1、 Prof.Prof.YiQiangYiQiang-Chen-Chen Asthma：a human killer!The musician Beethoven(1770-1827）a famous singer:LiJun-Deng1953-1995 Definition Clinical definition (from 1950s to 1970s)Allergic theory (from early of 1970s to the middle of 1980s)Difinition of chronic airway inflammation (from the latter of
2、 1980s to now)Definition Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role.The chronic inflammation causes an associated increase in airway hyperresponsiveness that leads to recurrent episodes of wheezing,breathlessness,chest tightness,and
3、 coughing,particularly at night or in the early morning.DefinitionThese episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment.Airway Airway RemodellingRemodelling may happen following may happen following prol
4、ongprolonged ed course ofcourse of the the disease disease.Chronic airway inflammation a essential quality of asthmaInflammation allergic eosinophile granulocyte infiltrationInhaled glucocorticoidInfection non-specificnon-specific neutrophil granulocyte infiltrationAntibiotics Inflammation Infection
5、 Epidemiology morbidity of asthmaasthma in the world:Asthma is one of the most common chronic diseases with an estimated 300 million individuals affected worldwide.million individuals affected worldwide.The prevalence of asthma is increasing in most countries.The prevalence rate of severe asthma in
6、the worlw ranges from 1%-30%.Morbidity of asthmaasthma In china:about 0.5%-5%Masoli M,et al.Allergy 2004.Morbidity of asthma in the worldMasoli M,et al.Allergy 2004.Mortality of asthmatics in the world 36.7 GINAGINAglobal initiative for asthma:the most important guideline for asthmaasthma prevention
7、 and treatment in the world.Published in 1995 Amended in 1998,2002,2005,20062006 The lastest,2012 The practice situation of GINA in China Only to some patients in some big and middle city.The percent of patients accepted the standard treatment of asthma is less than 5%.E Etiologytiology Unknown gene
8、tic factor environmental factor allergens Other diseases Drugs Emotional factors ExerciseMiteMoldPollenPetcockroachtobacco smokeclimateEnvironmental pollutantsOther factorsGastroesophageal reflux diseaseChronic sinusitis or rhinitisViral respiratory infectionsCoexisting respiratory infection Aspirin
9、 Nonsteroidal anti-inflammatory drugUse of beta-adrenergic receptor blockers pathogenesis Immunologic-Inflammation mechanism Airway Inflammation Airway hyperresponsiveness(AHR)Airway Remodelling Neuromechanism哮喘的发病机制Th2Ag mediaAMcytokineBLCBLCIgEIgE MC EOSairway edema mucus embolus mucus secretionde
10、squamation of the epitheliumsmooth muscle hyperplasiaET-1,TGF-AHRAHR pathogenesisallergyinflammationneuromechanismAHRAsthma哮喘的发病机制Th2AgAg 介质介质AM细胞因子细胞因子BLCBLCIgEIgE MC EOS血浆渗出水肿形成 粘 液 栓粘液分泌过多 血管扩张 新血管形成血浆渗出水肿形成 粘 液 栓粘液分泌过多 血管扩张 新血管形成上皮脱落上皮脱落神经末稍裸露神经末稍裸露胆碱胆碱能能神经神经亢进亢进+肾上肾上腺素腺素受体受体功功能能低低下下+NANC+NANC释放
11、释放神经介质神经介质失失衡衡平滑肌收缩平滑肌收缩 肥大肥大/增生增生ET-1,TGF-等AHRAHR气道气道免疫免疫炎症炎症气道高反应性气道高反应性气道重构气道重构神经神经调节调节机制机制哮喘哮喘 pathologydesquamation of the epitheliummononuclear cell and eosinophil infiltrationvasodilatationmucous glandhypertrophyedemamucusBasilemmathickeningsmooth muscle hyperplasia pathologyCross section of
12、a small airway(30/min30/minBreath soundsModerate wheezing at mid-to endexpirationLoud wheezes through-hout expirationLoud inspiratory expiratory wheezesLittle air movement without wheezesHeart rate(beats/min)120Relative bradycardiaPulsus paradoxus(mmHg)25Often absentMental statusMay be agitatedUsual
13、ly agitatedUsually agitatedConfused or drowsyFunctional assessmentPEF(pre/personal best)8050-8050 or response to therapy lasts2hours9591-9591606060PaCO2(room)422次/周肺功能（PEF或FEV1）正常正常预计值(或本人最佳值)的80%B.评估未来风险(急性发作风险，病情不稳定，肺功能迅速下降，药物不良反应)与未来不良事件风险增加的相关因素包括：临床控制不佳；过去一年频繁急性发作；曾因为严重哮喘而住院治疗；FEV1低；烟草暴露；高剂量的药物
14、治疗。Global Initiative for Asthma.Global strategy for asthma management and prevention.Updated 2011.Differential diagnosisLeft heart failure（Cardiac asthma）COPDUpper airway obstructionAllergic bronchopulmonary aspergillosis（ABPA）All that wheezes is not asthma!支气管哮喘与其他疾病鉴别要点支气管哮喘与其他疾病鉴别要点 哮喘哮喘左心衰左心衰慢支和
15、慢支和COPDCOPD呼吸困难 发作性、阵发性、呼气性阵发性、端坐喘息和劳力性其他症状 干咳、胸闷等心悸、粉红色泡沫痰慢性咳嗽、咳痰体征哮鸣音为主哮鸣音、广泛湿啰音干湿啰音并存病史过敏源接触、部分有家族史高血压或心脏病史长期吸烟、有害气体接触等影像学无特殊肺淤血、肺水肿、心影扩大肺纹理增多、粗乱；肺气肿征支气管扩张剂可迅速缓解无明显缓解有一定缓解其他其他支气管哮喘与其他疾病鉴别要点（续）支气管哮喘与其他疾病鉴别要点（续）上气道阻塞性病变上气道阻塞性病变ABPAABPA呼吸困难呼吸困难吸气性顽固性喘息其他症状其他症状根据阻塞原因不同而不同发热、金棕色胶胨样脓痰或血痰体征体征吸气性喘鸣哮鸣音、湿啰
16、音影像学影像学上气道异物、肿瘤表现游走性、一过性肺浸润阴影支气管扩张剂支气管扩张剂无明显缓解有一定缓解，但需加用抗真菌药物才能控制其他其他气管镜下可见异物、肿物外周血嗜酸性粒细胞增加；烟曲菌抗原皮内试验快速反应阳性；经纤支镜吸出物发现菌丝，反复培养有曲菌生长 Complication Pneumothorax bronchiectasis mediastinal emphysema interstitial pneumonia atelectasis pulmonary fibrosis chronic bronchitis pneumocardial disease emphysemaTre
17、atment Goals Avoid risk factors Medications exacerbation Persistent Desensitization:Immunotherapy for specific allergens education The goal of asthma care is to achieve and maintain control of clinical manifestation and prevent the future risk of the disease for prolonged period.Clinical control of
18、asthma is defined as:-No(twice or less/week)daytime symptoms-No limitations of daily activites,inlcuding exercise-No nocturnal symptoms or awakening because of asthma-No(twice or less/week)need for reliever treatment-Normal or near-normal lung function-No exacerbationsGoals MEDICATIONSQuick-relief m
19、edications Long-term control medicationsShort-acting 2-agonists(SABAs)short-acting anticholinergic agents（SAMA)short-acting theophyllineSystemic glucocorticosteroidsinhaled glucocorticosteroids(ICS)Long-acting Long-acting 2-2-agonists(agonists(LABAs)sustained-release theophyllineleukotriene modifier
20、disodium cromoglycatedecreased systemic glucocorticosteroidsAnti-IgEICS/LABAsInhaled 2-agonistsThe time of startThe time of lastQuicklyShort-acting long-actingsalbutamolformoterolterbutalineslowlySalmeterolAnti-cholinergic drug An anti-cholinergic effect of ipratropium bromide blocks the effect of t
21、he cholinergic nerves,causing the muscles to relax and the bronchi to dilate.When inhaled,ipratropium bromide goes directly to the airways,and very little is absorbed into the body.Short-acting:Ipratropium(SAMA)Long-acting:Tiotropium(LAMA)Theophylline It provides mild bronchodilation in asthmatics.T
22、his drug may also have anti-inflammatory properties,enhance mucociliary clearance,and strenghthen diaphragmatic contractility.The drug serum concentrations need to monitored closely owing to the drugs narrow toxic-therapeutic range,individual differences in metabolism,and the effects of many factors
23、 on drug absorption and metabolism.Aminophylline Aminophylline Sustained Release Tablets Anti-inflammatory agents GlucocorticosteroidsIt is the most potent and consistently effective anti-inflammatory agents currently available.They reduce both acute and chronic inflammation,resulting in fewer asthm
24、a symptoms,improvement in airflow,decreased airway hyperresponsiveness,fewer asthma exacerbations,and less airway remodeling.These agents may also potentiate the action of 2-agonists Anti-inflammatory agents GlucocorticosteroidsThe inhaled are preferred for the long-term control of asthma and are fi
25、rst-line agents for patients with persistent asthma.Beclomethasone Budesonide Fluticasone PropionateAnti-inflammaiotory agents Glucocorticosteroids The oraled:It is most effective in achieving prompt control of asthma exacerbations or severe persistent asthma.Prednisone PrednisoloneAnti-inflammaioto
26、ry agents Glucocorticosteroids ivdrip:it is mainly used to the severe exacerbations of asthma.Succinic acid-hydrocortisoneMethylprednisolone HexadecadrolAnti-inflammaiotory agents leukotriene modifiers decrease leukotriene production.It cause modest improvements in lung function and reductions in as
27、thma symptoms and lessen the need for 2-agonists rescue therapy.Zafirlukast MontelukastOther medicationsAntihistamine drug：KetotifenCombination：Budesonide and Formoterol Fumarate Powder for InhalationSalmeterol Xinafoate and Fluticasone Propionate Powder for InhalationTypes of drugaerosolsolutionpow
28、derTreatment of exacerbationSABA+Aminophylline（oral）+SAMA mildTreatment of exacerbation moderateSABA(inhaled）+SAMA or ICS(Suspension)Suspension)+AminophyllineAminophylline （IVorIVor ivdripivdrip)glucocorticosteroids（oral)+oxygenoxygen inhalation inhalationTreatment of exacerbation Severity2-agonists
29、（inhaled persistently）+SAMA or ICS(+SAMA or ICS(Suspension)Suspension)+AminophyllineAminophylline （IV or IV or ivdripivdrip)+glucocorticosteroids（iv to oral)Oxygen,fluid infusion,machine ventilationventilation and antibioticsTreatment of exacerbationTreatment of PersistentAsthma educationEnvironment
30、al controlAs needed rapidacting2-agonistAs needed rapid-acting 2-agonistControlleroptionsSelect oneSelect oneAdd one or moreAdd one or moreLow-dose inhaledICSLow-dose inhaledICS pluslong-acting b2-agonistMedium-or high-doseICS plus long-actingb2-agonistOral glucocorticosteroid(lowest dose)Leukotrien
31、emodifierMedium-orhigh-dose ICSLeukotrienemodifierAnti-IgEtreatmentLow-dose ICS plusleukotriene modifierSustained releasetheophyllineLow-dose ICS plussustained releasetheophyllineTreatment of PersistentLevels of control controlPartly controluncontroledSTEP1STEP2STEP3STEP4STEP5Step upStepdownStep upS
32、tep downTreatment actionMaitain and find lowest control ling stepConsider steping up to gain controlStep up untill controlled治治 疗疗以以哮喘哮喘临床控临床控制制为目标为目标的的哮喘哮喘循环治疗模式循环治疗模式哮喘控制哮喘哮喘控控制制哮喘哮喘控控制制慢性慢性疾疾病病都都有可有可供长供长期期监测监测病情的病情的简单简单有有效效的的管理工具管理工具血糖仪血糖糖尿病高血压血压血压计疾病指标工具？峰流速仪？ACT？哮喘PEF？ACT评分？ACTACT是一种经验证是一种经验证的，可的，可被医生被医生或患者或患者用于自我评估用于自我评估的，的，包括包括5 5个问题个问题的的简易问卷简易问卷educationAsthma can be controled!Thank You !
