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1、Bronchial Asthma,Introduction,Bronchial asthmaa chronic inflammatory conditioninvolving a variety of cells including eosinophils,mast cells,T lymphocytes,neutrophils,and epithelial cells of the airway,as well as cellular elementswhich gives rise to the increase of airway hyper-reactivity.,Extensive
2、changeable and reversible ventilation restriction is commonCause recurrent tachypnea,feeling of out of breath,and coughing The symptoms are more usually present and aggravated at night or early in the morningRemission might be achieved spontaneously or following treatment,Epidemiology,160 million pa
3、tients in the worldprevalence：1%-5%，0.5-1%in chinaPrevalence in male is similar to that in femaleThe onset is before 12 years of age in the majorityFamily history could be found in 20%patientsRelated to allergic rhinitis,eczema and nasal polyp,Etiology,The pathogenesis of asthma is complicatedAffect
4、ed by genetics and the environmentIt is a multigene disorder and closely related to atopyMost patients have prior history of eczema,allergic rhinitis,food or drug allergy,and quite a few patients have family historyThe formation and attack of asthma is also a consequence of the function of multiple
5、environmental factors such as inhalation of allergens,respiratory tract virus infection,and coldness,Etiology,Genetic factors:multigene inheritance heritability 70-80%Predisposing factors:air pollution 1）inhalants：dust mites、pollen 2）infections 3）food 4）change of weather 5）mental factors 6）exercise
6、7）drugs 8）menstruation,pregnacy,Pathogenic mechanism,Asthma is Characteristic of hyper-reactivity of the airwayChronic（allergic）inflammation is the basic lesion of asthma,Allergic inflammation,Investigations have shown that allergic reactions like asthma are mediated by Th2 cells.There is an increas
7、e or predominance of Th2 or its cytokines.The resulting airway inflammation could be classified into the following two types:1.IgE mediated and T lymphocyte dependent pathway2.NonIgE mediated and T lymphocyte dependent pathway,Immunologic factorsThe role of IgE mediation,The combination of allergen
8、with specific IgE triggers the degranulation of the mast cells and eosinophils,resulting in release of mediators including leukotrienes C,D,E,and the subsequent smooth muscle contraction,edema of the mucosa,increase of secretion,and finally stenosis of the bronchioles,which all contribute to asthma.
9、Total serum IgE or specific serum IgE titer increase is seen in patients with asthma,indicating type I allergic reactions might be present.,nonIgE mediated,T lymphocyte dependent pathway,In delayed type allergic reaction,Th2 cell directly initiates imflammatory response by activation and agglutinati
10、on of various inflammatory cells via the release of multiple cytokines(IL-4、IL-13、IL-3、IL-5）,Neuromental factors,The complicated autonomic innervation of the bronchiopulmonary system includes cholinergic,adrenergic,nonadrenergic and noncholinergic nerves.-adrenergic receptor malfunction and the incr
11、eased tone of the vagus,or with simultaneous increase of-adrenergic reactivity,would promote contraction of the smooth muscle and secretion of the glands,resulting in attack of asthma,Endocrine factors,Asthma disappears in puberty in some patients;aggravated in menstruation period,during pregnancy,a
12、nd when there is hyperthyroidism,Hyper-reactivity of the airway,Bronchial reactivity refers to the contractive reaction of the airway to various stimuli including those chemical,physical or pharmacologic in nature,Pathology,The basic pathology of bronchial asthma includes imflammation and remodeling
13、 of the airway.The basic pathological change of the inflammmation includes infiltration of mast cells,macrophages,eosinophils,lymphocytes and neutrophils;edema of the submucosa,increase of the permeability of the microvasculature,retention of the secretion within the bronchioles,spasm of the bronchi
14、al smooth muscle,detachment of the cilated epithelium,exposure of the basal membrane,poliferation of goblet cells and increase of bronchial secretion,which contribute to form the chronic eosinophilic bronchitis,Clinical manifestation,The typical onset of asthma is accompanied by sneezing,nasal secre
15、tion,coughing and out of breath.If timely treatment is not given,the bronchial narrowing might get worse and cause dsypnea.In severe cases,the patient is obliged to take the sitting position which is refered to as othopnea,coughing with or without large amount of white foamy sputum,or even with cyan
16、osis.,Clinical manifestation,Physical examination:Increased anteroposterior diameter of the chest,over-resonance on percussion,wheezing all over the chest;when severe dyspnea exists,both breathing sounds and wheezing could be reduced or absent.No symptoms and signs might be present during the interv
17、al of attack,in some cases,wheezing could be noted on exersion,Clincal manifestation,Symptoms are more severe at night,and could be relieved after medication or spontaneously.When severe acute asthma attack could not be mitigated within 24 hours by appropriate use of adrenomimetics,the patient is in
18、 the state of persistent asthma.The patient might be struggling due to dyspnea before he becomes weak and unable to cough.Blood pressure might decline,cyanosis might appear,and the patient might even die from acute respiratory failure.,Lab,Peripheral blood：eosinophils increase.A false white cell cou
19、nt increase might occur if adrenaline is used.X-ray：over-inflation of the lung;increased lung markings;small area shadow might appear along the bronhchioles if there is bronchial pneumonitis or atelectasis,Lab,Lung function test：decrease of airflow rate and tidal volume,increase of reserve volume.Bl
20、ood gas test shows a decrease in PaO2;an initial PaCO2 decline may be noted and an elevation follows with progression.pH decreases in the late stage.during the interval of attack,lung function is usually normal except the reserve volume is increased.Daily test of PEF and its variance is helpful for
21、the judgement of the existence of subclinical asthma.,Lab,The suspected antigen is used for skin test so as to find out the allergen.The skin prick test is quite reliable,diagnosis,Diagnostic criteria for asthmaCriteria for cough variant asthma,Diagnotic criteria,1.recurrent breathlessness,wheezing,
22、coughing,and tightness in the chest.Usually related to contact of allergen,cold air,physical or chemical stimuli,upper respiratory tract infection with virus,and exercise,ect.2.diffuse or scattered expiratory wheezing could be heard during the attack,the expiratory phase is lengthened.3.the abve sym
23、ptoms and signs might be remitted after treatment or spontaneously.4.other causes of wheezing,short of breath,coughing and tightness in the chest are excluded.5.at least one of the following tests is positive,if the clinincal picture is（eg no wheezing or signs）：positive bronchial or exercise challen
24、ge testpositive bronchodilatator testFEV1 increase by more than 15%，and the increase of absolute FEV1 volume200ml；daily PEF variance or 24 hour fluctuation20%。when14or4、5 are met，bronchial asthma is diagnosed。,Differential diagnosis,1.Cardiac asthma Aminophylline,morphine,epinephrine2.asthmatic chro
25、nic bronchitis3.Bronchiogenic lung cancer4.eosinophilic lung diseases,Criteria for cough variant asthma,Also named allergic coughing,which is a potential insidious form of asthma and occurs at all age group.Its exclusive symptom is chronic coughing with no positive signs.Therefore it might be misdia
26、gnosed as bronchitis.However it is believed by most physicians that its mechanism of pathogenesis is identical to that of asthma,and treatment is effective when medications for asthma are indicated.,Criteria for cough variant asthma,Recurrent or persistent coughing for more than 2 months without muc
27、h sputum,which occurs at night or in the early morning,and got worse after exercise.No infection is present or long term use of antibiotics proves not effective.Bronchodilatators could reduce coughing（basic criterium）History of allergy or familial allergy，airway is high responsive,positive allergen
28、skin prick test,Staging,Asthma could be classified into the following 3 stages according to its clinical picture:exacerbation phase,persistent phase,and remission phase.,Evaluation of non-exacerbation phase,severe：frequent attack of symptoms,limited capability,bad sleeping,PEF or FEV60 of predicted,
29、PEF varience30moderate：daily attacked,sleeping and ability compromised,nocturnal asthmaonce a week,PEF or FEV150，30,Evaluation of non-exacerbation phase,minor：symptomsonce a week，but less than once a day.ability and sleeping might be affected.nocturnal asthmatwice a month，PEF or FEV180，PEFR 2030inte
30、rmittent：symptoms appear intermittently,once a week,short duration of attack（hoursdays）,nocturnal asthmatwice amonth，pulmonary function is normal，PEF or FEV180，PEFR20,Evaluation of the severity for acute attack,Clinical feature minormoderate severe breathlessness walkingmoving restposition supine si
31、tting bending forwardspeech sentencephrases words unable to speakirritation possibleoften often sleepiness confusionsweatingyesyessignificant,Evaluation of the severity for acute attack,Clinical feature minor moderate severe acute sleep apneaBreath ratesomewhat quickened markedly apneaMotion ofacces
32、sory respiatory no frequent frequent paradoxical muscles and movement of the three depressions chest and abdomenSignWheezing sound scattereddiffuse diffuse weakened or absentPulse rate 120 120 or pulse rate（12岁）slowed，irregular,Clinical feature minor moderate severe acute sleep apnea PaCO26possible
33、respiratory failure（kPa）SaO2959195 90()pHdecline,Evaluation of the severity for acute attack,Goal of management for asthma,to effectively control acute attack and maintain minimal symtoms or no symptomsto prevent aggravation；to keep lung function around normal level；to maintain the ability to exerci
34、ce；to avoid the adverse reaction of the medications for asthma.,Standards for asthma control,minimal(or no)chronic symptoms,including symptoms at night.minimal times of asthma attack；no emergency room visit due to asthmaminimal use of 2 antagnists；no limitation of ability(including exercise).（6）24 h
35、our PEF variance20；(7)PEF normal or almost normal；(8)minimal adverse reactions of medications,Elimination of etiology,Avoid allergen,appropriate treatment of infection,eradicate exposure to the predisposing factors(smoking,paint,icecream,abrupt change of weather),Asthma:Prevention,Stop smokingDecrea
36、se ETS exposureReduce exposure to biological dustReduce exposure to pollutionReduce risk to respiratory virusesDietary:Increase antioxidants and Omega 3sDecrease exposure to cows milk,dairy,nuts,soy,wheat in infancy,Asthma:Treatment,Remove the allergenDrug TherapyBronchodilators(For acute responses)
37、Adrenocorticol hormone:dangerous side effects if used long termPsychosocial TechniquesStress ManagementSocial Support,Whats New for Treating Asthma?,Medications:long term or controller medicationsquick relief medicationsStepped therapy:start high,back downAsthma monitoring and action plansEnvironmen
38、tal controls,Overview of Medications,Controller medicationscontrol inflammationlong duration bronchodilationmultiple new medicationsQuick relief medicationsfor intermittent or breakthrough symptomsControversy:Use worsens asthma?Marker of worsening asthma?,Controller Agents,Inhaled corticosteroidsSys
39、temic corticosteroidsLong acting 2 agonistsCromolyn and derivativesMethylxanthinesLeukotriene Modifiers,Inhaled Corticosteroids,Control airway inflammation locallyIdeal:control asthma(high local potency);no side effects(low systemic effects)fluticasone,budesonide beclomethasone(triamcinolone,fluniso
40、lide),Systemic Corticosteroids,May be needed initiallySide effect profile well knownStep down therapyAlternatives:high dose inhaled corticosteroids;methotrexate;other immunosuppressive drugs,Long acting 2 Agonists,Salmeterolformoterol,Quick Relief Medications,2 AgonistsAnticholinergicsSystemic corti
41、costeroids,Managing Asthma Long term,Prevent symptomsMaintain normal pulmonary functionMaintain normal activity levelsPrevent exacerbations,emergenciesOptimize medical therapyPatient satisfaction(compliance),Methylxanthines(Theophylline),Used for over 50 years to treat asthmaPoorly understood mechan
42、ism of actionPhysiologic effects thought to include bronchodilation,stimulation of diaphragmatic contractility,mucocilliary clearance,and possibly some anti-inflammatory effect.Dose related toxicities include nausea,vomiting,headache,CNS stimulation,seizure,hematemasis,hyperglycemia,and hypokalemia,
43、Ipratropium Bromide,A synthetic anticholinergic compoundAnticholinergic compounds are known to cause bronchodilationAtropine has been used,but often limited due to side effects such as tachycardia,dry mouth,disturbances of visual accommodation,etc.Ipratropium thought to be relatively free of side effects,but with preservation of bronchodilatory properties,
