Disclosures Update on COPD & Asthma • No Pharma Disclosures • NHLBI - Asthma Clinical Research Network Michael C. Peters, M.D. MAS Division of Pulmonary & Critical Care Medicine Cardiovascular Research Institute • NHLBI – Severe Asthma Research Program University of California San Francisco UCSF Primary Care Medicine San Francisco, CA June 24, 2016 Update on the Management of COPD 1
To review COPD COPD • Pharmacologic Therapy: • COPD is a leading cause of death worldwide, and - More than symptoms - mortality is increasing - Decreasing exacerbations • COPD = Inflammatory Disease - Change natural history? • Smoking Cessation modifies natural history • Exacerbations are the major complication of COPD (lung function, mortality) • Associated with increased loss of lung function • O2 therapy • And Mortality • Pulmonary Rehab: reduces symptoms, depression, health care utilization; improves Q of L, • There are effective strategies for decreasing exercise exacerbations 2
Percent Change in Age-Adjusted Question #1: Death Rates (US, 1965–1998) Which of the following is NOT true? Proportion of 1965 Rate A. COPD mortality has plateaued 3.0 74% CHD All other B. Hospitalization for exacerbation Stroke Other CVD COPD causes 2.5 predicts mortality C. Most exacerbations are caused by 2.0 infection 17% 1.5 D. There are effective strategies for 4% 4% decreasing exacerbations 1.0 . . . . . . . . . . . . e t e a c e t r a l a a r 0.5 p x t s e s s a n r e h o o v i y f t i a t t n c i o b e l a i r f t t e f r a c e –59% –64% –35% +163% –7% o z a e m i x a l r e a 0.0 D t i t e p s P o r O s e o M h C H T 1965 – 1998 1965 – 1998 1965 – 1998 1965 – 1998 1965 – 1998 Hey Doc, Do I Have COPD???? Hey Doc, Do I Have COPD???? • CHRONIC Obstructive Pulmonary Disease • CHRONIC Obstructive Pulmonary Disease • NEED SPIROMETRY: FEV1/FVC < 0.70 • NEED SPIROMETRY: FEV1/FVC < 0.70 Simel and Rennie Simel and Rennie Evidence-based Clinical Diagnosis Evidence-based Clinical Diagnosis McGraw Hill, 2008 McGraw Hill, 2008 3
Respiratory Symptoms Smokers with Normal Pulmonary Prevalence of Symptoms and Risk of Respiratory Function Exacerbations Symptom Scores Woodruff PG et al. N Engl J Med 2016;374:1811-1821 Woodruff PG et al. N Engl J Med 2016;374:1811-1821 Risk Factors for COPD • No benefit of screening adults with no symptoms • No evidence that treating asymptomatic individuals prevents future symptoms, or reduces the subsequent decline in lung function. • Other: – Proteases/inflammation Anthonisen et al – Repetitive bacterial/viral infections JAMA 272:1497-505, 1994 – Genetics, especially α 1-antitrypsin Qaseen, Ann Int Med 155:179-91, 2011 deficiency USPTF JAMA 2016 NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease. April 2001; (Updated 2003). American Thoracic Society Statement Statement. Am J Respir Crit Care Med . 1995;152(suppl 5):S77-S120. 4
Give it to me Straight. Is it BAD? Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-Points (ECLIPSE) Eur Respir J 2008; 31:869-73 GOLD 2007 N = 2164 stable COPD N = 337 “Healthy Smokers” N = 245 Never Smokers FEV1/FVC < 0.70 GOLD 1: (Mild COPD) FEV1 > 80% predicted Characterized Extensively at: GOLD 2: (Moderate COPD) FEV1 50-80% predicted Baseline 3, 6, 12, 18, 24, 30, 36 months GOLD 3: (Severe COPD) FEV1 30-50% predicted GOLD 4: (Very Severe COPD) FEV1 <30% predicted GOLD Guidelines 2007 2007 Gold Guidelines Not Good Enough 2007 Gold Guidelines Not Good Enough Respir Res 2010; 11:122 Respir Res 2010; 11:122 Symptom Scores Agusti Respir Res 2010; 11:122 Agusti Respir Res 2010; 11:122 5
COPD Assessment : A New Model GOLD Guidelines 2015 When assessing risk, choose the highest risk according to GOLD grade or exacerbation history GOLD Guidelines 2015 GOLD Classification of Airflow Limitation 4 When assessing risk, choose the highest risk Exacerbation History ≥2 or (C) (D) according to GOLD grade or exacerbation history GOLD Classification of Airflow Limitation ≥1 leading 3 to hospital 4 admission Risk Exacerbation History ≥2 or Risk (C) (D) 2 1 ≥1 leading (no hospital 3 to hospital (A) (B) admission) Risk admission 1 Risk 0 2 1 (no hospital (B) mMRC 0-1 (A) admission) mMRC ≥ 2 CAT < 10 CAT ≥10 1 Symptoms 0 (mMRC or CAT score) mMRC 0-1 mMRC ≥ 2 Patient Characteristics Spirometric Exacerbations mMRC CAT CAT < 10 CAT ≥10 Symptoms Category Classification per year (mMRC or CAT score) A Low Risk, Less Symptoms GOLD 1-2 ≤1 0-1 <10 B Low Risk, More Symptoms GOLD 1-2 ≤1 ≥2 ≥10 C High Risk, Less Symptoms GOLD 3-4 ≥2 0-1 <10 D High Risk, More Symptoms GOLD 3-4 ≥2 ≥2 ≥10 Hospitalized Severe AECOPD and Mortality: Question #2: Severity of AECOPD Which of the Following Is the Best Predictor of a Future Acute Exacerbations 1- no AECOPD of COPD? 2- AECOPD ED 83% A. Spirometry B. Symptoms C. Smoking Status D. Socio-Economic Status N = 305 men with COPD 8% 4% 4% 0% x 5 years 3- AECOPD Hosp E. Prior Exacerbation History Spirometry 4- AECOPD Readmit Symptoms Smoking Status Socio-Economic Status Prior Exacerbation History Soler-Cataluna Thorax 2005 6
Predictors of Acute Exacerbations of Acute Exacerbations of COPD COPD • Some patients seldom exacerbate Number of Exacerbations • Some patients exacerbate frequently ≥ 2 vs. 0 1 vs. 0 Odds Ratio (95% CI) Odds Ratio (95% CI) • Best predictor of ≥2 AECOPD/year Exacerbation in Prior Year 5.7 (4.5-7.3) 2.2 (1.8-2.8) (“Frequent Exacerbator”) = previous FEV1 per 100ml decrease 1.1 (1.08-1.1) 1.1 (1.0-1.1) frequent exacerbations SGRC (symptom score) per 4 1.1 (1.0-1.1) 1.1 (1.0 – 1.1) points • Spirometry does not correlate well with GERD 2.1 (1.6-2.7) 1.6 (1.2-2.1) clinical features of disease WBC Count 1.1 (1-1.1) 1.1 (1.0-1.1) • “Frequent Exacerbator” is a stable phenotype Hurst NEJM 2010 COPD Exacerbations (AECOPD): The COPD Exacerbations • “ Exacerbations are to COPD what myocardial Major Complication of COPD infarctions are to coronary artery disease ” • Characterized by episodic increases in dyspnea, sputum production and cough • “ They are the acute, often trajectory- • 16 million office visits/year of a chronic disease ” changing, and sometimes deadly manifestations • 500,000 hospitalizations/year - Gerard J Criner, MD • 110,000 deaths/year Temple University School of Medicine Philadelphia, PA, USA • $18 billion in direct health care costs Mannino et al. MMWR Surveill Summ 2002; 51:1-16 NHLBI: http://www.nhlbi.gov/resources/docs/02_chtbk.pdf 7
Prevention of AECOPD Question #3: American College of Chest Physicians & Canadian Which of the Following DOES NOT Thoracic Society Guideline Reduce Acute Exacerbations of COPD? • PICO (population, intervention, comparator, outcome) A. Inhaled Corticosteroids 60% B. Long Acting Beta Agonist • Literature Search C. Long Acting Muscarinic 33% Agonists • Quality Assessment (AGREE II, DART) 7% D. Azithromycin 0% 0% n g E. EMR training s t d s i n i c i o i n . . y n . m r o a i e g c t A i o r s n r t i h • Grading Evidence (GRADEpro) o a r R c t a t M i e c i t z r B s A E o u g M C n d i g e t c n l A a t i • Recommendations (CHEST) h c g n n A I o g L n o L Criner et al. CHEST 147:894-942, 2015 Prevention of AECOPD Prevention of AECOPD Recommendations Recommendations Non-Pharmacologic Treatments/Vaccinations: Maintenance Inhaled Therapy: • LAMA vs PBO (Grade 1A) • Influenza Vaccine (Grade 1B) • LABA vs PBO (Grade 1B) • Pulmonary Rehab (Grade 1C) • LAMA vs LABA (Grade 1C) • Smoking Cessation (Grade 2C) • COMBO Therapy vs MonoTherapy (Grade • Pneumococcal Vaccine (Grade 2C) 1B,C) Mod-severe-very severe; recent AECOPD<4 weeks Criner et al. CHEST 147:894-942, 2015 Criner et al. CHEST 147:894-942, 2015 8
Prevention of AECOPD Recommendations Oral Therapy: • Macrolide (Grade 2A) (Frequent AECOPD despite Tx) • Systemic Corticosteroids (Grade 2B) (For AECOPD – prevent next 30 days) • Roflumilast (Grade 2A) (Chr Bronchitis, ≥1 AECOPD in year) • Do not use statins for AECOPD (Grade 1B) NEJM 365:689-98, 2011 Criner et al. CHEST 147:894-942, 2015 Macrolides Decrease AECOPD Rates of Acute Exacerbations of Chronic Obstructive Pulmonary Disease per The MACRO Study Person-Year, According to Study Group. (Azithromycin 250mg/day x 1 year) • NHLBI – COPD Clinical Research Network • N = 1130 • Moderately-severe COPD • “ Exacerbation Prone ” FEV 1 /FVC < 70%; FEV 1 <80% • Primary Outcome: Time to first AECOPD NEJM 365:689-98, 2011 Albert RK et al. NEJM 2011 9
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