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Chronic Obstructive Pulmonary Disease and Asthma Update

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 .

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Chronic Obstructive Pulmonary Disease and Asthma Update

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  1. Chronic Obstructive Pulmonary Diseaseand Asthma Update John L. Faul, MD FCCP Assistant Professor, Division of Pulmonary/Critical Care Medicine Stanford University

  2. COPD: Outline • Epidemiology • Definitions • Medical management • Hypoxia • Infections • Vaccination

  3. Universal Problem

  4. COPD: epidemiology 14 million in the US with COPD 12.5 million with chronic bronchitis 1.65 million with emphysema 4th leading cause of death in US 3rd most frequent diagnosis of patients receiving home care

  5. Prevalence of COPD in the US 90 † † † † 80 † • Since 1987, the prevalence of COPD among women has been significantly higher than that among men † † † † † † † † 70 † † 60 50 Rate/1,000 Population* 40 Male Female Total 30 20 10 0 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 Year *Age-adjusted to 2000 US population. †Represents a statistically significant difference from rate among males. Mannino et al. MMWR. 2002;51(SS-6):1-16.

  6. COPD:The Usual Suspects

  7. 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 all COPD cases) occupational exposures to dusts and fumes

  8. Lung function declines with age

  9. Elastic tissue is lost in emphysema

  10. 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 causes 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”

  11. Pink puffers &Blue bloaters

  12. COPD: Hyperinflation Increased AP diameter Increased retrosternal airspace Flat diaphragms

  13. COPD

  14. 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 be done Home O2 costs in the US/yr: $ 2,400,000,000

  15. Oxygen Dissociation Curve __ 100 At 80mmHg, 95% sat __ At 60mmHg, 90% sat 80 At 40mmHg, 70% sat __ Hemoglobin Saturation % 60 __ 40 __ 20 __ i i i 0 40 60 80 PaO2 (mmHg) Below PaO2 = 60mmHg, Hemoglobin rapidly loses oxygen carrying capacity (West: Textbook of Physiology)

  16. Hypoxic Pulmonary Vasoconstriction • The lung regulates blood flow according to its oxygen content • A 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-sensitive chemoreceptors located in the pulmonary arteriole are the dominant controllers of pulmonary vascular tone Fishman AP: Hypoxia on the pulmonary circulation. How and where it acts. Circ Res 1976; 38:221–231

  17. COPD: a case in point CC: 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 included asthma, bronchitis, and emphysema she wants to know exactly what she has...

  18. COPD: a case in point Her 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...

  19. 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 she’s not sure this one helps, but maybe theophylline 200 mg BID some doctor gave her this “years ago” prednisone 10 mg QD continuously for 3 years with occasional increases she’s never taken any estrogen replacement

  20. COPD: a case in point HPI: She’s takes antibiotics 6-7 times/year when her breathing “gets really bad” She’s been onoxygenbut doesn’t like it She’s 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

  21. Exacerbation of COPD Anthonisen et al,Ann Int Med 1987;106: 196 Saint et al, JAMA 1995;273(12):957

  22. Exacerbation of COPD Non infectious and infectious Infections include viral Controversial if all sputum cultures are causative For patients with 2 or especially 3 cardinal features, antibiotics are useful Short courses of antibiotics are useful Amsden GW et al., Chest 2003: 123:772-777

  23. Antimicrobial Therapy Oral agents used earlier in therapy Monotherapy used whenever possible Patient compliance (once-daily dosing) Comprehensive disease management

  24. Vaccinations and COPD Annual 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 years No 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.

  25. COPD: oral steroids for ER discharges * * * % relapse free Day n = 147, Pred 40/day for 10 days Aaron SD. N Engl J Med. 2003;348 (26):2618-25.

  26. Vlad the Inhaler

  27. COPD: inhaled steroids and LABA ** ** Calverley P. Lancet. 2003 Feb 8;361(9356):449-56 * Change In FEV1 (ml) * n = 1465

  28. Peak Flow RatesTiotropium versus Salmeterol Donohue JF Chest 2002.122:47-55.

  29. 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.

  30. COPD: smoking cessation % abstinence * * Tonstad S. Eur Heart J. 2003 May;24(10):946-55.

  31. COPD: advanced therapies Surgery for emphysema: Bullectomy Lung volume reduction surgery (LVRS) Transplantation

  32. GOLD ’03 Classification of COPD * respiratory failure: PaO2 < 60 mm Hg with or w/o PaCO2 > 50 mm Hg

  33. Therapy at Each Stage of COPD * FEV1/FVC < 70% Gold Update 2003

  34. COPD: management Stop smoking Long-term oxygen Inhaled steroids and long-acting beta agonists Diet and exercise Treat acute exacerbations Monitor lung function Vaccinate

  35. 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 million • Estimated direct and indirect medical costs: $16 billion (needs validation) Morb Mortal Wkly Rep. 2002 March 29; 51:1-13.

  36. Asthma Pathophysiology Smooth Muscle Dysfunction AirwayInflammation • Bronchoconstriction • Bronchial Hyperreactivity • Hypertrophy • Hyperplasia • Inflammatory Cell Activation • Mucosal Edema • Proliferation • Epithelial Damage • B. Membrane Thickening Symptoms/Exacerbations

  37. Spirometry 5 Pre-albuterol 4 Post-albuterol 3 Predicted 2 Flow 1 (l/s) 0 1 2 3 4 5 -2 -4 -6 Vol (l)

  38. Eosinophils in Human Bronchi

  39. Changes in EG2 during FP therapy Faul JL, Thorax 1998. 53, 753-61

  40. Change in Mean Peak Flow with therapy Haahtela T. N Engl J Med 1994, 331: 700

  41. Change in Mean Peak Flow with therapy Greening AP. Lancet 1994, 344: 219-24

  42. Comparison of Asthma Therapies 1.0 0.8 0.6 0.4 0.2 * 3% 11% 35% Probability of Remaining in the Study 49% Sal/FP 100/50FP 100Salmeterol 50Placebo 0 7 14 21 28 35 42 49 56 63 70 77 Study Day Kavuru M et al. J Allergy Clin Immunol. 2000;105:1108-1116.

  43. Time to First Exacerbation 100 95 90 85 80 75 FP 88 mcg b.i.d. + Salmeterol FP 220 mcg b.i.d. * Exacerbation-FreePatients (%) 0 2 4 6 8 10 12 14 16 18 20 22 24 Time to First Exacerbation (weeks) Matz J et al. J Allergy Clin Immunol. 2000;105:162S.

  44. Patients Treated With ADVAIR™ Diskus® 100/50 had a Significantly Greater Improvement in FEV1 Sal/FP 100/50 FP 100 Salmeterol 50 Placebo 25%[0.51L] * 30 25 20 15 10 5 0 Mean Change from Baselinein FEV1 (%) 15%[0.28L] 5%[0.11L] 2%[0.01L] 0 2 4 6 8 10 12 Endpoint Week *P0.008 vs FP 100, salmeterol 50, and placebo at endpoint. Doses in mcg b.i.d. Kavuru et al. J Allergy Clin Immunol. 2000;105:1108-1116.Data on file, Glaxo Wellcome Inc.

  45. Patients (15 Years) Not Controlled on PRN Beta-AgonistsImproved FEV1 (Study 1 and Extension) 30 25 20 15 10 5 0 -5 Placebo Montelukast Beclomethasone Primary Study Cumulative Extension FEV1 (% Change from Baseline; Mean± SE) 0 3 6 9 12 15 19 23 31 39 47 52 60 68 76 84 92 100 108 116 124 132 140 Study Weeks (Postrandomization) Noonan et al. Am J Respir Crit Care Med. 1999;159(3):640. Reiss et al. Arch Intern Med. 1998;158:1213-1220.

  46. Patients (15 Years) Not Controlled on PRN Beta-Agonists 1 0.95 0.90 0.85 0.80 0.75 0.70 Beclomethasone (n=248) Proportionof PatientsWithout Asthma Attack Montelukast (n=379) Placebo (n=253) 0 10 20 30 40 50 60 70 80 90 Days Since Randomization P=0.006 Montelukast vs placebo P=0.001 Beclomethasone vs placebo P=0.129 Montelukast vs beclomethasone • In this study, all patients benefited from • mandatory use of spacers, • enforced compliance, and • rigorous monitoring of patients Malmstrom et al. Ann Intern Med. 1999;130:487-495.

  47. Anti-IgE Asthma Therapies ruhMAb E-25 ** ** * NS Sx Milgrom H. N Engl J Med. 1999 23;341(26):1966-73.

  48. ASTHMA: a case in point CC: Ms. B. is a 22y.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 exactly what she has...

  49. 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 ... She’s a Stanford student who eats a “healthy diet and takes lots of vitamins”

  50. A case in point She takes the following medications: albuterol MDI 2-4 puffs QID and prn this is her “favorite” medicine prednisone 10 mg QD she is just finishing a steroid taper that was prescribed after her most recent Emergency Room visit she’s never taken any steroid inhaler, because they don’t work and she’s fearful of their adverse effects

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