Disclosures Update on COPD & Asthma No Pharma Disclosures - PDF document

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 • NHLBI – Severe Asthma Research Program Cardiovascular Research Institute University of California San Francisco • Parker B. Francis Foundation UCSF Primary Care Medicine San Francisco, CA May 27, 2016 Update on the Management of COPD 1

To review COPD COPD • Pharmacologic Therapy: • COPD is a leading cause of death worldwide, and ( “ it ’ s not just for symptoms anymore ” ) 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

Question #1: Question #1: Which of the following is NOT true? Which of the following is NOT true? 1. COPD mortality has 1. COPD mortality has plateaued plateaued 2. Hospitalization for 2. Hospitalization for exacerbation predicts exacerbation predicts mortality mortality 3. Most exacerbations are 3. Most exacerbations are caused by infection caused by infection 4. There are effective 4. There are effective strategies for strategies for decreasing decreasing exacerbations exacerbations Percent Change in Age-Adjusted Hey Doc, Do I Have COPD???? Death Rates (US, 1965–1998) • CHRONIC Obstructive Pulmonary Disease • NEED SPIROMETRY: FEV1/FVC < 0.70 Proportion of 1965 Rate • Physical Exam: 3.0 >90% Specificity CHD All other Stroke Other CVD COPD causes 2.5 Poor Sensitivity 2.0 • > 55 Pack Years • Wheezing on Auscultation 1.5 High Probability For COPD • Self-reported wheezing 1.0 Likelihood Ratio: 156 0.5 –59% –64% –35% +163% –7% Simel and Rennie 0.0 Evidence-based Clinical Diagnos is 1965 – 1998 1965 – 1998 1965 – 1998 1965 – 1998 1965 – 1998 McGraw Hill, 2008 3

Hey Doc, Do I Have COPD???? Respiratory Symptoms Smokers with Normal Pulmonary Function • CHRONIC Obstructive Pulmonary Disease • NEED SPIROMETRY: FEV1/FVC < 0.70 • Physical Exam: >90% Specificity Symptom Poor Sensitivity Scores • > 55 Pack Years • Wheezing on Auscultation High Probability For COPD • Self-reported wheezing Likelihood Ratio: 156 Simel and Rennie Evidence-based Clinical Diagnos is McGraw Hill, 2008 Woodruff PG et al. N Engl J M ed 2016;374:1811-1821 Prevalence of Symptoms and Risk of Respiratory Exacerbations • No benefit of screening adults with no symptoms • No evidence that treating asymptomatic individuals prevents future symptoms, or reduces the subsequent 20% decline in lung function. Anthonisen et al JAMA 272:1497-505, 1994 Qaseen, Ann Int Med 155:179-91, 2011 Woodruff PG et al. N Engl J M ed 2016;374:1811-1821 4

Give it to me Straight. Is it BAD? Risk Factors for COPD GOLD 2007 FEV1/FVC < 0.70 GOLD 1: (Mild COPD) FEV1 > 80% predicted • Other: GOLD 2: (Moderate COPD) FEV1 50-80% predicte d – Proteases/inflammation – Repetitive bacterial/viral infections GOLD 3: (Severe COPD) FEV1 30-50% predicte d – Genetics, especially a 1-antitrypsin GOLD 4: (Very Severe COPD) FEV1 <30% predicted deficiency NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease. April 2001; (Updated 2003). GOLD Guidelines 2007 American Thoracic Society Statement Statement. Am J Respir Crit Care Med . 1995;152(suppl 5):S77-S120. Evaluation of COPD Longitudinally to 2007 Gold Guidelines Not Good Enough Identify Predictive Surrogate End-Points (ECLIPSE) Respir Res 2010; 11:122 Eur Respir J 2008; 31:869-73 N = 2164 stable COPD N = 337 “Healthy Smokers” N = 245 Never Smokers Characterized Extensively at: Baseline 3, 6, 12, 18, 24, 30, 36 months Symptom Scores Agusti Respir Res 2010; 11:122 5

COPD Assessment : A New Model 2007 Gold Guidelines Not Good Enough When assessing risk, choose the highest risk GOLD Guidelines 2015 according to GOLD grade or exacerbation history of Airflow Limitation 4 Respir Res 2010; 11:122 (C) (D) ≥ 2 or Exacerbation History ≥ 1 leading 3 to hospital admission Risk Risk 2 1 GOLD Classification (no hospital (A) (B) admission) 1 0 mMRC 0-1 mMRC ≥ 2 CAT < 10 CAT ≥ 10 Symptoms (mMRC or CAT score) Patient Characteristics Spirometric Exacerbations mMRC CAT Category Classification per year 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 Agusti Respir Res 2010; 11:122 D High Risk, More Symptoms GOLD 3-4 ≥ 2 ≥ 2 ≥ 10 GOLD Guidelines 2015 GOLD Guidelines 2015 When assessing risk, choose the highest risk according to GOLD grade or exacerbation history of Airflow Limitation 4 Patient Characteristics Spirometric Exacerbations mMRC CAT (C) (D) ≥ 2 or Category Classification per year Exacerbation History ≥ 1 leading 3 A Low Risk, Less Symptoms GOLD 1-2 ≤ 1 0-1 <10 to hospital admission B Low Risk, More Symptoms GOLD 1-2 ≤ 1 ≥ 2 ≥ 10 Risk Risk 2 1 C High Risk, Less Symptoms GOLD 3-4 ≥ 2 0-1 <10 GOLD Classification (no hospital (A) (B) admission) D High Risk, More Symptoms GOLD 3-4 ≥ 2 ≥ 2 ≥ 10 1 0 mMRC 0-1 mMRC ≥ 2 CAT < 10 CAT ≥ 10 Symptoms (mMRC or CAT score) 6

Hospitalized Severe AECOPD and Mortality: Question #2: Severity of AECOPD Which of the Following Is the Best Predictor of a Future Acute 1- no AECOPD Exacerbations of COPD? 2- AECOPD ED 1. Spirometry 2. Symptoms 3. Smoking Status 4. Socio-Economic Status N = 305 men w ith COPD x 5 years 5. Prior Exacerbation History 3- AECOPD Hosp 4- AECOPD Readmit Soler-Cataluna Thorax 2005 Predictors of Acute Exacerbations of Acute Exacerbations of COPD COPD • Some patients seldom exacerbate • Some patients exacerbate frequently Number of Exacerbations ≥2 vs. 0 1 vs. 0 • Best predictor of ≥ 2 AECOPD/year Odds Ratio (95% CI) Odds Ratio (95% CI) (“Frequent Exacerbator”) = previous Exacerbation in Prior Year 5.7 (4.5-7.3) 2.2 (1.8-2.8) frequent exacerbations FEV1 per 100ml decrease 1.1 (1.08-1.1) 1.1 (1.0-1.1) SGRC (symptom score) per 4 1.1 (1.0-1.1) 1.1 (1.0 – 1.1) • Spirometry does not correlate well with points 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 7

COPD Exacerbations • “ Exacerbations are to COPD what myocardial infarctions are to coronary artery disease ” • “ They are the acute, often trajectory- changing, and sometimes deadly manifestations of a chronic disease ” - Gerard J Criner, MD Temple University School of Medicine Philadelphia, PA, USA COPD Exacerbations (AECOPD): The The Battle Plan. Major Complication of COPD • Characterized by episodic increases in • Prevent Acute Exacerbations dyspnea, sputum production and cough • Prevent Progressive Loss of Lung Function • 16 million office visits/year • Improve Symptoms • 500,000 hospitalizations/year • 110,000 deaths/year • $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 8

Question #3: Question #3: Which of the Following DOES NOT Which of the Following DOES NOT Reduce Acute Exacerbations of COPD? Reduce Acute Exacerbations of COPD? 1. Inhaled Corticosteroids 1. Inhaled Corticosteroids 2. Long Acting Beta Agonist 2. Long Acting Beta Agonist 3. Long Acting Muscarinic Agonists 3. Long Acting Muscarinic Agonists 4. Azithromycin 4. Azithromycin 5. EMR training 5. EMR training Prevention of AECOPD Prevention of AECOPD American College of Chest Physicians & Canadian Recommendations Thoracic Society Guideline Non-Pharmacologic Treatments/Vaccinations: • PICO (population, intervention, comparator, outcome) • Influenza Vaccine (Grade 1B) • Literature Search • Pulmonary Rehab (Grade 1C) • Smoking Cessation (Grade 2C) • Quality Assessment (AGREE II, DART) • Pneumococcal Vaccine (Grade 2C) Mod-severe-very severe; recent AECOPD<4 • Grading Evidence (GRADEpro) weeks • Recommendations (CHEST) Criner et al. CHEST 147:894-942, 2015 Criner et al. CHEST 147:894-942, 2015 9

Prevention of AECOPD Prevention of AECOPD Recommendations Recommendations Oral Therapy: Maintenance Inhaled Therapy: • Macrolide (Grade 2A) • LAMA vs PBO (Grade 1A) (Frequent AECOPD despite Tx) • LABA vs PBO (Grade 1B) • Systemic Corticosteroids (Grade 2B) • LAMA vs LABA (Grade 1C) (For AECOPD – prevent next 30 days) • Roflumilast (Grade 2A) • COMBO Therapy vs MonoTherapy (Grade (Chr Bronchitis, ≥ 1 AECOPD in year) 1B,C) • Do not use statins for AECOPD (Grade 1B) Criner et al. CHEST 147:894-942, 2015 Criner et al. CHEST 147:894-942, 2015 The MACRO Study (Azithromycin 250mg/day x 1 year) • NHLBI – COPD Clinical Research Network • N = 1130 • Moderately-severe COPD FEV 1 /FVC < 70%; FEV 1 <80% • “ Exacerbation Prone ” • Primary Outcome: Time to first AECOPD NEJM 365:689-98, 2011 NEJM 365:689-98, 2011 10