1、Chronic Obstructive Pulmonary Disease and Asthma Update,John L. Faul, MD FCCP Assistant Professor, Division of Pulmonary/Critical Care Medicine Stanford University,COPD: Outline,Epidemiology Definitions Medical management Hypoxia Infections Vaccination,Universal Problem,COPD: epidemiology,14 million
2、 in the US with COPD 12.5 million with chronic bronchitis 1.65 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 ra
3、te among males.Mannino et al. MMWR. 2002;51(SS-6):1-16.,Rate/1,000 Population*,0,20,30,40,50,60,70,80,90,1980,1982,1984,1986,Year,Male Female Total,10,1988,1990,1992,1994,1996,1998,2000,Since 1987, the prevalence of COPD among women has been significantly higher than that among men,COPD: The Usual S
4、uspects,COPD: risk factors,tobacco smoking accounts for 80-90% of the risk of developing COPD age of starting, total pack-years and current smoking status are predictive of mortality only 15% of smokers develop clinically significant COPD alpha1-antitrypsin deficiency (accounts for less than 1% of a
5、ll COPD cases) occupational exposures to dusts and fumes,Lung function declines with age,Elastic tissue is lost in emphysema,COPD: definitions,Chronic 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 cau
6、ses of chronic cough have been excluded” Emphysema-a pathologic definition: “abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls”,Pink puffers & Blue bloaters,COPD: Hyperinflation,Increased retrosternal airspace,Flat diaphragms
7、,Increased AP diameter,COPD,COPD: Oxygen therapy,Oxygen therapy in COPD:extends life in hypoxemic patients NOTT trial, Ann Int Med 1980;93: 391-398 MRC trial, Lancet 1981; 1: 681-685 strengthens cardiac function, improves exercise performance and ADLs when FEV1 1.0 L (or 50% predicted) an ABG should
8、 be done Home O2 costs in the US/yr: $ 2,400,000,000,Oxygen Dissociation Curve,100,80,60,Below PaO2 = 60mmHg, Hemoglobin rapidly loses oxygen carrying capacity (West: Textbook of Physiology),Hemoglobin Saturation %,40,60,80,_,_,_,_,_,40,_,20,0,i,i,i,At 80mmHg, 95% sat,At 60mmHg, 90% sat,At 40mmHg, 7
9、0% sat,PaO2 (mmHg),Hypoxic Pulmonary Vasoconstriction,The lung regulates blood flow according to its oxygen contentA low venous oxygen content (low oxygen content in the pulmonary artery) prevents blood flow to the lung,Blood Flow %,Air sack (Alveolar) Oxygen,West: Textbook of Physiology,Oxygen-sens
10、itive chemoreceptors located in the pulmonary arteriole are the dominant controllers of pulmonary vascular toneFishman AP: Hypoxia on the pulmonary circulation. How and where it acts. Circ Res 1976; 38:221231,COPD: a case in point,CC: Mrs. H. is a 67 y.o female with worsening dyspnea x several years
11、 who presents for 2nd opinion regarding diagnoses, and management, of her “breathing problem” her past diagnoses have included asthma, bronchitis, and emphysema she wants to know exactly what she has.,COPD: a case in point,Her dyspnea is much worse in the last year, to the point that she can no long
12、er 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,She takes the following medications: albuterol MDI 2-4 puffs QID and prn this is her “favorite” medicine atrovent MDI 2 puffs QID shes not s
13、ure this one helps, but maybe theophylline 200 mg BID some doctor gave her this “years ago” prednisone 10 mg QDcontinuously for 3 years with occasional increases shes never taken any estrogen replacement,COPD: a case in point,Shes takes antibiotics 6-7 times/year when her breathing “gets really bad”
14、 Shes been on oxygen but doesnt like it Shes too short of breath to do any exercise She has been in the hospital 4 times in the last year and was intubated once, 6 months ago,HPI:,Exacerbation of COPD,Anthonisen et al,Ann Int Med 1987;106: 196 Saint et al, JAMA 1995;273(12):957,Exacerbation of COPD,
15、Non infectious and infectiousInfections include viralControversial if all sputum 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 Therapy,Oral agents used
16、earlier in therapy Monotherapy used whenever possible Patient compliance (once-daily dosing) Comprehensive disease management,Vaccinations and COPD,Annual influenza vaccine: Reductions in exacerbation rates particularly within 3 weeks. No evidence of an effect of intranasal live attenuated virus whe
17、n this was added to inactivated intramuscular vaccination. Pneumococcal vaccine every 5 yearsNo evidence that pneumococcal vaccine reduces the severity of COPD,Poole PJ. Cochrane Database Syst Rev. 2000;(4):CD002733. Leech JA. CMAJ. 1987: 136(4):361-5.,COPD: oral steroids for ER discharges,Aaron SD.
18、 N Engl J Med. 2003;348 (26):2618-25.,% relapse free,Day,n = 147, Pred 40/day for 10 days,*,*,*,Vlad the Inhaler,COPD: inhaled steroids and LABA,Calverley P. Lancet. 2003 Feb 8;361(9356):449-56,Change In FEV1 (ml),n = 1465,*,*,*,*,Peak Flow Rates Tiotropium versus Salmeterol,Donohue JF Chest 2002.12
19、2:47-55.,COPD: smoking cessation,Tobacco smoking is the most important factor in COPD, and stopping smoking is the only intervention known 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 the
20、rapies,Bullectomy Lung volume reduction surgery (LVRS) Transplantation,Surgery for emphysema:,GOLD 03 Classification of COPD,* respiratory failure: PaO2 50 mm Hg,Therapy at Each Stage of COPD,Gold Update 2003,* FEV1/FVC 70%,COPD: management,Stop smoking Long-term oxygen Inhaled steroids and long-act
21、ing beta agonistsDiet and exercise Treat acute exacerbations Monitor lung function Vaccinate,Asthma Facts in the United States,Annual number of hospitalizations: 478,000 Annual number of deaths from asthma: 4,657 Annual number of work days lost: 14.5 million Annual number of school days lost: 14 mil
22、lion Estimated direct and indirect medical costs: $16 billion (needs validation),Morb Mortal Wkly Rep. 2002 March 29; 51:1-13.,Smooth Muscle Dysfunction,Airway Inflammation,Inflammatory Cell Activation Mucosal Edema Proliferation Epithelial Damage B. Membrane Thickening,Bronchoconstriction Bronchial
23、 Hyperreactivity Hypertrophy Hyperplasia,Symptoms/Exacerbations,Asthma Pathophysiology,Flow,(l/s),Vol (l),-2,0,-4,1,3,2,4,5,2,1,3,4,5,-6,Pre-albuterol,Post-albuterol,Predicted,Spirometry,Eosinophils in Human Bronchi,Changes in EG2 during FP therapy,Faul JL, Thorax 1998. 53, 753-61,Change in Mean Pea
24、k Flow with therapy,Haahtela T. N Engl J Med 1994, 331: 700,Change in Mean Peak Flow with therapy,Greening AP. Lancet 1994, 344: 219-24,Study Day,Probability of Remaining in the Study,1.0 0.8 0.6 0.4 0.2,Sal/FP 100/50 FP 100 Salmeterol 50 Placebo,* 3%,0 7 14 21 28 35 42 49 56 63 70 77,11%,35%,49%,Co
25、mparison of Asthma Therapies,Kavuru M et al. J Allergy Clin Immunol. 2000;105:1108-1116.,Time to First Exacerbation,*,100 95 90 85 80 75,0 2 4 6 8 10 12 14 16 18 20 22 24,Time to First Exacerbation (weeks),Exacerbation-Free Patients (%),FP 88 mcg b.i.d. + Salmeterol FP 220 mcg b.i.d.,Matz J et al. J
26、 Allergy Clin Immunol. 2000;105:162S.,Kavuru et al. J Allergy Clin Immunol. 2000;105:1108-1116. Data on file, Glaxo Wellcome Inc.,Week,Mean Change from Baseline in FEV1 (%),30 25 20 15 10 5 0,0 2 4 6 8 10 12 Endpoint,15% 0.28L,5% 0.11L,2% 0.01L,Sal/FP 100/50 FP 100 Salmeterol 50 Placebo,25% 0.51L *,
27、*P0.008 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;159(3):640. Reiss et al. Arch Intern Med. 1998;158:1213-1220.,FEV1 (% Change from Ba
28、seline; Mean SE),Study Weeks (Postrandomization),30 25 20 15 10 5 0 -5,0,3,6,9,12,15,19,23,31,39,47,52,60,68,76,84,92,100,108,116,124,132,140,Cumulative Extension,Placebo Montelukast Beclomethasone,Primary Study,Patients (15 Years) Not Controlled on PRN Beta-Agonists Improved FEV1 (Study 1 and Exten
29、sion),Proportion of Patients Without Asthma Attack,Days Since Randomization,Beclomethasone (n=248),Montelukast (n=379),Placebo (n=253),P=0.006 Montelukast vs placebo P=0.001 Beclomethasone vs placebo P=0.129 Montelukast vs beclomethasone,1 0.95 0.90 0.85 0.80 0.75 0.70,0,10,20,30,40,50,60,70,80,90,P
30、atients (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 M
31、ed. 1999 23;341(26):1966-73.,Sx,ASTHMA: a case in point,CC: 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 included asthma, bronchitis, and allergies she wants to know exac
32、tly what she has.,ASTHMA: a case in point,Her 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 Stanf
33、ord student who eats a “healthy diet and takes lots of vitamins”,A case in point,She takes the following medications: albuterol MDI 2-4 puffs QID and prn this is her “favorite” medicineprednisone 10 mg QDshe is just finishing a steroid taper that was prescribed after her most recent Emergency Room v
34、isit shes never taken any steroid inhaler, because they dont work and shes fearful of their adverse effects,COPD: a case in point,Shes 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 o
35、nce, but has not been intubated,HPI:,Considerations 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,0,1,2,3,4,0,130,135,140,145
36、,140,145,150,0,1,2,3,4,6.5,6.0,5.5,5.0,4.5,0.0,Time (yrs),Time (yrs),Standing Height (cm),Standing-height Velocity (cm/yr),N Engl J Med 2000;343:1054-63.,Budesonide,Nedocromil,Placebo,Budesonide,Nedocromil,Placebo,Long-Term Effects of Budesonide or Nedocromil in Children with Asthma,The Rule of Twos
37、 (Who Needs Controller Therapy),Two beta-agonist canisters/year Two doses of beta-agonist/week Two nocturnal awakenings/month Two unscheduled visits/year Two prednisone bursts/year,2002 NAEPP GUIDLINES,STEP 1: Mild Intermittent AsthmaSymptoms Present 80% predictedPEF variability 20%No daily medicati
38、on Severe exacerbations may occur a course of oral corticosteroids,2002 NAEPP GUIDELINES,Step 2: Mild Persistent AsthmaSymptoms present 2x/weekbut 2x/monthFEV1 and PEF 80% predictedPEF variability 20-30% Daily low-dose inhaled corticosteroids OR Leukotriene modifier, theophylline,2002 NAEPP GUIDELIN
39、ES,Step 3: Moderate Persistent AsthmaSymptoms dailyExacerbations affect activityNighttime symptoms 1x/weekFEV1 and PEF 60-80% predictedPEF variability 30% Low-medium dose inhaled corticosteroids with long-acting Beta agonist OR Leukotriene modifier, theophylline,2002 NAEPP GUIDELINES,Step 4: Severe Persistent AsthmaContinual Symptoms Exacerbations affect activityNighttime symptoms frequentFEV1 and PEF 30% High-dose inhaled corticosteroids And Long-acting beta agonist AND oral corticosteroids (2mg/kg/day),
