2. 精准医学与支气管哮喘治疗

精准医学与支气管哮喘治疗,病因,治疗靶点,疾病亚分类,精准医学概念,精准医学在疾病诊断治疗中的应用,精准医学在疾病诊断治疗中的应用,支气管哮喘目前的治疗模式及现状,/pharmacology-treatment-of-asthma.,常用的支气管哮喘药物,Gina. 2016.,升阶梯治疗,支气管哮喘目前的治疗模式,目前治疗模式下存在的问题,以ICS为主的单独及联合LABA或LATRA的前三级治疗模式对大多数相应的患者达到了良好的控制目标；,但随后的升级疗法（4-5级）并未能取得良好的控制效果，这其中包括激素抵抗型患者。,这类患者消耗半数以上与哮喘相关的医疗保健支出，并且具有更高的哮喘相关死亡风险。,Godard P, Chanez P, Siraudin L, et al. European Respiratory Journal, 2001, 19(1): 61-67.,哮喘的严重程度与哮喘的医疗资源花费,导致目前这些问题的原因何在？,根据疾病控制的水平，给予以ICS为基石的抗炎治疗，而未考虑疾病的表型及内因型,哮喘发病机制中复杂的炎症网络,哮喘是一种异质性疾病,哮喘的表型分类没有与其发病机制紧密相结合,目前的治疗没有将药物选择与发病机制中优势型炎症机制相关联,哮喘表型的探索使哮喘有了粗略的外在分类,表型（Phenotype）、内因型（Endotype ）、基因型（Genotype ),哮喘的,哮喘表型（Phenotype）,表型，是指生物体的外在可见特征，是基因型和环境因素相互作用的临床表现结果；哮喘表型分类方法繁多： Clinical features which define phenotypes include: age of onset, triggers (allergens, viruses, exercise, cigarette smoke), atopic vs. nonatopic disease, natural history (epidemiologic phenotypes), symptom-based phenotypes (episodic vs. multitrigger), severity, exacerbation-prone, and response to therapy,过敏性哮喘、阿司匹林哮喘、职业性哮喘、运动性哮喘,触发因素分类,常见的哮喘表型分类,早发型晚发型,发病年龄,可根据如下指标分类：pattern of inflammation (eosinophilic, neutrophilic, paucigranulocytic), biomarkers (exhaled nitric oxide, eosinophilia, urinary leukotriene E4), bronchial hyper-responsiveness (BHR), and lung function.,哮喘内因型（Endotype）,哮喘的内因型分类是根据哮喘发病病理生理机制进行分类。,嗜酸粒细胞型哮喘中性粒细胞型哮喘混合粒细胞型哮喘寡粒细胞型哮喘,诱导痰细胞学分类,常见的内因型分类,表型与内因型的关系,一种表型可包含多种内因型；一种内因型可表现为多种表型。,表型与内因型的关系,哮喘的基因型（Genotype ）,根据基因的突变、异常、多态性对哮喘进行的疾病分类；这种分类理论上最精确，最能反映疾病的本质；但哮喘是一种多基因遗传疾病，临床实践中无法实施。,哮喘与基因多态性,走出哮喘治疗困境- 精准分类指导的治疗,从表型到内因型,基于发病机制，划分更细致、更准确、更精密！,Figure 1. Biomarker discovery and phenotyping in severe asthma: actuality and perspectives. FeNO:Fractional exhaled nitric oxide; FRC:Functional residual capacity; Gal-3:Galectin-3; IgE:Immunoglobulin E; RV:Residual volume; uLTE4:Urinary leukotriene E4.,Published in: Laura De Ferrari; Alessandra Chiappori; Diego Bagnasco; Anna Maria Riccio; Giovanni Passalacqua; Giorgio Walter Canonica; Expert Review of Respiratory Medicine 2016, 10, 29-38.DOI: 10.1586/17476348.2016.1111763Copyright 2015 Taylor & Francis,Emerging pediatric phenotypes/endotypes associated with response to asthma therapies,Moving towards precision care for childhood asthma. Mokhallati, Nadine; Guilbert, Theresa Current Opinion in Pediatrics. 28(3):331-338, June 2016.DOI: 10.1097/MOP.0000000000000361,Figure 2. The primary defined Th2-high and Th2-low severe asthma phenotypes. ICS: Inhaled corticosteroid.,Published in: Laura De Ferrari; Alessandra Chiappori; Diego Bagnasco; Anna Maria Riccio; Giovanni Passalacqua; Giorgio Walter Canonica; Expert Review of Respiratory Medicine 2016, 10, 29-38.DOI: 10.1586/17476348.2016.1111763Copyright 2015 Taylor & Francis,如何精准分类精准治疗？,Figure 3. Currently known aspects of asthma phenotypes. CXCR2:CXC chemokine receptor 2; FeNO:Fractional exhaled nitric oxide; Ig:Immunoglobulin; IL4R:Interleukin 4 receptor alpha; LT:Leukotriene.,Published in: Laura De Ferrari; Alessandra Chiappori; Diego Bagnasco; Anna Maria Riccio; Giovanni Passalacqua; Giorgio Walter Canonica; Expert Review of Respiratory Medicine 2016, 10, 29-38.DOI: 10.1586/17476348.2016.1111763Copyright 2015 Taylor & Francis,哮喘内因型精准医学面临的问题,1. 哮喘发病机制复杂，至今仍未完全明了，尚有更多的内因型亟