72 h with LPS, TNF-, IL-1, IFN- and TNF- combined with IFN- and/or dexamethasone at 10 to 1000 µg/ml. Culture supernatants were assayed for RANTES by ELISA. RANTES synthesis was measured by immunoprecipitation. HNE and PBE released modest constitutive amounts of RANTES (350 to 1000 pg/ml) which did not increase with time in culture. Release of RANTES was stimulated by all activators except LPS in a time-dependent manner, with the greatest synthesis induced by the combined addition of TNF- and IFN-. The combination of these activators also increased RANTES synthesis as determined by immunoprecipitation. Dexamethasone at 100 and 1000 µg/ml produced significant inhibition of stimulated RANTES release. These data indicate that normal nasal and bronchial epithelial cells release RANTES which is upregulated by various cytokines and inhibited by dexamethasone. The enhanced release is due to stimulation of both synthesis and secretion. Production of RANTES by epithelial cells could contribute to the inflammation that characterizes the respiratory tract in asthma and rhinitis and downregulation of RANTES by glucocorticoids may be one mechanism of the therapeutic effect of these agents.     

Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma

Allergic asthma rates have increased steadily in developed countries, arguing for an environmental aetiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics--streptomycin and vancomycin--and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect on the microbiota and on disease, whereas vancomycin reduced microbial diversity, shifted the composition of the bacterial population and enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the 'hygiene hypothesis', our data support a neonatal, microbiota-driven, specific increase in susceptibility to experimental murine allergic asthma.     

细胞信号转导与X连锁的非特异性精神发育迟滞

非特异性精神发育迟滞是患者仅表现出一般或特殊认知功能障碍的一种病症。对相关的基因及其生理功能进行研究,不仅对弄清非特异性精神发育迟滞的遗传基础有重要意义,还能揭示人类认知功能的分子遗传机理。文章对一些涉及X连锁的非特异精神发育迟滞的基因,其表达产物同时参与细胞信号转导的信号分子,如跨膜受体、鸟苷酸相关蛋白和激酶的生理功能及其研究现状进行了阐述,揭示了细胞信号转导与人类认知活动之间的密切关系,为精神发育迟滞的治疗或预防提供新思路。     

Contribution of anaphylatoxins to allergic inflammation in human lungs

The contribution of complement activation to allergic asthma remains controversial. In order to elucidate the role played by the complement split products, anaphylatoxins C3a and C5a, we evaluated their effects on production of cysteinyl-leukotrienes (cysLTs) by human lung fragments following an anaphylactic reaction. The lung tissues obtained from two patients with lung cancer showed C5aR-, C5L2R-, and C3aR-mRNA expression. When the chopped lung fragments passively sensitized with human IgE were incubated with anti-human IgE antibody, a significant amount of cysLTs was generated in comparison with the control (without anti-IgE antibody). The co-addition of human C5a at doses of 0.1 to 10 ng/ml to the anti-IgE antibody potentiated cysLT production. The response was bell-shaped in distribution, significant, and peaked at a C5a concentration of 1 ng/ml. The co-addition of human C3a up to 1,000 ng/ml seemed to increase cysLT production, but not to any significant extent. A novel C5a receptor complementary peptide, acetylated peptide A, dose-dependently inhibited cysLT production by the human lung fragments following the anaphylactic reaction in the presence of 1 ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma, thus acetylated peptide A may be useful for suppressing allergic inflammation in the lungs.     

Association of allergic bronchial asthma with certain air pollutants and weather parameters

Student bronchial asthma at the University of Minnesota was studied in grain sensitive and in control groups to find the influence of air pollutants from nearby grain installations on this problem.Under relatively high dust conditions it was observed that grain sensitive students had a two-fold increase in asthma attacks while the controls showed no significant changes. A combined association of wind direction and relatively high dust conditions with asthma gave a correlation of higher significance in the grain sensitive group. Multiple associations indicated that this relationship is only weakly affected by seasonal and temperature changes. It was also observed that relative humidity conditions may significantly influence the effectiveness of the dust exposure in sensitive students. Weather parameters showed no association with asthma in the control group.

---

Zusammenfassung Bronchialasthma bei Studenten der Universität Minnesota wurde bezüglich der Empfindlichkeit gegen Getreidesamen mit Kontrollgruppen untersucht, um den Einfluss der in der Luft befindlichen Pollen durch nahe gelegene Getreidefelder zu finden. Unter verhältnismässig hohen Konzentrationen wurde beobachtet,dass gegen Getreidesamen empfindliche Studenten doppelt so viele Asthmaanfälle hatten, wie die Kontrollgruppe, die keine signifikante Änderung zeigte. Eine Verbindung von Windrichtung und relativ hohen Staubkonzentrationen mit Asthmaanfällen ergab eine Korrelation von höherer Signifikanz in der sensiblen Gruppe. Weitere Zuordnungen zeigten, dass diese Beziehung nur wenig durch Änderungen von Jahreszeit und Temperatur beeinflusst wird. Es wurde auch beobachtet, dass die Relative Feuchte die Empfindlichkeit gegen Pollen bei entsprechend sensibilisierten Studenten beeinflussen kann. In der Kontrollgruppe zeigten Wetterparameter keine Beziehung zum Asthma.

---

Resume On a étudié les accès d'asthme bronchial provoqués par les polluants de l'atmosphère provenant d'entreprises travaillant les céréales et situées dans le voisinage du l'Université du Minnesota. Pour ce faire,on s'est servi d'étudiants de la dite Université sensibles aux poussières de céréales d'une part et d'un groupe de contrôle d'autre part. Dans des conditions de poussière relativement forte,on a observé que les étudiants sensibles aux poussières de céréales présentaient une fréquence double d'accès d'asthme alors que le groupe de contrôle n'était pas touché de façon significative. En utilisant une conbinaison des facteurs direction du vent et forte poussière d'une part, accès d'asthme d'autre part,on obtient une corrélation plus significative dans le groupe des gens sensibles.Des combinaisons multiples indiquent que cette corrélation n'est que peu influencée par la saison ou des changements de température. On a aussi remarqué que les conditions d'humidité relative peuvent influencer de façon significative la sensibilité effective aux poussières des étudiants du premier groupe. Quant au groupe de contrôle, on n'a pas trouvé de relation entre les accès d'asthme et les paramètres météorologiques.

---

---

Paper presented during the Fourth International Biometeorological Congress, New Brunswick, N.J., 26 August – 2 September 1966.This work was performed under Air Pollution Grant No. AP 00090-07,Division of Air Pollution, Bureau of State Services, United States Public Health Service.     

Arachidonic acid metabolites and their circadian rhythm in patients with allergic bronchial asthma

The aim of this study was to investigate circadian variation in concentrations of arachidonic acid (AA) metabolites in relation to the circadian pattern in bronchial patency. Blood samples were obtained at 4-hr intervals from 2000 of 1 day until 1400 of the next from 12 diurnally active asthmatic and six diurnally active non-asthmatic patients. Bloods were analyzed for the prostanoids thromboxane A2 (measured as stable metabolite 6-keto-PGF1a), PGE2 and PGF2a. Airways patency was assessed by self-measurement of peak expiratory flow (PEF). In asthmatics, circadian variation was detected in PEF as well as PGE2 and TXB2. The circadian trough of the PEF rhythm closely coincided with the circadian peak of the PGE2 and TXB2 rhythms. In the controls, the PEF was not circadian rhythmic. Of the AA metabolites only 6-keto-PGF1a exhibited 24-hr bioperiodicity in the controls. The controls exhibited a significantly higher circadian mean of PEF (P less than 0.001), while the asthmatics had a lower 24-hr average PGE2 but greater mean TXB2/PGE2 ratio. The obstructive effect caused by the overall 24-hr deficiency of PGE2 in asthmatics is possibly amplified by the increased of TXB2 during the early morning hours. This dissociation of the temporal patterns in TXB2 and PGE2 levels over the 24 hr is discussed as a characteristic finding for asthmatics.     

2007～2011年鄂州市气传致敏真菌调查及其与支气管哮喘的相关性

目的 探讨2007年5月～ 2011年4月鄂州市气传致敏真菌和支气管哮喘关系,以了解该地区支气管哮喘情况.方法 运用暴片调查法和暴皿调查法统计和记录鄂州市气传致敏真菌的种类及数量.选择该时期内鄂州市100例支气管哮喘患者采用真菌变应原浸液作过敏原皮试发现有35例患者皮内试验阳性,将35例发作期患者和40例稳定期支气管哮喘患者行曲霉特异性IgE测定.结果 100例支气管哮喘患者皮内实验组阳性35例,阳性率为35％,而在35例患者中IgE阳性有31例,检测符合率为88.58％,稳定期患者中阳性反应例数2例,阳性率为5％,两组阳性率比较差异具有显著性（P＜0.05）.结论 鄂州市气传致敏真菌和支气管哮喘密切相关,主要致病菌为曲霉,是支气管哮喘的致敏原之一,需要注意环境卫生以减少气传致敏真菌的数量.