-英文教学讲解课件ChronicObstruct.ppt

1、Chronic Obstructive Pulmonary Diseaseand Asthma UpdateJohn L.Faul,MD FCCPAssistant Professor,Division of Pulmonary/Critical Care MedicineStanford UniversityCOPD:Outline1.Epidemiology2.Definitions3.Medical management 4.Hypoxia5.Infections6.Vaccination Universal Problem COPD:epidemiology14 million in

2、the US with COPD12.5 million with chronic bronchitis1.65 million with emphysema4th leading cause of death in US3rd most frequent diagnosis of patients receiving home carePrevalence of COPD in the US*Age-adjusted to 2000 US population.Represents a statistically significant difference from rate among

3、males.Mannino et al.MMWR.2002;51(SS-6):1-16.Rate/1,000 Population*020304050607080901980198219841986YearMaleFemaleTotal101988199019921994199619982000 Since 1987,the prevalence of COPD among women has been significantly higher than that among menCOPD:The Usual SuspectsCOPD:risk factorstobacco smoking

4、accounts for 80-90%of the risk of developing COPDage of starting,total pack-years and current smoking status are predictive of mortalityonly 15%of smokers develop clinically significant COPDalpha1-antitrypsin deficiency(accounts for less than 1%of all COPD cases)occupational exposures to dusts and f

5、umesLung function declines with ageElastic tissue is lost in emphysemaCOPD:definitionsChronic bronchitis-a clinical definition:“the presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded”Emphysema-a pathol

6、ogic definition:“abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls”Pink puffers&Blue bloatersCOPD:HyperinflationIncreased retrosternal airspaceFlatdiaphragmsIncreasedAP diameterCOPDCOPD:Oxygen therapyOxygen therapy in COPD:ex

7、tends life in hypoxemic patientsNOTT trial,Ann Int Med 1980;93:391-398MRC trial,Lancet 1981;1:681-685strengthens cardiac function,improves exercise performance and ADLswhen FEV1 1.0 L(or 50%predicted)anABG should be doneHome O2 costs in the US/yr:$2,400,000,000 Oxygen Dissociation Curve1008060Below

8、PaO2=60mmHg,Hemoglobin rapidly loses oxygen carrying capacity(West:Textbook of Physiology)HemoglobinSaturation%40 60 80_40_20 0iiiAt 80mmHg,95%satAt 60mmHg,90%satAt 40mmHg,70%satPaO2(mmHg)Hypoxic Pulmonary VasoconstrictionuThe lung regulates blood flow according to its oxygen contentuA low venous ox

9、ygen content(low oxygen content in the pulmonary artery)prevents blood flow to the lungBloodFlow%Air sack(Alveolar)OxygenWest:Textbook of PhysiologyOxygen-sensitive chemoreceptors located in the pulmonary arteriole are the dominant controllers of pulmonary vascular toneFishman AP:Hypoxia on the pulm

10、onary circulation.How and where it acts.Circ Res 1976;38:221231COPD:a case in pointCC:Mrs.H.is a 67 y.o female with worsening dyspnea x several years who presents for 2nd opinion regarding diagnoses,and management,of her“breathing problem”her past diagnoses have includedasthma,bronchitis,and emphyse

11、mashe wants to know exactly what she has.COPD:a case in pointHer dyspnea is much worse in the last year,to the point that she can no longer bathe or cook without help.She has an occasional cough,productive of scant sputum.She smoked 2 ppd x 40 years but quit 6 years ago.COPD:a case in pointShe takes

12、 the following medications:albuterol MDI 2-4 puffs QID and prnthis is her“favorite”medicineatrovent MDI 2 puffs QIDshes not sure this one helps,but maybetheophylline 200 mg BIDsome doctor gave her this“years ago”prednisone 10 mg QD continuously for 3 years with occasional increasesshes never taken a

13、ny estrogen replacementCOPD:a case in pointShes takes antibiotics 6-7 times/year when her breathing“gets really bad”Shes been on oxygen but doesnt like itShes too short of breath to do any exerciseShe has been in the hospital 4 times in the last year and was intubated once,6 months agoHPI:Exacerbati

14、on of COPDAnthonisen et al,Ann Int Med 1987;106:196Saint et al,JAMA 1995;273(12):957If 2 of 3 following criteria are met:increasing dyspneaincreased sputum volumeincreased sputum purulenceExacerbation of COPDNon infectious and infectiousInfections include viralControversial if all sputum cultures ar

15、e causativeFor patients with 2 or especially 3 cardinal features,antibiotics are usefulShort courses of antibiotics are usefulAmsden GW et al.,Chest 2003:123:772-777Antimicrobial TherapyOral agents used earlier in therapyMonotherapy used whenever possiblePatient compliance(once-daily dosing)Comprehe

16、nsive disease managementVaccinations and COPDAnnual influenza vaccine:Reductions in exacerbation rates particularly within 3 weeks.No evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Pneumococcal vaccine every 5 yearsNo evidence t

17、hat pneumococcal vaccine reduces the severity of COPDPoole PJ.Cochrane Database Syst Rev.2000;(4):CD002733.Leech JA.CMAJ.1987:136(4):361-5.COPD:oral steroids for ER dischargesAaron SD.N Engl J Med.2003;348(26):2618-25.%relapse freeDayn=147,Pred 40/day for 10 days*Vlad the InhalerCOPD:inhaled steroid

18、s and LABACalverley P.Lancet.2003 Feb 8;361(9356):449-56 Change In FEV1(ml)n=1465*Peak Flow RatesTiotropium versus Salmeterol Donohue JF Chest 2002.122:47-55.COPD:smoking cessationTobacco smoking is the most important factor in COPD,and stopping smoking is the only intervention known to modify the n

19、atural history of airways obstruction.COPD:smoking cessation%abstinence*Tonstad S.Eur Heart J.2003 May;24(10):946-55.COPD:advanced therapiesBullectomyLung volume reduction surgery(LVRS)TransplantationSurgery for emphysema:GOLD 03 Classification of COPDStage Characteristics 0:At Risk normal spirometr

20、y chronic sx(cough,sputum)I:Mild COPD FEV1/FVC 70%(for stages I-IV)FEV1 80%predicted with or w/o chronic symptoms II:Moderate COPD 50%FEV1 80%predicted with or w/o chronic symptoms III:Severe COPD 30%FEV1 50%predicted with or w/o chronic symptoms IV:Very severe COPD 30%FEV1 predicted or 50%pred plus

21、 chronic respiratory failure*respiratory failure:PaO2 50 mm HgTherapy at Each Stage of COPD 0:At Risk I*:Mild II*:Moderate III*:Severe IV*:Very Severe FEV1 Normal spirometry 80%predicted 80%&50%50%&30%30%Avoidance of risk factor(s);influenza vaccination Add short-acting bronchodilators when needed A

22、dd regular Rx c 1 long-acting bronchodilator.Add rehabilitation Add ICS if repeated exacerbations Add O2 Consider surgery Gold Update 2003*FEV1/FVC 70%COPD:managementStop smokingLong-term oxygenInhaled steroids and long-acting beta agonistsDiet and exerciseTreat acute exacerbationsMonitor lung funct

23、ionVaccinateAsthma Facts in the United StatesuAnnual number of hospitalizations:478,000uAnnual number of deaths from asthma:4,657uAnnual number of work days lost:14.5 millionuAnnual number of school days lost:14 millionuEstimated direct and indirect medical costs:$16 billion(needs validation)Morb Mo

24、rtal Wkly Rep.2002 March 29;51:1-13.Smooth Muscle DysfunctionAirwayInflammation Inflammatory Cell Activation Mucosal Edema Proliferation Epithelial Damage B.Membrane Thickening Bronchoconstriction Bronchial Hyperreactivity Hypertrophy HyperplasiaSymptoms/ExacerbationsAsthma PathophysiologyFlow(l/s)V

25、ol(l)-20-41324521345-6Pre-albuterolPost-albuterolPredictedSpirometryEosinophils in Human BronchiChanges in EG2 during FP therapyFaul JL,Thorax 1998.53,753-61Change in Mean Peak Flow with therapyHaahtela T.N Engl J Med 1994,331:700Change in Mean Peak Flow with therapyGreening AP.Lancet 1994,344:219-2

26、4Study DayProbability of Remainingin the Study1.00.80.60.40.2Sal/FP 100/50FP 100Salmeterol 50Placebo*3%071421283542495663707711%35%49%Comparison of Asthma TherapiesKavuru M et al.J Allergy Clin Immunol.2000;105:1108-1116.Time to First Exacerbation*1009590858075024681012141618202224Time to First Exac

27、erbation(weeks)Exacerbation-FreePatients(%)FP 88 mcg b.i.d.+Salmeterol FP 220 mcg b.i.d.Matz J et al.J Allergy Clin Immunol.2000;105:162S.Kavuru et al.J Allergy Clin Immunol.2000;105:1108-1116.Data on file,Glaxo Wellcome Inc.WeekMean Change from Baselinein FEV1(%)302520151050024681012Endpoint15%0.28

28、L5%0.11L2%0.01LSal/FP 100/50FP 100Salmeterol 50Placebo25%0.51L*P 0.008 vs FP 100,salmeterol 50,and placebo at endpoint.Doses in mcg b.i.d.Patients Treated With ADVAIR Diskus 100/50 had a Significantly Greater Improvement in FEV1Noonan et al.Am J Respir Crit Care Med.1999;159(3):640.Reiss et al.Arch

29、Intern Med.1998;158:1213-1220.FEV1(%Change from Baseline;Mean SE)Study Weeks(Postrandomization)302520151050-5036912151923313947526068768492 100 108 116 124 132 140Cumulative ExtensionPlaceboMontelukastBeclomethasonePrimary StudyPatients(15 Years)Not Controlled on PRN Beta-Agonists Improved FEV1(Stud

30、y 1 and Extension)Proportionof PatientsWithoutAsthma AttackDays Since RandomizationBeclomethasone(n=248)Montelukast(n=379)Placebo(n=253)P=0.006 Montelukast vs placeboP=0.001 Beclomethasone vs placeboP=0.129 Montelukast vs beclomethasone10.950.900.850.800.750.700102030405060708090Patients(15 Years)No

31、t Controlled on PRN Beta-Agonists Malmstrom et al.Ann Intern Med.1999;130:487-495.In this study,all patients benefited from mandatory use of spacers,enforced compliance,and rigorous monitoring of patientsAnti-IgE Asthma Therapies ruhMAb E-25*NS*Milgrom H.N Engl J Med.1999 23;341(26):1966-73.SxASTHMA

32、:a case in pointCC:Ms.B.is a 22 y.o female with episodic dyspnea x 2 years who presents for 2nd opinion regarding diagnoses,and management,of her“breathing problem”her past diagnoses have includedasthma,bronchitis,and allergiesshe wants to know exactly what she has.ASTHMA:a case in pointHer dyspnea

33、is much worse in the last year,to the point that she occasionally has to skip class and once she has had to go to the ED.She has an occasional cough,productive of green sputum.She never smoked she is allergic to pollen and cats.Shes a Stanford student who eats a“healthy diet and takes lots of vitami

34、ns”A case in pointShe takes the following medications:albuterol MDI 2-4 puffs QID and prnthis is her“favorite”medicineprednisone 10 mg QD she is just finishing a steroid taper that was prescribed after her most recent Emergency Room visitshes never taken any steroid inhaler,because they dont work an

35、d shes fearful of their adverse effectsCOPD:a case in pointShes takes antibiotics 5 times/year when her breathing“gets really bad”She sometimes wheezes after exerciseShe has been in the ED 4 times in her lifetime,was admitted once,but has not been intubatedHPI:Considerations in Asthma Therapy1.Effic

36、acy2.Convenience3.Control4.Adverse effectsAdverse effects of Asthma Therapy1.Beta agonists:tremor,tachycardia2.Inhaled steroids:Voice,Bones,?Metabolic3.LKRAs:Headache4.Prednisone:Cushings syndrome012340130135140145140145150012346.56.05.55.04.50.0Time(yrs)Time(yrs)Standing Height(cm)Standing-height V

37、elocity(cm/yr)N Engl J Med 2000;343:1054-63.BudesonideNedocromilPlaceboBudesonideNedocromilPlaceboLong-Term Effects of Budesonide or Nedocromil in Children with AsthmaThe Rule of Twos(Who Needs Controller Therapy)Two beta-agonist canisters/yearTwo doses of beta-agonist/weekTwo nocturnal awakenings/m

38、onthTwo unscheduled visits/yearTwo prednisone bursts/year2002 NAEPP GUIDLINESSTEP 1:Mild Intermittent Asthma Symptoms Present 2days/week Brief Exacerbations Nighttime Symptoms 80%predicted PEF variability 2x/week but 2x/month FEV1 and PEF 80%predicted PEF variability 20-30%Daily low-dose inhaled cor

39、ticosteroidsOR Leukotriene modifier,theophylline2002 NAEPP GUIDELINESStep 3:Moderate Persistent Asthma Symptoms daily Exacerbations affect activity Nighttime symptoms 1x/week FEV1 and PEF 60-80%predicted PEF variability 30%Low-medium dose inhaled corticosteroids with long-acting Beta agonist OR Leukotriene modifier,theophylline2002 NAEPP GUIDELINESStep 4:Severe Persistent Asthma Continual Symptoms Exacerbations affect activity Nighttime symptoms frequent FEV1 and PEF 30%High-dose inhaled corticosteroidsAnd Long-acting beta agonistAND oral corticosteroids(2mg/kg/day)