1、精準醫學與支氣管哮喘治療基因測序蛋白質組學生物大數據分析鑒定驗證應用病因治療靶點疾病亞分類精確診斷精確治療精準醫學概念精準醫學在疾病診斷治療中的應用疾病類別疾病名稱生物標志物干預腫瘤慢性粒細胞白血病BCR-ABL伊馬替尼肺癌EGFR吉非替尼/厄洛替尼黑色素瘤/甲狀腺癌BRAF V600E曲美替尼乳腺癌HER2曲妥珠單抗結腸癌/胰腺癌HER-1西妥昔單抗結直腸癌VEGFR-A貝伐單抗彌漫性大B細胞淋巴瘤CD20+利妥昔單抗精準醫學在疾病診斷治療中的應用類別疾病名稱生物標志物干預心血管疾病冠狀動脈疾病CYP2C19氯吡格雷精神疾病酒精利用障礙GRIK1托吡酯傳染病HIV/AIDSHIV病毒載量、C

2、D4+T細胞雞尾酒療法眼科疾病先天性黑朦RPE65基因治療肝臟疾病乙型肝炎HBV病毒載量核苷類似物、干擾素肺病囊性纖維化G551D依伐卡托藥物基因組學戒煙CYP2A6伐尼克蘭支氣管哮喘目前的治療模式及現狀/pharmacology-treatment-of-asthma.常用的支氣管哮喘藥物Gina. 2016.升階梯治療支氣管哮喘目前的治療模式目前治療模式下存在的問題以ICS為主的單獨及聯合LABA或LATRA的前三級治療模式對大多數相應的患者達到了良好的控制目標；但隨后的升級療法（4-5級）并未能取得良好的控制效果，這其中包括激素抵抗型患者。這類患者消耗半數以上與哮喘相關的醫療保健支出，并

3、且具有更高的哮喘相關死亡風險。Godard P, Chanez P, Siraudin L, et al. European Respiratory Journal, 2001, 19(1): 61-67. 哮喘的嚴重程度與哮喘的醫療資源花費導致目前這些問題的原因何在？根據疾病控制的水平，給予以ICS為基石的抗炎治療，而未考慮疾病的表型及內因型哮喘發病機制中復雜的炎癥網絡哮喘是一種異質性疾病哮喘的表型分類沒有與其發病機制緊密相結合目前的治療沒有將藥物選擇與發病機制中優勢型炎癥機制相關聯哮喘表型的探索使哮喘有了粗略的外在分類表型（Phenotype）、內因型（Endotype ）、基因型（Gen

4、otype )哮喘的哮喘表型（Phenotype）表型，是指生物體的外在可見特征，是基因型和環境因素相互作用的臨床表現結果；哮喘表型分類方法繁多： 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 (epi

5、sodic vs. multitrigger), severity, exacerbation-prone, and response to therapy過敏性哮喘、阿司匹林哮喘、職業性哮喘、運動性哮喘觸發因素分類常見的哮喘表型分類早發型晚發型發病年齡可根據如下指標分類：pattern of inflammation (eosinophilic, neutrophilic, paucigranulocytic), biomarkers (exhaled nitric oxide, eosinophilia, urinary leukotriene E4), bronchial hyper-r

6、esponsiveness (BHR), and lung function. 哮喘內因型（Endotype）哮喘的內因型分類是根據哮喘發病病理生理機制進行分類。嗜酸粒細胞型哮喘中性粒細胞型哮喘混合粒細胞型哮喘寡粒細胞型哮喘誘導痰細胞學分類常見的內因型分類表型與內因型的關系一種表型可包含多種內因型；一種內因型可表現為多種表型。表型與內因型的關系哮喘的基因型（Genotype ）根據基因的突變、異常、多態性對哮喘進行的疾病分類；這種分類理論上最精確，最能反映疾病的本質；但哮喘是一種多基因遺傳疾病，臨床實踐中無法實施。哮喘與基因多態性走出哮喘治療困境- 精準分類指導的治療從表型到內因型基于發病機制

7、，劃分更細致、更準確、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;

8、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 & FrancisEmerging pediatric phenotypes/endotypes associated with response to asthma th

9、erapiesMoving towards precision care for childhood asthma. Mokhallati, Nadine; Guilbert, Theresa Current Opinion in Pediatrics. 28(3):331-338, June 2016.DOI: 10.1097/MOP.0000000000000361Figure 2. The primary defined Th2-high and Th2-low severe asthma phenotypes. ICS: Inhaled corticosteroid.Published

10、 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如何精準分類精準治療？Figure 3. Currently known aspects of asthma

11、 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哮喘內因型精準醫學面臨的問題1. 哮喘發病機制復雜，至今仍