TLR4 Asp299Gly、Thr399Ile基因多态性对变应性哮喘的发病及IgE水平的影响

目的　探讨TLR4 (toll likereceptor 4 )Asp2 99Gly、Thr399Ile基因多态性对变应性哮喘的发病和血浆IgE水平的影响。方法　利用聚合酶链反应 限制性片段长度多态性分析技术 (PCR RFLP) ,对 1 97例变应性哮喘患者和 1 5 6例健康人进行TLR4的Asp2 99Gly、Thr399Ile两位点的基因型检测。同时利用免疫发光法检测血浆IgE的水平。结果　 1 97例变应性哮喘患者TLR4基因Asp2 99Gly位点Asp Asp、Asp Gly和Gly Gly的基因型频率为 0 .81 7、0 .1 4 7和 0 .0 36 ,与正常对照组相比差异无统计学意义 (χ2 =0 .0 32 ,P =0 .984 ) ;但变应性哮喘患者Gly Gly、Asp Gly基因型血浆总IgE对数值 ( x±s:2 .6 1 5± 0 .6 0 0 1 ,n =36 )与Asp Asp基因型血浆总IgE对数值 ( x±s:2 .2 4 0± 0 .6 894 ,n =1 6 1 )相比较高 ,差异有统计学意义 (P =0 .0 0 2 )。TLR4基因Thr399Ile位点Thr Thr、Thr Ile和Ile Ile的基因型频率为 0 .970、0 .0 2 0和 0 .0 1 0 ,与正常对照组相比差异无统计学意义 (χ2 =0 .6 2 0 ,P =0 .733) ;变应性哮喘患者Ile Ile、Thr Ile基因型血浆总IgE对数值 ( x±s:2 .4 1 7± 0 .4 4 2 3,n =6 )与Thr Thr基因型血浆总IgE对数值 ( x±s:2 .30 5± 0 .6 94 9,n =1 91 )相比差异无统计学意义 (P =0 .5 71 )。     

Occupational asthma in bakeries caused by sensitivity to α-amylase

We report on a patient with asthma induced by occupational exposure to alpha-amylase derived from Aspergillus oryzae, which is a component of bread additives. A type I hypersensitivity to this enzyme was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an alpha-amylase extract.     

A 500‐ml plastic bottle: An effective spacer for children with asthma

Inhaled therapy using a metered‐dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI‐spacer delivery systems. A 500‐ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle‐spacer and discusses its advantages and limitations. It is concluded that a modified 500‐ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.     

变应性鼻炎、哮喘患者血白细胞介素的循证医学研究

目的 评价变应性鼻炎、哮喘患者血清中白细胞介素IL-4、IL-6、IL-8检测指标的意义。方法 检索策略:通过中国生物医学文献数据库(CBMdisc)、中文全文数据库全面检索国内已发表的相关文献。选择标准:中国成人变应性鼻炎、哮喘患者与对照组血清白细胞介素IL-4、IL-6、IL-8水平检测。资料收集和分析:由2位评价者按照上述检索策略收集文献。排除那些不符合选择标准要求的试验。结果 经Meta分析,发作期、缓解期变应性鼻炎患者血清中IL-4水平分别较对照组上升129.45 ng/mL(95％CI 124.95～133.96)、35.00 ng/mL(95％CI 32.01～39.78),有显著统计学意义(P<0.000 01):缓解期IL-6水平较对照组上升21.87 ng/mL(95％CI 19.83～23.91),有显著统计学意义(P<0.000 01);发作期、缓解期IL-8水平分别较对照组上升41.75 ng/mL(95％CI 29.14-54.36)、98.94 ng/mL(95％CI 96.48-101.41),有显著统计学意义(P<0.000 01);发作期IL-4水平较缓解期上升129.99 ng/mL(95％CI 125.00～134.99),有显著统计学意义(P<0.000 01)。结论 IL-4、IL-6和IL-8参与了变应性鼻炎、哮喘的发生和促进了变态反应性疾病的发展,有必要开展更广泛研究和更深层的原因探索。     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.     

Role of interleukin-17F in chronic inflammatory and allergic lung disease

IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case-control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.     

Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.     

肺表面活性蛋白A在皮质类固醇调节哮喘小鼠树突细胞共刺激分子表达中的作用

目的 研究皮质类固醇激素调节小鼠哮喘模型树突细胞表面共刺激分子表达的机制，以及肺表面活性蛋白A（SP-A）在其调节中的作用。方法 BALB/c小鼠30只，分为3组：哮喘组，采用卵蛋白（OVA）致敏和激发；对照组，以生理盐水代替OVA；治疗组，每次OVA激发后10min，腹腔注射地塞米松01mg。用免疫组化法检测SP-A在肺内的表达情况。采用Leica DM Snk软件进行图像采集，并用Qwin软件计算小气道内棕色区域面积，取平均值，进行统计分析。分离培养脾脏树突细胞，用流式细胞仪（FACS）检测树突细胞表面共刺激分子CD80的表达变化。结果 哮喘组肺组织表现为嗜酸性细胞及淋巴细胞浸润为主的炎症变化，治疗组和对照组无此变化。哮喘组的SP-A表达明显低于对照组和治疗组（P〈0．01），CD80的表达率明显高于治疗组（P〈0.01）；哮喘组小气道内SP-A表达与树突细胞CD80阳性率呈负相关（r=-0．907，P〈0．01）。结论 皮质类固醇对小鼠哮喘模型的肺表面活性蛋白有明显的保护作用，可通过激发肺表面活性蛋白抑制树突细胞表面共刺激分子CD80的表达。     

The effectiveness of intranasal corticosteroids in combined allergic rhinitis and asthma syndrome

Background Allergic rhinitis (AR) and asthma often coexist and may represent two manifestations of the same disease recently named combined AR and asthma syndrome (CARAS). Aim To review the common pathophysiology of combined AR and asthma and to investigate the efficacy of intranasal corticosteroids (INCS). Methods Medline was used to identify articles relevant to mechanisms. A Cochrane systematic review was performed to assess the efficacy of INCS in CARAS. Results There is cross‐talk, evidence of a common inflammatory response in both sites, linked by a systemic component. The efficacy of anti‐inflammatory INCS on asthma outcomes was assessed in a systematic review of 12 randomized controlled trials involving 425 subjects. After INCS there were non‐significant trends for improvement in asthma symptom score (standardized mean difference (SMD) of 0.61; P=0.07), forced expiratory volume in 1 s (SMD of 0.31; P=0.08), and morning peak expiratory flow (weighted mean difference of 36.51; P=0.06). There was no impact on methacholine airways responsiveness (SMD of ?0.20; P=0.4). The review identified two promising new treatment options in united airway disease such as INCS as monotherapy in rhinitis and mild asthma, and a combined intranasal and intrabronchial corticosteroid (IBCS) deposition technique. Conclusion Common mucosal inflammatory responses occur in CARAS. This systematic review shows trends for a benefit of INCS in CARAS, but recognizes that more research is needed. At this stage, the current best practice is to treat asthma conventionally with IBCS with or without β₂‐agonist and to add INCS to improve specific rhinitis symptoms.