1、Chronic Obstructive Pulmonary Diseaseand Asthma UpdateJohn L.Faul,MD FCCPAssistant Professor,Division of Pulmonary/Critical Care MedicineStanford University.COPD:OutlineuEpidemiologyuDefinitionsuMedical management uHypoxiauInfectionsuVaccinationu.Universal Problem.COPD:epidemiology14 million in the
2、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 care.Prevalence of COPD in the US*Age-adjusted to 2000 US population.Represents a statistically significant difference from rate among mal
3、es.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 men.COPD:The Usual Suspects.COPD:risk factorstobacco smoking a
4、ccounts 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 fu
5、mes.Lung function declines with age.Elastic tissue is lost in emphysema.COPD: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 path
6、ologic definition:“abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls”.Pink puffers&Blue bloaters.COPD:HyperinflationIncreased retrosternal airspaceFlatdiaphragmsIncreasedAP diameter.COPD.COPD:Oxygen therapyOxygen therapy in C
7、OPD:extends 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 Curve100806
8、0Below 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 v
9、enous oxygen 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
10、the pulmonary circulation.How and where it acts.Circ Res 1976;38:221231.COPD: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,an
11、d emphysemashe 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 point
12、She takes 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 neve
13、r taken any estrogen replacement.COPD: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:
14、.Exacerbation 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 purulence.Exacerbation of COPDNon infectious and infectiousInfections include viralControversial if all sputum
15、 cultures are causativeFor patients with 2 or especially 3 cardinal features,antibiotics are usefulShort courses of antibiotics are usefulAmsden GW et al.,Chest 2003:123:772-777.Antimicrobial TherapyOral agents used earlier in therapyMonotherapy used whenever possiblePatient compliance(once-daily do
16、sing)Comprehensive disease management.Vaccinations 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 year
17、sNo evidence that 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 Inhaler.COPD
18、:inhaled steroids 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 know
19、n to modify the natural 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 Ris
20、k normal spirometry 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 predict
21、ed or 50%pred plus chronic respiratory failure*respiratory failure:PaO2 50 mm Hg.Therapy 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 bronchodil
22、ators when needed Add 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 exacerbatio
23、nsMonitor lung functionVaccinate.Asthma 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(nee
24、ds validation)Morb Mortal 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 Path
25、ophysiology.Flow(l/s)Vol(l)-20-41324521345-6Pre-albuterolPost-albuterolPredictedSpirometry.Eosinophils in Human Bronchi.Changes in EG2 during FP therapyFaul JL,Thorax 1998.53,753-61.Change in Mean Peak Flow with therapyHaahtela T.N Engl J Med 1994,331:700.Change in Mean Peak Flow with therapyGreenin
26、g AP.Lancet 1994,344:219-24.Study 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*1009590858075024681012141
27、618202224Time to First Exacerbation(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(%)302520151
28、050024681012Endpoint15%0.28L5%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 FEV1.Noonan et al.Am J Respir Crit Care Med.1999;
29、159(3):640.Reiss et al.Arch 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
30、-Agonists Improved FEV1(Study 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 beclomethasone10.950.900.850.800.750.700102030405
31、060708090Patients(15 Years)Not 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 patients.Anti-IgE Asthma Therapies ruhMAb E-25*NS*Milgrom H.N Engl J Med.19
32、99 23;341(26):1966-73.Sx.ASTHMA: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.AST
33、HMA:a case in pointHer dyspnea 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“health
34、y diet and takes lots of vitamins”.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 i
35、nhaler,because they dont work and shes fearful of their adverse effects.COPD: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:.Consi
36、derations in Asthma Therapy Efficacy Convenience Control Adverse effects.Adverse effects of Asthma Therapy Beta agonists:tremor,tachycardia Inhaled steroids:Voice,Bones,?Metabolic LKRAs:Headache Prednisone:Cushings syndrome.012340130135140145140145150012346.56.05.55.04.50.0Time(yrs)Time(yrs)Standing
37、 Height(cm)Standing-height Velocity(cm/yr)N Engl J Med 2000;343:1054-63.BudesonideNedocromilPlaceboBudesonideNedocromilPlaceboLong-Term Effects of Budesonide or Nedocromil in Children with Asthma.The Rule of Twos(Who Needs Controller Therapy)Two beta-agonist canisters/yearTwo doses of beta-agonist/w
38、eekTwo nocturnal awakenings/monthTwo unscheduled visits/yearTwo prednisone bursts/year.2002 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
39、-30%Daily low-dose inhaled corticosteroidsOR Leukotriene modifier,theophylline.2002 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 l
40、ong-acting Beta agonist OR Leukotriene modifier,theophylline.2002 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).
