卫生假说的免疫学机制在哮喘防治中的研究进展

哮喘的特征是慢性气道炎症和气道高反应性.目前对哮喘治疗的认识是"可以控制,但不能治愈".近年来,哮喘发病的"卫生假说"提出早期微生物的暴露可能对哮喘的发病起保护作用.传统的解释是微生物负荷增加可诱导免疫反应向Th1偏移.由于哮喘是由免疫耐受缺陷导致的疾病,因此诱导抗原特异性T细胞耐受可能是此假说的另一种解释,并有望因此为防治哮喘提供新的思路.     

过敏性支气管哮喘免疫发病机制的最新研究进展

过敏性支气管哮喘(简称哮喘)是一种由不同的辅助性T细胞亚型决定的慢性气道炎症性疾病.既往认为“Th2哮喘假说”是过敏性哮喘的主要发病机制,而越来越多的研究表明,除了Th2之外其他辅助性T细胞也参与了哮喘的发病机制,尤其是Th1和Th17细胞对于气道中性粒细胞型炎症的发展至关重要.抑制这些免疫细胞也许为过敏性哮喘的有效治疗提供了方向.     

哮喘与轴突反射

气道上皮构成一保护性屏障,哮喘时该屏障遭到破坏,可导致支气管的高反应性和哮喘的病理学特征。然而,上皮损伤与哮喘病理生理学特征之间的联系尚未确定。本文提出释放具有强力作用的感觉神经肽,经轴突反射引起哮喘发病的假说。若该假说成立,则可能对哮喘的治疗具有重要的意义。     

微生物暴露与支气管哮喘的关系

支气管哮喘（简称哮喘）尤其是儿童哮喘的发病率在全球范围有明显升高。而在农场长大的儿童哮喘发病率较低。哮喘发病率的升高与卫生条件改善、家庭规模缩小和微生物暴露尤其是个体早期微生物暴露机会减少有关,其降低了机体接受“免疫训练”的机会,即“卫生学说”,近期有学者建议改为“早期免疫刺激假说”。该文主要介绍早期微生物及微生物组分暴露与哮喘的关系的作用机制进展,早期微生物暴露可能是潜在的预防哮喘的新途径。     

老年支气管哮喘与肺部感染

支气管哮喘与感染的关系长期以来一直受到关注。一方面感染诱发气道高反应性，可能是哮喘发病或急性发作的重要诱因之一。另一方面是哮喘特别慢性哮喘患者气道纤毛粘液痰的清除功能削弱，容易导致病原微生物的定植，而在大剂量应用激素和激素依赖型哮喘因免疫抑制可能特别...     

细胞信号转导在Th细胞分化中的作用

支气管哮喘(哮喘)是由多种细胞(如嗜酸粒细胞、肥大细胞、T细胞、中性粒细胞、气道上皮细胞等)和细胞组分参与的气道慢性炎症性疾患[1]。气道高反应性和可逆性气流受限是其病理特征。目前研究表明:Th1和Th2之间平衡失调是哮喘发病的重要机制。并认为Th2优势应答是哮喘发病的始动因素和维持因素,而对Th1优势应答在哮喘中的作用意见尚未统一。Kavita[2]研究表明:STAT4介导的细胞信号转导对由变态反应原诱导的气道反应的加重起着重要作用,而且Th1优势应答诱导产生的对嗜酸性粒细胞有趋化功能的趋化因子可引起哮喘患者气道极大的损伤。因此…     

诱导痰检测技术在支气管哮喘中的应用进展

支气管哮喘(哮喘)的本质是一种慢性气道炎症,而诱导痰检测是一种可反映气道炎症的无创气道采样方法.诱导痰细胞学计数可广泛用于哮喘的诊断、分型及炎症的评估;诱导痰中细胞因子检测在哮喘的发病、病情评估、个体化治疗中有重要的作用;随着组学在国内外各项研究中的运用不断成熟,可对诱导痰成分进行组学分析,特别是转录组学与蛋白组学分析...     

地塞米松对支气管哮喘大鼠气道重塑及气道平滑肌中Toll样受体4表达的影响

气道炎症和气道重塑是支气管哮喘(简称哮喘)发生、发展的重要环节,但其发病机制尚未完全明确[1].Toll样受体(Toll like receptor,TLR)是天然免疫和获得性免疫的桥梁[2],研究结果表明,TLR在哮喘的发生、发展中可能起着较为重要的作用[3].地塞米松是治疗哮喘的经典药物,对哮喘的气道炎症和气道重塑均有改善作用,但其作用机制不明.因此,我们将建立哮喘动物模型,从整体水平探讨地塞米松治疗对哮喘气道重塑以及哮喘气道平滑肌中TLR4表达的影响.     

过氧化物酶体增殖物激活受体对哮喘患者树突状细胞免疫调控的影响

支气管哮喘是以Th1/Th2细胞比例失衡和Th2细胞优势分化为免疫学发病基础的慢性气道炎症性疾病。树突状细胞(DC)在哮喘发病中起重要作用,髓系DC(DC1)能促使支气管哮喘原始Th细胞向Th2细胞分化增殖,肺脏淋巴系DC(肺脏DC2)能诱导免疫耐受;过氧化物酶体增殖物激活受体-γ(PPAR-γ)能减轻哮喘气道炎症。因此,我们综述了PPAR-γ对哮喘患者DC免疫调控功能的影响,为哮喘的研究防治探索新思路。     

胰岛素抵抗与支气管哮喘的研究进展

支气管哮喘(简称哮喘)是由多种因素引起的异质性疾病,目前公认的发病机制之一是气道慢性炎症假说,但仍未完全明确.近来研究表明,胰岛素抵抗与哮喘发病机制密切相关.本文综述胰岛素及胰岛素受体、胰岛素信号通路、胰岛素抵抗相关细胞因子在哮喘发病中的作用机制,将有望在哮喘的治疗方面提出新的治疗方向和靶点.     

咳嗽变异性哮喘与气道重塑

咳嗽变异性哮喘（coughvariantasthma,CVA）是指以慢性咳嗽为主要或唯一症状的一种特殊类型哮喘,其病理生理改变与典型哮喘相同,若未及时诊治,约30％～40％可发展成为典型哮喘。气道炎细胞浸润和气道重塑是CVA的病理基础。CVA可称之为一种隐匿性哮喘,常被临床医师所忽略,患者失去正确的诊断与治疗。正确认识CVA的病理生理特征,对临床诊断和治疗具有重要的指导意义,可降低典型哮喘的发病率。本文就CVA与气道炎性反应和气道重塑的关系作一综述。     

Evaluation of blood vessels and edema in the airways of asthma patients: regulation with clarithromycin treatment

BACKGROUND: Although airway angiogenesis and edema have been proposed to contribute to the airway remodeling process in patients with asthma, there are few studies looking at these structural components in the airway tissue of asthma patients. Mycoplasma infection may be associated with chronic asthma and has been shown to induce angiogenesis and edema in a murine model. Participants and measurements: We evaluated blood vessels and edema by immunohistochemistry in endobronchial biopsy samples from 10 normal control subjects and 15 patients with mild-to-moderate asthma before and after a 6-week treatment with clarithromycin (n = 8) or placebo (n = 7). Type IV collagen and alpha(2)-macroglobulin were used to identify blood vessels and edema in the tissue, respectively. Mycoplasma pneumoniae was evaluated by polymerase chain reaction. SETTING: National Jewish Medical and Research Center. RESULTS: At baseline, the vascularity, the number of blood vessels, and the edematous area in the airway tissue were not significantly different between asthmatic patients and normal control subjects. However, asthmatic patients demonstrated increased blood vessel size compared with normal control subjects (p = 0.03). After clarithromycin treatment in asthmatic patients, the number of blood vessels was increased (p = 0.02), while edema decreased (p = 0.049). Asthmatic patients who tested positive for M pneumoniae showed a significant increase in vascularity than asthmatic patients who tested negative for M pneumoniae (p = 0.02). CONCLUSION: Our data suggest that angiogenesis and edema may not be significant features of airway remodeling in patients with chronic, mild-to-moderate asthma. Clarithromycin treatment in asthmatic patients could reduce the edematous area as identified by alpha(2)-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels.     

Irreversible airway obstruction in asthma

Asthma is generally characterized by fully reversible airway obstruction. However, a significant proportion of asthma patients demonstrate an incomplete reversibility of airway obstruction (IRAO) despite optimal treatment and the absence of a significant smoking history. Such partially irreversible airway obstruction may be due to residual airway inflammation, particularly of the eosinophilic type, and structural changes. Risks factors for IRAO include reduced pulmonary function early in life, frequent exacerbations, smoking, continuing exposure to a sensitizing agent, and adult-onset asthma. IRAO is associated with increased disease severity and increased asthma-related morbidity and mortality. Optimal asthma control, including prevention of asthma exacerbations, smoking avoidance, and sufficient anti-inflammatory therapy, should be implemented in an effort to avoid an accelerated decline in lung function and the development or worsening of IRAO.     

Occupational toluene diisocyanate (TDI) asthma--inhalation challenge test and TDI-HSA (human serum albumin) skin test and detection of specific IgE

Using a self-made bag inhalation challenge device. We diagnosed 12 TDI asthmatics, who were from 18 symptomatic workers. Of the 12 cases there were three types of airway reaction to TDI: three showed an immediate response; six, a late response; three, a dual response. After inhalation challenge, FEV1 PEFR, V50, and V25 descended obviously, suggesting that airway response to TDI in TDI asthmatics might occur in either larger or small airway. As a result of methacholine challenge nonspecific bronchial reactivity in 12 TDI asthmatics was markedly increased. After inhalation of TDI, the further descending of PC20 FEV1 showed that TDI could increase airway reaction to methacholine. Patients received skin test with TDI-HSA conjugate. There were positive response in 11 of the 12 TDI asthmatics and in 11 of the 62 TDI workers who had no symptoms after exposure to TDI, and no positive response in 18 common asthma patients. Therefore, TDI-HSA skin test can be used to a assist diagnosis of TDI asthma and a differential diagnosis from ordinary asthma. Specific IgE antibody levels showed no difference between TDI asthma and normal control group before TDI challenge. A marked increase in TDI asthma occurred after TDI challenge.     

儿童哮喘与气道重塑的研究进展

儿童支气管哮喘（简称哮喘）严重威胁儿童健康,其发病率在全世界范围内有增高趋势。气道炎症和气道重塑是哮喘的两个主要病理学特征,而气道重塑是影响哮喘疗效的重要因素之一。糖皮质激素是目前作用最强、应用最广泛的抗哮喘药物,也是目前预防气道重塑的首选药物。早期吸入激素及口服白三烯受体拮抗剂等可能有助于气道重塑的预防,但是不能逆转已形成的气道重塑,所以早期诊断及干预气道重塑的发生是儿童哮喘防治的关键。     

哮喘神经机制的研究进展

支气管哮喘（哮喘）是全球性的严重健康难题，发病机制错综复杂，至今仍不完全清楚。现在被较多学者接受的理论是气道慢性炎症学说、变态反应学说、气道高反应学说以及气道重构学说。其中气道慢性炎症、高反应性和气道重构均涉及到神经机制的参与。越来越多的研究发现神经机制在哮喘气道高反应性中起至关重要的作用，并与免疫机制相互作用，引起神经源性炎症反应。对神经机制的研究可能成为未来攻克哮喘难关的突破点。     

CpG-寡核苷酸与支气管哮喘

Th1／Th2失衡是支气管哮喘的重要免疫学发病机制,近年在支气管哮喘的发病机制中取得较大进展,CD4^＋T辅助细胞按其分泌的细胞因子不同分为Th1和Th2细胞,Th1反应可以抑制Th2反应,抑制气遭慢性炎症,含有未甲基化CpG结构的寡核苷酸是近年研究较多的一种调节Th1／Th2平衡的免疫制剂,本文就其调节Th1／Th2平衡在支气管哮喘治疗中的应用前景作一综述。     

Role of serum periostin in the management of asthma and its comorbidities

Type-2 airway inflammation is a major characteristic of asthma. Assessing its degree of severity is, therefore, essential in asthma management. Periostin, a matricellular protein belonging to the fasciclin family, is a key molecule linking type-2 airway inflammation and airway remodeling. Fortunately, periostin can be detected in the blood and used to provide sustaining airway information on type-2 inflammation and remodeling. Serum periostin is elevated in the eosinophilic/type 2 subtype of severe asthma, and its levels remain relatively stable and reflect genetic backgrounds. This suggests that serum periostin may serve as a marker of geno-endophenotype with type-2 airway inflammation and thus could be a predictive marker of the long-term prognosis of asthma under treatment. As expected, serum periostin is particularly elevated in comorbidities associated with the eosinophilic/type 2 subtype of severe asthma, including eosinophilic chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis. Conversely, serum periostin levels are relatively lower in the overweight/obese. Serum periostin measurements may help to significantly improve the management of patients with severe asthma.     

Relevance of Birth Cohorts to Assessment of Asthma Persistence

The definition of persistent asthma in longitudinal studies reflects symptoms reported at every assessment with no substantive asymptomatic periods. Early-childhood wheezing may be transient, especially if it is of viral etiology. Longitudinal studies provide greater opportunity to confirm the diagnosis by variability of symptoms, objective measurements, and therapeutic responses. Several clinical phenotypes of childhood asthma have been identified, with general consistency between cohorts. Persistent wheezing is often associated with loss of lung function, which is evident from early-childhood and related to persistent inflammation and airway hyperresponsiveness. Female sex, atopy, airway responsiveness, and personal smoking, but not exposure to environmental tobacco smoke, are risk factors for persistence of childhood asthma into adulthood. The effect of breastfeeding remains controversial, but gene–environment interactions may partly explain outcomes. Understanding the natural history and underlying causes of asthma may lead to development of strategies for primary prevention.     

Anti-inflammatory modulation of chronic airway inflammation in the murine house dust mite model

Asthma affects 300 million people worldwide and continues to be a major cause of morbidity and mortality. Disease relevant animal models of asthma are required for benchmarking of novel therapeutic mechanisms in comparison to established clinical approaches. We demonstrate that chronic exposure of mice to house dust mite (HDM) extract results in allergic airway inflammation, that can be significantly attenuated by therapeutic intervention with phosphodiesterase 4 inhibition and corticosteroid treatment. Female BALB/c mice were administered intranasally with HDM (Dermatophagoides pteronyssinus) extract daily for five weeks, and therapeutic intervention with anti-inflammatory treatment (dexamethasone 1 mg/kg subcutaneous once daily, prednisolone 10mg/kg orally twice daily, fluticasone 3, 10 and 30 microg intranasally twice daily, roflumilast 10 mg/kg orally twice daily and intranasally 10 and 30 microg twice daily) was initiated after three weeks of exposure. Chronic HDM extract exposure resulted in significant airway inflammation, demonstrated by bronchoalveolar lavage cell infiltration and lung tissue inflammatory gene expression by TaqMan low density array. Chronic steroid treatment significantly inhibited these parameters. In addition, roflumilast caused a significant reduction in airway inflammatory cell infiltration. We have demonstrated that chronic HDM-induced allergic inflammation can be significantly ameliorated by steroid treatment, and that phosphodiesterase 4 inhibition modulates inflammatory cell infiltration. Therefore, the murine HDM model may be a useful tool for evaluating new targets for the treatment of asthma.