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Chronic Obstructive Pulmonary Disease (COPD) 10.22.09 Jaime Palomino, MD Pulmonary/CCM Tulane University INTRODUCTION COPD is the most important lung disease in U.S. 25% of ED visits for Dyspnea 4th cause of death Definition Disease state characterized by airflow obstruction that is no longer fully reversible and is usually progressive Accelerated declined in FEV1 from 30ml/year after 30y to 60ml “Preventable and treatable” Age-Related Decline in FEV1 Is Accelerated in Smokers FEV1 (% of value at age 25 y) Never smoked or not susceptible to smoke Stopped at 45 y Stopped at 65 y Smoked regularly and susceptible to its effects 100 75 50 Disability 25 Death 0 25 50 Age (y) FEV1, forced expiratory volume in 1 second. Adapted with permission from Fletcher C, Peto R. BMJ. 1977;1:1645-1648. 75 Epidemiology COPD is the fourth leading cause of death in the US.1 >25 million people in US have impaired lung fxn Annual cost of COPD in the US ~ $30.4 billion (ALA) office visits, diagnostic procedures, medications, and emergency and hospital services 1.Centers for Disease Control and Prevention. Mortality patterns—US, 1997. MMWR. 1999;48:664-678. Proportion of 1966 mortality rate Mortality of COPD Is Increasing 2.0 CHD Stroke COPD All Other Causes - 45% - 58% + 71% - 15% 1.5 1.0 0.5 0 1966-1986 COPD is the only leading cause of death that is increasing. Adapted with permission from Higgins MW, Thom T. In: Clinical Epidemiology of COPD. 1990:23-43. COPD – Pathogenesis Cosio et al. NEJM 2009;360:2445-54 Cosio et al. NEJM 2009;360:2445-54 COPD – Immunology Cosio et al. NEJM 2009;360:2445-54 Cosio et al. NEJM 2009;360:2445-54 Cosio et al. NEJM 2009;360:2445-54 COPD – Pathogenesis Sethi et al. NEJM 2008;359:2355-65 COPD – Risk Factors ACCP Pulmonary Board Review. 2007 Diagnosis of COPD History Smoking, occupational history Spirometry: FEV1, FEV1/FVC 6 minute walk to monitor fxnl status distance a patient can walk on a flat path in 6 minutes practical and reliable way to measure level of everyday impairment and exercise tolerance Differential Diagnosis: Asthma Versus COPD1-3 COPD Asthma Age of onset Usually > 35-40 years Any age (usually 40 years) Smoking history Usually 20 pack-years Minimal Positive family history Uncommon* Usually History of atopy Unimportant Often positive Pattern of symptom occurrence Nonspecific Nocturnal awakenings; early-morning symptoms Reversibility of airway obstruction Only partially reversible with smoking cessation and bronchodilator use Usually near-normal pulmonary function with appropriate therapy Triggers of exacerbations Infections, inhalant exposure Specific identifiable triggers *Except for 1-antitrypsin deficiency 1. NCAP. J Respir Dis. 2000;21(suppl):S5-S21. 2. American Thoracic Society. Am J Respir Crit Care Med. 1995;152:S77-S121. 3. Kuritzky L. Primary Care (Special Edition). 1999;3. A Comparison of Four Sets of Staging Criteria for COPD Sutherland, E. R. et al. N Engl J Med 2004;350:2689-2697 COPD Severity (GOLD Guidelines) ACCP Pulmonary Board Review. 2007 Deterioration in Lung Function in Patients with COPD Sutherland, E. R. et al. N Engl J Med 2004;350:2689-2697 ACCP Pulmonary Board Review. 2007 Pulmonary Hyperinflation in Patients with COPD Sutherland, E. R. et al. N Engl J Med 2004;350:2689-2697 Variables and Point Values Used for the Computation of the Body-Mass Index, Degree of Airflow Obstruction and Dyspnea, and Exercise Capacity (BODE) Index Celli, B. R. et al. N Engl J Med 2004;350:1005-1012 Celli et al. CHEST 2008;133:1451-1462 Medications – Anticholinergics Short-Acting: Ipratropium: Inhaled, nebs, (AtroventHFA®) Long-Acting: Tiotropium (Spiriva®) Medications – Beta Agonists Short-Acting: Albuterol (ProAir-HFA®, Proventil-HFA®, Ventolin-HFA®) Pirbuterol (Maxair®) Metaproterenol (nebs) Levalbuterol (Xopenex® nebs, Xopenex-HFA®) Long-Acting: Arformoterol (Brovana® nebs) Formoterol (Foradil®, Perforomist® nebs) Salmeterol (Serevent Diskus®) Medications – ICS Flunisolide (Aerobid®) Ciclesonide (Alvesco®) Mometasone (Asmanex Twisthaler®) Triamcinolone (Azmacort®) Fluticasone (Flovent Diskus®, Flovent HFA®) Budesonide (Pulmicort Flexhaler®, Pulmicort Respules® nebs) Beclomethasone (QVAR®) Medications – Combinations SABA + SAMA: Albuterol/Ipratropium (Combivent®, Duoneb®) LABA + ICS: Fluticasone/Salmeterol (Advair Diskus®, Advair HFA®) Budesonide/Formoterol (Symbicort®) Medications – Others Theophylline (Theo-24®, Uniphyl®) Calverley et al. NEJM 2007;356:775-89 Calverley et al. NEJM 2007;356:775-89 Calverley et al. NEJM 2007;356:775-89 Celli et al. AJRCCM 2008;178:332-338 Calverley et al. NEJM 2007;356:775-89 Drummond et al. JAMA 2008;300:2407-2416 Sin et al. Lancet 2009;374:712-19 Tashkin et al. NEJM 2008;359:1543-54 Tashkin et al. NEJM 2008;359:1543-54 Tashkin et al. NEJM 2008;359:1543-54 Tashkin et al. NEJM 2008;359:1543-54 Lee et al. Arch Intern Med. 2009;169:1403-1410 Welte et al. AJRCCM.2009;180:741-750 Changes in Lung Function Number of Severe Exacerbations Welte et al. AJRCCM.2009;180:741-750 Lee et al. Ann Intern Med 2008;149:380-390 Singh et al. JAMA 2008;300:1439-1450 Tashkin et al. NEJM 2008;359:1543-54 Medications Theophylline or PDE Inhibitors May have a “come-back” Lower levels (8-13 mg/dL) Improvement in corticosteroid resistance (HDAC2) Phosphodiesterase E4 inhibitors Calverley et al. Lancet 2009;374:685-694 Smoking cessation Smoking cessation: single most effective way to improve clinical outcomes in patients at all stages of COPD (asxsevere).1-4 After cessation, FEV1 rate of decline may decrease to the rate found in healthy nonsmokers.5,6 35% abstinent at 1 year, 22% at 5 years 1. The National COPD Awareness Panel (NCAP). Guidelines for early detection and management of COPD. J Resp Dis. 2000;21(suppl):S5S21. 2. Centers for Disease Control and Prevention. The Surgeon General’s 1990 report on the health benefits of smoking cessation: executive summary – introduction, overview, conclusions. MMWR. 1990;39(RR-12):2-10. 3. Anthonisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled bronchodilator on the rate of decline in FEV1: the Lung Health Study. JAMA. 1994;272:1497-1505. 4. Kanner RE. Early intervention in chronic obstructive pulmonary disease: a review of the Lung Health Study results. Med Clin North Am. 1996;80:523-547. 5. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1:1645-1648. 6. Higgins MW, Enright PL, Kronmal RA, et al. Smoking and lung function in elderly men and women. JAMA. 1993;269:2741-2748. Smoking cessation Ask: every patient, during each clinic visit Advise: urge to quit Assess: willingness to quit Assist: quit plan, counseling, social support, pharmacotherapy Arrange: follow-up contract Vaccination Pneumococcal vaccination Annual influenza vaccination Long-Term Oxygen Therapy Indicated for PaO2 <55 mm Hg or SaO2 <88%1 Improves1-4: – – – – – Survival in hypoxemic patients Cognitive function, affect Exercise performance Sleep quality Activities of daily living 1. NCAP. J Respir Dis. 2000;21(suppl):S5-S21. 2. Report of the Medical Research Council Working Party. Lancet. 1981;681-686. 3. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93:391-398. 4. Bye et al. Am Rev Respir Dis. 1985;132:236-240. Pulmonary Rehabilitation Casaburi et al. NEJM 2009;360:1329-35 Pulmonary Rehabilitation Improves (better than other COPD therapies): Exercise capacity Severity of dyspnea Health-related quality of life Reductions in hospitalization Improvements in cost-effectiveness Reduction in depression and anxiety Improves cognitive function and self-efficacy Survival benefit has not been demonstrated Reimbursement varies Casaburi et al. NEJM 2009;360:1329-35 Pulmonary Rehabilitation Indications: 3 times/week. 3-4 hrs/session. 6 – 12 weeks Endurance exercise leg muscles GOLD Stage 3 or 4 Walking, stationary cycling, treadmill Resistance-exercise component Upper extremities exercise Bronchodilators, oxygen, NIPPV, heliox, anabolic steroids Education, smoking cessation, nutrition Casaburi et al. NEJM 2009;360:1329-35 Treatment - COPD Lung Transplant < 65 y/o High BODE index Effects on survival remains controversial LVRS (pneumoplasty) Upper lobe disease Limited exercise performance after pulmonary rehabilitation FEV1 : 20 -35 % predicted Bronchoscopic placement of one-way valves or biological substances Tillie-Leblond et al. Ann Intern Med. 2006;144:390-396 Rizkallah et al. CHEST 2009;135:786-793 Zvezdin et al. CHEST 2009;136:376-380 Treatment - NPPV NPPV fewer intubations, decreased mortality, and shortened MICU admissions Indications for NPPV pH < 7.20 RR > 25 MS change worsening hypercapnia