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COPD M3 lecture Tammy Wichman MD Assistant Professor of Medicine Pulmonary-Critical Care • A 55 year old male presents to the office with worsening shortness of breath over the past 6 months. He has a morning cough productive of thick white sputum. He denies any chest pain. His weight has been stable. He has a 45 pack year smoking history and continues to smoke ½ pack per day. He drinks several beers on the weekends. He is divorced and works as an engineer. What of the following tests should you order to work up his dyspnea? • Pulmonary Function Tests including DLCO • Chest x-ray • Spiral CT to rule out chronic thromboembolic disease • High-resolution CT to evaluate for interstitial fibrosis • Methacholine challenge • Allergy Skin Testing • Pre- and Post-Bronchodilator spirometry • Arterial blood gas • 6 minute walk Diagnosis of COPD SYMPTOMS EXPOSURE TO RISK FACTORS cough sputum dyspnea tobacco occupation indoor/outdoor pollution SPIROMETRY Spirometry • The severity of disease in COPD is assessed by _________. The classification system is called ________. • Disease severity ________ (is or is NOT) associated with mortality. Deterioration in Lung Function 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 Kaplan-Meier Survival Curves for the Four Quartiles of the Body-Mass Index, Degree of Airflow Obstruction and Dyspnea, and Exercise Capacity Index (Panel A) and the Three Stages of Severity of Chronic Obstructive Pulmonary Disease as Defined by the American Thoracic Society (Panel B) Celli, B. R. et al. N Engl J Med 2004;350:1005-1012 Other tests • Bronchodilator reversibility – Helpful to rule out a diagnosis of asthma, to establish a patient’s best attainable lung function, to gauge a patient’s prognosis, and to guide treatment decisions – Even patients who do not show a significant FEV1 response to a shortacting bronchodilator test may benefit symptomatically • CXR-seldom diagnostic unless obvious bullous disease is present but it is valuable in excluding alternative diagnosis • ABG-should be measured in patients with FEV1<40% predicted or with cor pulmonale • Alpha-1 antitrypsin deficiency: in patients who develop COPD at a young age or who have a family history COPD Definition Fill in the blanks • Disease state characterized by ____________ that is not fully __________. The _______________ is usually both progressive and associated with an abnormal inflammatory response of the lungs to _______________. COPD Definition • Disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. • Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease www.goldcopd.com Lancet 2003;362:1053-61 Pathology of COPD Fill in the boxes SMOKING Pathology Physiologic Consequence Large airways 1. 2. 1. Small airways 1. 2. 3. 1. 1. Alveoli 1. Pathology • What is the single most effective intervention to stop the progression of COPD in this patient? • How would you do this? Be specific. Smoking Cessation • Single most effective (and cost effective) intervention to reduce the risk of developing COPD and stop its progression • Brief tobacco dependence treatment is effective and every tobacco user should be offered at least this treatment at every visit to the health care provider Strategies to Help the Patient Willing to Quit Smoking • 1. ASK: Systematically identify all tobacco users at every visit. • 2. ADVISE: Strongly urge all tobacco users to quit. • 3. ASSESS: Determine willingness to make a quit attempt. • 4. ASSIST: Aid the patient in quitting • 5. ARRANGE: Schedule follow-up contact Pharmacotherapy • Nicotine replacement reliably increases longterm smoking abstinence rates • Bupropion and Nortriptyline have been shown to increase long-term quit rates Effects of Smoking Cessation on Natural History of FEV1 FEV1 (Percentage of Value at Age 25 Years) 100 75 50 Disability 25 Death † † 0 25 50 75 Age (Years) Smoked Regularly and Susceptible to Its Effects Stopped at Age 45 Years Stopped at Age 65 Years Never Smoked or not Susceptible to Smoke Fletcher C, Peto R. Br Med J. 1977;1:1645-1648. Anthonisen et al. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med 2002;166(5)675-9. Anthonisen et al. Lung Health Study Research Group. Ann Intern Med 2005;142:233-9 Mortality benefit despite the fact that only 21.7% of smoking intervention group quit vs 5.4% of usual care group • A 61 year old female presents to the office with worsening shortness of breath. Symptoms have been gradually worsening over the past several years. She has a chronic cough productive of white sputum. Patient was started on oxygen by her primary care physician last month and was referred to you for further evaluation. Her past medical history is significant for hypertension. She quit smoking several years ago. She drinks one glass of wine a day. She recently quit her job as a day care provider. She denies any fever or chills. Her current medications are: • VoSpire (Albuterol) ER 8 mg po Q 12 hours • Atrovent nebulizers Q 6 hours • Prednisone 10mg po Q day • Theophylline 200mg po BID • Inderal (Propranolol) 80 mg po BID • On exam, T 37.5 HR 82 R 16 BP 135/65 Sats 95% on 2L O2 by nasal cannula. She has a mildly increased P2 on cardiac exam. She has a prolonged expiratory phase on lung exam with scattered end-expiratory wheezes. The rest of her exam is normal. Her CXR is available for review. Her pulmonary function tests are: FVC 1.56 L 59% predicted improving to 1.9 L 72% predicted, a 22% improvement. FEV1 0.67 36% predicted improving to 0.92 L a 37% improvement. TLC 120% predicted. RV 191% predicted and DLCO 38% predicted. • How would you rate the severity of her disease? • What adjustments should be made to her medical regimen? • Can anything be done to prolong her life? • Are there any non-medical options available to improve her condition? Which of the following are objectives of COPD management? • • • • • • • • • • Prevent disease progression Improve pulmonary function tests Relieve symptoms Repair emphysematous lungs Improve exercise tolerance Improve health status Decrease oxygen requirements Prevent and treat exacerbations Reduce mortality Minimize side effects from treatment Objectives of COPD Management • • • • • • • • Prevent disease progression Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Prevent and treat complications Reduce mortality Minimize side effects from treatment Monitor Disease Progression • COPD is a progressive disease, and a patient’s lung function can be expected to worsen over time, even with the best available care Manage Stable COPD • Stepwise increase in treatment, depending on the severity of the disease. • Patient education improves skills, ability to cope with illness and health status. • None of the existing medications for COPD has been shown to modify the long-term decline in lung function. So pharmacotherapy is used to decrease symptoms, reduce the frequency and severity of exacerbations, improve health status, and improve exercise tolerance Manage Stable COPD: Bronchodilators • Bronchodilator medications are central to the symptomatic management of COPD. They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms. – – – – – Alleviate symptoms Improve exercise tolerance Improve quality of life Decrease the incidence of exacerbations Decrease hyperinflation • Inhaled therapy is preferred Manage Stable COPD: Bronchodilators • Beta2-agonists: increase cyclic adenosine monophosphate levels and promote airway smoothmuscle relaxation – Short acting: Albuterol (Proventil) – Long acting: Salmeterol (Serevent) and Formoterol fumarate (Foradil) • Anticholinergics: block muscarinic receptors – Short acting: Ipratropium bromide (Atrovent) – Long acting: Tiotropium bromide (Spiriva) • Combination: (Combivent, DuoNeb) Manage Stable COPD: Bronchodilators • Phosphodiesterase Inhibitors: increase intracellular cyclic adenosine monophosphate levels within airway smooth muscle – 3rd line agent – Improves respiratory muscle function, stimulates the respiratory center, decreases dyspnea, and enhances activities of daily living – Toxic side effects: tachyarrhythmias, nausea, vomiting, seizures – Monitoring should include intermittent serum level measurements: target range 8-12mcg/mL Inhaled Steroids (ICS) in Stable COPD • Glucocorticoids act at multiple points within the inflammatory cascade. • Regular treatment with ICS does not modify the long-term decline in FEV1. • Appropriate for symptomatic COPD patients with an FEV1 < 50% and repeated exacerbations (Stage III and IV). • ICS reduce frequency of exacerbations and improve health status (Evidence A). • ICS combined with long-acting b2-agonist more effective than individual components. Steroids in Stable COPD • GOLD guidelines recommend a trial of 6 weeks to 3 months of ICS to identify subset of patients who may benefit. • Short course of oral steroids is a poor predictor of long-term response to ICS. • Long-term treatment with oral steroids is NOT recommended (Evidence A): – No evidence of long-term benefit – Major side effects: skin damage, cataracts, diabetes, osteoporosis, secondary infection, psychosis, fluid retention Other pharmacologic treatments • Vaccines: Influenza vaccine reduces serious illness and death in COPD patients by 50%. Pneumococcal vaccine is recommended every 5 years although data in COPD patients is lacking. • Other anti-inflammatory agents: Cromolyn, nedocromil, and leukotriene inhibitors have not been adequately tested in patients with COPD • Alpha-1 Antitrypsin Augmentation Therapy: young patients with severe deficiency and established emphysema • Antibiotics are not recommended other than in treating infectious exacerbations (Doxycycline, amoxicillin, macrolide, fluoroquinolones) • Mucolytic agents: not recommended • Antioxidants (N-acetylcysteine) may reduce the frequency of exacerbations • Antitussives: contraindicated in stable COPD because cough is protective • Comprehensive pulmonary rehabilitation programs have been shown to improve all of the following EXCEPT: • A. Measured FEV1 • B. Respiratory symptoms • C. 6-Minute walk test • D. Need for outpatient care and inpatient hospitalizations • E. Symptoms of anxiety, depression, and lack of wellbeing Pulmonary Rehabilitation in Stable COPD • All COPD-patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A). • The minimum length of an effective rehab program is 2 months; the longer the better (Evidence B). • Comprehensive pulmonary rehabilitation program includes exercise training, nutrition counseling, and education. Manage Stable COPD: Oxygen • The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure (Stage IV) has been shown to increase survival (Evidence A). • Oxygen administration reduces hematocrit, pulmonary artery pressures, dyspnea, and rapid eye movement related hypoxemia during sleep. • Tailor prescription to patient: source, method of delivery, duration of use, flow rate at rest, during exercise, and sleep Lancet 2003;362:1053-61 • A 59 year old male presents with worsening shortness of breath. He was diagnosed with COPD several years ago and was told to wear oxygen at home. However, he doesn’t feel like he needs it. He continues to exercise for several minutes a day on the treadmill and does pullups. In the office, his O2 sats are 83% on room air so he is admitted to the hospital. T 98.9 HR 103 R 24 BP 142/82 Sats 91% on 6 L oxymizer. His weight is 144 lbs at 68 inches. He has temporal wasting. He has supraclavicular fullness, jugular venous distension to the jaw, a prominent P2 on cardiac exam. He has poor air movement throughout both lung fields. • Pulmonary function tests: FEV1/FVC 28.6% FEV1 0.51 L 18% predicted; FVC 1.8L 52% predicted. With albuterol, his FVC increases to 2.07 L, a 14% improvement. His TLC is 151% predicted. His RV is 359% predicted. • • • • • • How would you rate his severity of disease? How should this patient be treated? What (if any) bronchodilators would you use? Is there any role for inhaled corticosteroids? What about systemic corticosteroids? Any other beneficial interventions? True or False • COPD is a disease process limited to the lungs. _______ • COPD is the only disease in which mortality rates have been rising over the past several decades. _________ COPD is a systemic disease • • • • Systemic inflammation Skeletal muscle dysfunction Nutritional problems High prevalence of depression and anxiety – PRIME-MD: 1334 VA patients with COPD: 80% screened positive for depression or anxiety – Nicotine helps mitigate these symptoms Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 3.0 2.5 2.5 Coronary Heart Disease Stroke Other CVD COPD All Other Causes –59% –64% –35% +163% –7% 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 Trends in Age-Standardized Death Rates for the 6 Leading Causes of Death in the United States, 1970-2002 Jemal, A. et al. JAMA 2005;294:1255-1259. Copyright restrictions may apply. • COPD is the ___ leading cause of death in the United States. • A. 2nd • B. 4th • C. 6th • D. 10th Epidemiology • 4th leading cause of death in the USA • In 2000, WHO estimates 2.74 million deaths worldwide from COPD – In 2000, more women than men died of COPD in U.S. (59,936 vs 59,118) • Age-adjusted death rates are rising • High burden of disease – – – – Approx. 16 million office visits (USA, 1995) 500,000 hospitalizations for COPD Medical expenditures ~ 15 billion dollars/yr; $32 billion in direct and indirect costs in 2002 Management Stage 0: At Risk for COPD Characteristics • Chronic symptoms - cough - sputum • No spirometric abnormalities Recommended Treatment Avoidance of risk factors: Smoking cessation Influenza vaccination Management Stage I: Mild COPD Characteristics • FEV1/FVC < 70 % • FEV1 > 80 % predicted • With or without symptoms Recommended Treatment • Add Short-acting bronchodilator as needed Management of Stage II: Moderate COPD Characteristics •FEV1/FVC < 70% •50% < FEV1< 80% predicted •With or without symptoms Recommended Treatment •Add regular tx with long-acting BD •Pulmonary rehab Management of Stage III: Severe COPD Characteristics •FEV1/FVC < 70% •30% < FEV1 < 50% predicted •With or without symptoms Recommended Treatment Add ICS if repeated exacerbations Management of Stage IV: Very Severe COPD Characteristics •FEV1/FVC < 70% •FEV1 < 30% predicted or presence of respiratory failure or right heart failure Recommended Treatment •Long-term oxygen therapy •Treatment of complications •Consider surgical options Lancet 2003;362:1053-61 Surgical Treatments • Bullectomy: In carefully selected patients, this procedure is effective in reducing dyspnea and improving lung function (Evidence C) • Lung Volume Reduction Surgery • Lung Transplantation: In appropriately selected patients, improves quality of life and functional capacity (Evidence C). Criteria for referral: FEV1<35% predicted PaO2<55-60mm Hg, PaCO2>50 mm Hg, and secondary pulmonary hypertension Lung Volume Reduction Surgery • National Emphysema Treatment Trial Research Group • 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lungvolume reduction surgery or to receive continued medical treatment • Increases chance of improved exercise capacity but does not confer a survival advantage • Survival advantage for patients with predominantly upper-lobe emphysema and low base-line exercise capacity • A 70 year old male with GOLD stage III COPD has had increased shortness of breath, chest tightness, and a cough productive of yellow sputum. In the ER, T 98.9 HR 115 R 32 BP 120/80 Sats 89% on 2 L O2 (his home O2 requirement). He is using accessory muscles (sternocleidomastoids) and has thoracoabdominal dyssynchrony. He has very poor air movement bilaterally on lung exam. The rest of his exam is unremarkable. • How severe is his exacerbation? • What lab tests/x-rays should you order? • How should you treat him? Symptoms • Increased breathlessness, wheezing, chest tightness • Increased cough and sputum • Change in color and/or tenacity of sputum – An increase in sputum volume and purulence points to a bacterial cause • Nonspecific complaints: fever, malaise, fatigue, depression, confusion Assessment of severity of exacerbation • Peak flow <100 L/min or FEV1 <1.0 L indicates severe exacerbation • ABG • CXR • EKG • D-dimer, spiral CT • Sputum culture Manage Exacerbations: Key Points • Inhaled bronchodilators (Beta2-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocorticosteroids are effective for the treatment of COPD exacerbations (Evidence A). • 80% of AECB are infectious. Environmental factors and medication nonadherence are 20%. Manage Exacerbations: Key Points • Noninvasive intermittent positive pressure ventilation (NIPPV) in acute exacerbations improves blood gases and pH, reduces inhospital mortality, decreases the need for invasive mechanical ventilation and intubation, and decreases the length of hospital stay (Evidence A). NIPPV • Selection criteria: – Moderate to severe dyspnea with use of accessory muscles and paradoxical abdominal motion – Moderate to severe acidosis and hypercapnia – Respiratory frequency >25/min • Exclusion criteria: – – – – – – – – Respiratory arrest Cardiovascular instability Somnolence, impaired mental status, uncooperative patient High aspiration risk Viscous or copious secretions Recent facial or gastroesophageal surgery Craniofacial trauma Extreme obesity • He is admitted to 5500. How should he be treated? The nurse calls you because the patient is poorly responsive. T 98.6 HR 125 R 16 BP 110/65 Sats 92% on 50% face mask. Patient is barely arousable by sternal rub. What do you want to do now? • Which of the following is NOT true about this patient? • A. His inpatient mortality rate is 25%. • B. If he survives this hospitalization, he is likely to be readmitted within 6 months. • C. This is the ideal time to discuss code status with the patient’s family. • D. The patient’s five year mortality is 70%. • Retrospective study of 57 patients with COPD admitted to the ICU with a COPD exacerbation • 90% intubated • In-hospital mortality 24.5% • Median survival 26 months • Mortality rate at 5 years 69.6% • Chest 2005; 128:518-24