Monoclonal Antibodies and Airway Diseases

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.     

Mitochondria in the Center of Human Eosinophil Apoptosis and Survival

Eosinophils are abundantly present in most phenotypes of asthma and they contribute to the maintenance and exacerbations of the disease. Regulators of eosinophil longevity play critical roles in determining whether eosinophils accumulate into the airways of asthmatics. Several cytokines enhance eosinophil survival promoting eosinophilic airway inflammation while for example glucocorticoids, the most important anti-inflammatory drugs used to treat asthma, promote the intrinsic pathway of eosinophil apoptosis and by this mechanism contribute to the resolution of eosinophilic airway inflammation. Mitochondria seem to play central roles in both intrinsic mitochondrion-centered and extrinsic receptor-mediated pathways of apoptosis in eosinophils. Mitochondria may also be important for survival signalling. In addition to glucocorticoids, another important agent that regulates human eosinophil longevity via mitochondrial route is nitric oxide, which is present in increased amounts in the airways of asthmatics. Nitric oxide seems to be able to trigger both survival and apoptosis in eosinophils. This review discusses the current evidence of the mechanisms of induced eosinophil apoptosis and survival focusing on the role of mitochondria and clinically relevant stimulants, such as glucocorticoids and nitric oxide.     

呼出气冷凝液白三烯、8异前列腺素、硝酸盐/亚硝酸盐检测在哮喘中的应用及孟鲁司特对炎症指标的影响

目的: 观察支气管哮喘患者呼出气冷凝液(EBC)中半胱氨酰白三烯C4(LTC4)、8异前列腺素(8-isoprostane)、硝酸盐/亚硝酸盐(NO₂ /NO₃)水平及孟鲁司特干预前后炎症指标的变化。 方法: 选择哮喘非急性发作期患者30例,均予孟鲁司特 10 mg,每晚一次口服,疗程1月,分别于治疗前及治疗后检测EBC中LTC4、8-isoprostane、NO₂/NO₃水平,另选择30例健康人为健康对照组。 结果: 哮喘组LTC4(55±17) ng/mL、8-isoprostane(13±9) ng/mL、NO₂/NO₃(4.2±1.2) ng/mL显著高于正常对照组(17±17)、(7±6)、(3.2±0.6) ng/mL(均P<0.01)。哮喘组治疗前LTC4 (55±17) ng/mL显著高于治疗后(38±14) ng/mL,P<0.01。哮喘组治疗前8-isoprostane (13±9) ng/mL,高于治疗后(11±6) ng/mL,但差异无统计学意义(P>0.05)。哮喘组治疗前NO₂/NO₃水平为(4.2±1.2) ng/mL,治疗后为(4.1±1.4) ng/mL,差异无统计学意义(P>0.05)。 结论: 检测哮喘患者EBC中LTC4、8-isoprostane、NO₂/NO₃水平可简便安全监测哮喘的气道炎症,孟鲁司特能降低EBC中LTC4水平,是一种有效的气道炎症抑制剂。     

香菇多糖对卵白蛋白诱导小鼠哮喘模型树突细胞TIM4表达及炎症影响

目的: 研究香菇多糖治疗卵白蛋白（OVA）诱导小鼠哮喘模型后树突状细胞TIM4表达情况及炎症影响。方法: 将Balbc雌性小鼠随机分为三组：正常对照组、哮喘模型组、香菇多糖治疗组。OVA诱导激发小鼠哮喘模型,治疗组于第7天起每天进行香菇多糖腹腔注射治疗,哮喘模型组用生理盐水替代香菇多糖进行腹腔注射。分离脾脏单个核细胞,流式细胞学术检测树突细胞TIM4表达;ELISA检测血清IL-4和MCP-1浓度;Q-PCR检测肺组织中TIM4表达;肺组织HE染色。结果:治疗后,治疗组能下调脾脏树突细胞TIM4表达（P<0.05）,降低血清中MCP-1、IL-4浓度（P<0.05,P<0.01）。肺组织中TIM4的RNA表达量下降（P<0.05）。HE染色显示治疗组肺组织炎症浸润明显减轻。结论: 香菇多糖能通过下调树突细胞TIM4表达,降低炎症因子IL-4、MCP-1等浓度,抑制OVA哮喘模型的炎症反应。     

枸杞果多糖对哮喘小鼠炎症损伤影响及作用机制

目的 探究枸杞果多糖对Ⅴ级卵清蛋白(OVA)诱导的哮喘小鼠模型炎症损伤影响及其作用机制.方法 以OVA诱导的哮喘小鼠为模型,并进行枸杞果多糖干预.肺组织苏木素-伊红(HE)染色、流式细胞术检测肺组织嗜酸性粒细胞水平反映炎症细胞浸润程度;肺组织马松(masson)染色检测肺组织纤维化程度,过碘酸-雪夫(PAS)染色检测支...     

竖井型城市隧道自然通风哮喘效应模型研究

在前期竖井型城市隧道自然通风模型实验研究的基础上,通过改变实验模型,研究了竖井"哮喘效应"产生的原因,以及如何克服"哮喘效应"的办法,得出"哮喘效应"是连续竖井通风的必然产物,是不能阻止的结论。     

平喘汤与舒利迭对支气管哮喘缓解期疗效比较的研究

目的:通过平喘汤与舒利迭疗效比较,探讨哮喘缓解期中药治疗的意义.方法:选择我院门诊哮喘缓解期患者178例,分为中药组、舒利迭组、对照组,通过临床症状控制率、肺功能指标、诱导痰嗜酸性粒细胞计数百分比及血清IgE指标的治疗前后比较,研究平喘汤对缓解期哮喘息者的疗效.结果:中药组与舒利迭组中,上述四方面指标治疗前后都有显著差...     

Analysis of short-term influences of ambient aeroallergens on pediatric asthma hospital visits

The objective of our study was to investigate the association between daily pediatric asthma hospital visits and daily concentrations of aeroallergens and their specific species. Records of daily asthma visits in Cincinnati area were retrieved from Cincinnati Children's Hospital Medical Center and aeroallergen sampling was performed by the Button Inhalable Sampler. The Poisson generalized linear model was carried out in which the log of the number of asthma hospital visits was related to aeroallergen level, treated as a continuous variable with adjustment for seasonal time trend, day of the week, ozone and PM(2.5) concentrations, temperature and humidity. The aeroallergens having a significant impact on asthma hospital visits were ragweed, oak/maple and Pinaceae pollen. Their relative risks on asthma hospital visits with respect to a 100 counts/m(3) increase in concentration were in the range of 1.23 to 1.54. The effects in causing the asthma exacerbation were delayed by 3 or 5 days.     

PVC--as flooring material--and its association with incident asthma in a Swedish child cohort study

The Dampness in Buildings and Health study (DBH) started in the year 2000 in V?rmland, Sweden, with a baseline questionnaire sent to all children (n = 14,077) aged 1-6. Five years later, a follow-up questionnaire was sent to the children who were 1-3 years at baseline. A total of 4779 children participated in both the baseline and the follow-up studies and constitute the study population in this cohort study. The aim of this study was to examine the association between exposure to PVC-flooring in the child's and parent's bedroom in homes of children aged 1-3 and the incidence of asthma, rhinitis, and eczema during the following 5-year period. Adjusted analyses showed that the incidence of asthma among children was associated with PVC-flooring in the child's bedroom (AOR 1.52; 95% CI 0.99-2.35) and in the parent's bedroom (1.46; 0.96-2.23). The found risks were on borderline of significance and should therefore be interpreted with caution. There was further a positive relationship between the number of rooms with PVC-flooring and the cumulative incidence of asthma. PVC-flooring was found to be a stronger risk factor for incident asthma in multifamily homes when compared with single-family houses and in smoking families compared with non-smoking families and in women. PRACTICAL IMPLICATIONS: These longitudinal data from the DBH study found an association between the presence of PVC-flooring in the home and incident asthma in children. However, earlier results from the DBH study have shown that PVC-flooring is one important source for phthalates in indoor dust, and exposure to such phthalates was found to be associated with asthma and allergy among children. This emphasizes the need for prospective studies that focus on the importance of prenatal and neonatal exposure to phthalates in the development of asthma and allergy in children.     

诱导性支气管相关淋巴组织（iBALT）形成与相关肺疾病的研究

肺是人体的呼吸器官,肺的呼吸作用使机体和外界进行气体交换,以维持机体的生命活动。肺的生理特性会使肺黏膜表面接触外界的有害刺激物,包括病原体、过敏原、有害气体和烟雾颗粒,这些可能导致肺部损伤和感染。在肺部炎症的诱导下,肺中的免疫细胞（B淋巴细胞和T淋巴细胞）聚集在肺支气管的周围,形成诱导性支气管相关淋巴组织（iBALT）。研究发现iBALT参与哮喘、慢性阻塞性肺病、肺癌等多种肺部疾病的病理发展。iBALT受到多种细胞因子表达调控,但是形成过程以及对疾病的影响尚不明确。本文旨在综述iBALT的形成因素以及在肺中的病理状况,为肺部慢性炎症疾病提供新的治疗思路。