Asthma and COPD. Health Net Provider Educational Webinar

Asthma and COPD Health Net Provider Educational Webinar AstraZeneca 2015

Disclosures Presenters today are employed by Astra Zeneca and have nothing to disclose. This presentation is free from bias. 2

Objectives Today s Learning Objectives Understand the definition and underlying pathophysiology of both COPD and Asthma, as well as differentiate the clinical characteristics between each disease. Understand the role of spirometry to diagnose COPD and asthma and how that translates to patient symptoms. Know the changes that were implemented in the 2017 GOLD Report (Global Initiative for Chronic Obstructive Lung Disease) including changes to diagnosis, assessment and treatment recommendations of patients with COPD. Review the stepwise approach to treatment of patients with Asthma. Understand the emerging characteristics of eosinophilic asthma and the role of eosinophils in severe asthma 3

Asthma in Primary Care MAAZAP 3175617 Approved 09/15 AstraZeneca 2015

What Is Asthma? Asthma A chronic inflammatory disorder of the airways in which many cells and factors play a role 1 Inflammation results in 1 Recurrent symptoms Variable airflow obstruction Increase in existing bronchial hyperresponsiveness Asthma patients may have an accelerated decline in lung function and develop airflow limitation that is not fully reversible 2 5 1. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015; 2. GINA. Global Strategy for Asthma Management and Prevention. Updated 2015. Accessed August 20, 2015. AstraZeneca 2015

Every Day Due to Asthma in the US, an Estimated 70,000 absences from school and work 38,000 people experience an asthma attack 5500 ED visits 9 people die 1300 hospitalizations 6 ED = emergency department. Moorman JE et al. Vital Health Stat. 2012;3(35). Accessed August 20, 2015. AstraZeneca 2015

Key Indicators for a Diagnosis of Asthma Symptoms 1,2 Wheezing, shortness of breath (dyspnea), chest tightness, or cough Characteristics of asthma: >1 symptom Worse at night or in early morning Vary over time and in intensity Triggered by viral infections (colds), exercise, allergen exposure, changes in weather, laughter, or irritants such as car exhaust fumes, smoke, or strong smells Variable Expiratory Airflow Limitation 1 Spirometry is useful to establish a diagnosis of asthma 2 The greater the variations, or the more occasions excess variation is seen, the more confident the diagnosis 1 Confirm that FEV 1 /FVC is reduced (normally >0.75 0.80 in adults, >0.90 in children) when FEV 1 is low 1 7 FEV 1 = forced expiratory volume in 1 second; FVC = forced vital capacity. 1. GINA. Global Strategy for Asthma Management and Prevention. Updated 2015. Accessed August 20, 2015; 2. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. AstraZeneca 2015

Spirometry is Important in Asthma Useful in establishing a diagnosis and guiding management 1 Low FEV 1 is strongly predictive of risk for exacerbations 1,2 Important in assessing control 1 FEV 1 = forced expiratory volume in 1 second. 8 1. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. 2. Fuhlbrigge AL et al. J Allergy Clin Immunol. 2001;107:61-67. AstraZeneca 2015

Differentiating Asthma and COPD Asthma COPD Onset 1 Triggers 1 Early in life (often childhood) Allergens Midlife Cigarette smoke, occupational pollutants Symptoms 1 Variable Slowly progressive Clinical features 2,3 Episodic wheeze, chest tightness, cough, dyspnea Chronic dyspnea, cough, sputum, wheeze Inflammatory cells 1 Primarily eosinophils Primarily neutrophils 9 COPD = chronic obstructive pulmonary disease. 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD. Accessed August 20, 2015. 2. Currie GP, Legge JS. Chapter 3: Diagnosis. Blackwell Publishing; 2007:7-9. 3. Dewar M, Curry RW. Am Fam Physician. 2006;73:669-676. AstraZeneca 2015

Assessing Asthma Control 1,2 Symptom Control Frequency and intensity of daytime and nighttime symptoms Reliever use Activity limitation Work/school days missed Quality of life assessments Future Risk of Adverse Outcomes History of 1 exacerbations in the previous year Lung function (% predicted FEV 1 or FEV 1 /FVC) Inhaler technique and adherence Presence of blood eosinophilia Smoking 10 FEV 1 = forced expiratory volume in 1 second; FVC = forced vital capacity. 1. GINA. Global Strategy for Asthma Management and Prevention. Updated 2015. Accessed August 20, 2015; 2. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. AstraZeneca 2015

NAEPP. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Classifying Asthma Severity and Initiating Treatment in Youths 12 Years of Age and Adults Components of Severity Impairment Normal FEV 1 /FVC: 8-19 yr 85% 20-39 yr 80% 40-59 yr 75% 60-80 yr 70% Risk Symptoms Nighttime awakenings SABA use for symptom control (not prevention of EIB) Interference with normal activity Lung function Exacerbations requiring oral systemic corticosteroids Recommended Step for Initiating Treatment Intermittent 2 days/week 2x/month 2 days/week Persistent Mild Moderate Severe >2 days/week but not daily 3-4x/month >2 days/week but not daily and not >1x/day Daily >1x/week but not nightly Daily Throughout the day Often 7x/week Several times per day None Minor limitation Some limitation Extremely limited Normal FEV 1 between exacerbations FEV 1 >80% predicted FEV 1 /FVC normal 0-1/year FEV 1 >80% predicted FEV 1 /FVC normal FEV 1 >60% but <80% predicted FEV 1 /FVC reduced 5% 2/year FEV 1 <60% predicted FEV 1 /FVC reduced >5% Consider severity and interval since last exacerbation Frequency and severity may fluctuate over time for patients of any severity category Relative annual risk of exacerbations may be related to FEV 1 Step 1 Step 2 Step 3 Step 4 In 2-6 weeks, evaluate level of asthma control that is achieved and adjust therapy accordingly EIB = exercise-induced bronchospasm; FEV 1 = forced expiratory volume in 1 second; FVC = forced vital capacity; SABA = short-acting β 2 -adrenergic agonist. 11 Adapted from National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. AstraZeneca 2015

NAEPP. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Assessing Asthma Control and Adjusting Therapy in Youths 12 Years of Age and Adults Components of Control Well Controlled Not Well Controlled Very Poorly Controlled Symptoms 2 days/week >2 days/week but not daily Throughout the day Nighttime awakenings 2x/month 1-3x/week 4x/week Interference with normal activity None Some limitation Extremely limited Impairment Risk SABA use for symptom control (not prevention of EIB) FEV 1 or peak flow Validated questionnaires: ATAQ ACQ ACT Exacerbations requiring oral systemic corticosteroids Progressive loss of lung function Treatment-related adverse effects Recommended Action for Treatment 2 days/week >2 days/week Several times per day >80% predicted/ personal best 0 0.75 20 0-1/year 60-80% predicted/ personal best 1-2 1.5 16-19 2/year Consider severity and interval since last exacerbation Evaluation requires long-term follow-up <60% predicted/ personal best 3-4 N/A 15 Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk Maintain current step Regular follow-ups every 1-6 months to maintain control Consider step down if well controlled for 3 months Step up 1 step and reevaluate in 2-6 weeks For side effects, consider alternative treatment options Consider short course of OCS Step up 1-2 steps and reevaluate in 2 weeks For side effects, consider alternative treatment options 12 ACQ = Asthma Control Questionnaire; ACT = Asthma Control Test; ATAQ = Asthma Therapy Assessment Questionnaire; EIB = exercise-induced bronchospasm; OCS = oral systemic corticosteroids. Adapted from National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. AstraZeneca 2015

NAEPP. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma Stepwise Approach for Managing Asthma in Patients 12 Years Intermittent Asthma Persistent Asthma: Daily Medication Consult with asthma specialist if Step 4 care or higher is required Consider consultation at Step 3 Step 1 Preferred: SABA PRN Step 2 Preferred: Low-dose ICS (A) Alternative: Cromolyn (A), LTRA (A), Nedocromil (A), or Theophylline (B) Step 3 Preferred: Low-dose ICS + LABA (A) OR Medium-dose ICS (A) Alternative: Low-dose ICS + either LTRA (A), Theophylline (B), or Zileuton (D) Step 4 Preferred: Medium-dose ICS + LABA (B) Alternative: Medium-dose ICS + either LTRA (B), Theophylline (B), or Zileuton (D) Step 5 Preferred: High-dose ICS + LABA (B) AND Consider Omalizumab for Patients Who Have Allergies (B) Each Step: Patient education, environmental control, and management of comorbidities Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma Step 6 Preferred: High-dose ICS + LABA + OCS AND Consider Omalizumab for Patients Who Have Allergies Quick-relief Medication for All Patients SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20- minute intervals as needed. Short course of systemic oral corticosteroids may be needed Use of SABA >2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control and the need to step up treatment Step Up If Needed (first, check adherence, environmental control, and comorbid conditions) Assess Control Step Down If Possible (and asthma is well controlled 3 months) 13 EIB = exercise-induced bronchospasm; ICS = inhaled corticosteroid; LABA = long-acting β 2 -adrenergic agonist; LTRA = leukotriene receptor antagonist; OCS = oral systemic corticosteroids; SABA = short-acting β 2 -adrenergic agonist. Adapted from National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. NIH Publication 08-4051. Accessed August 20, 2015. AstraZeneca 2015

The Role of Eosinophils in Severe/Uncontrolled Asthma MAAZAP 3312907 Approved 12/16 AstraZeneca 2016 AstraZeneca 2016

Asthma Can Be Difficult To Treat The TENOR Study: A prospective, observational, 3-year study of US patients diagnosed with severe or difficult-to-treat asthma 4756 patients of all ages (severity per physician clinical assessment) Mild (3.2%) Moderate (48.4%) Severe (48.4%) 96% Considered Difficult To Treat Need for multiple drugs Frequency of exacerbations Severe exacerbations Inability to avoid triggers Complexity of treatment regimen 15 TENOR=The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens; US=United States. Dolan CM, et al. Ann Allergy Asthma Immunol. 2004;92:32-39. AstraZeneca 2016

Asthma Pathogenesis Allergen Dendritic cell / Macrophage Mast cell IgE Th2 Eosinophil Neutrophil B cell Mucus Plug Nerve activation Epithelial shedding Airway epithelial 16 Mucus hypersecretion Hyperplasia Vasodilation Angiogenesis Fibroblast Airway smooth muscle Plasma leakage Edema Bronchoconstriction IgE=immunogolublin E; Th2=T helper 2 cell. Hypertrophy/hyperplasia Figure adapted from Barnes PJ. Nat Rev Drug Discovery. 2004;3(10):831-844 and Gandhi NA et al. Nat Rev Drug Disc. 15;2016:35-50. Subepithelial fibrosis Sensory nerve activation Cholinergic reflex AstraZeneca 2016

Emerging Characteristics of Eosinophilic Asthma Can be late onset Elevated blood eosinophils! Equal gender distribution No or limited allergies to common allergens Risk of severe exacerbations Normal or moderately elevated IgE Rhinosinusitis with nasal polyps May be aspirin sensitive Low FEV 1 with persistent airflow limitation Dynamic hyperinflation and air trapping 17 FEV 1 =forced expiratory volume in 1 second; IgE=immunoglobulin type E. de Groot JC, et al. ERJ Open Research. 2015;1:00024-2015. AstraZeneca 2016

Peripheral Blood Eosinophil Levels Have Been Correlated With Both Asthma Severity and Control Severe Exacerbations Acute Respiratory Events Overall Asthma Control Peripheral Blood Eosinophils 201 300 cells per µl (n=25,882) 301 400 cells per µl (n=15,030) 401 500 cells per µl (n=8659) 501 600 cells per µl (n=4928) 601 700 cells per µl (n=2726) 701 800 cells per µl (n=1631) 801 900 cells per µl (n=947) 901 1000 cells per µl (n=1019) >1000 cells per µl (n=1019) 0.5 0.7 1.0 1.5 2.0 2.5 0.5 0.7 1.0 1.5 2.0 2.5 0.3 0.5 0.7 1.0 1.5 2.0 Adjusted RR a Adjusted RR a Adjusted OR a Severe Exacerbation an asthma-related hospitalization, attendance at an accident and emergency department, or a prescription for acute oral corticosteroids Acute Respiratory Event - defined more broadly as an asthma-related hospital attendance or admission or accident and emergency attendance, prescription for acute oral corticosteroids, or prescription for antibiotics in conjunction with an asthma-related primary care consultation Overall Asthma Control - the absence of any acute respiratory event (as defined above) or asthma-related outpatient department visit with an average daily dose of 200 μg or less salbutamol or 500 μg or less terbutaline 18 a Data from medical records of asthmatics aged 12 80 years with 2 years of continuous records, including 1 year before (baseline) and 1 year after (outcome) their most recent eosinophil count. Patients assigned to 9 eosinophil count categories compared with a reference category of 200 cells per μl or less (n=68,407). Adjusted for age, sex, body-mass index, smoking status, and Charlson comorbidity index score. RR=rate ratio; OR=odds ratio. Price DB, et al. Lancet Respir Med. 2015;3(11):849-858. AstraZeneca 2016

Increased Eosinophils in Asthma: Major Risk Factor for Exacerbations Historical Analysis of 130,547 Patients with Asthma Age (per year increase) Gender (F vs. M) Overweight vs. normal BMI Obese vs. normal BMI Smoker vs. non-smoker Ex-smoker vs. non-smoker Blood EOS >400/uL vs. 400/uL Anxiety/depression Diabetes (type 1 or 2) Eczema GERD Rhinitis Acetaminophen prescription Odds ratio (95% CI) p-value 1.007 (1.005-1.008) <0.001 1.21 (1.14-1.28) <0.001 1.08 (1.01-1.16) 0.028 1.17(1.09-1.24) <0.001 1.14 (1.06-1.22) <0.001 0.93 (0.88-0.99) 0.024 1.48 (1.39-1.58) <0.001 1.09 (1.04-1.15) 0.001 1.11 (1.05-1.17) <0.001 1.08(1.03-1.14) 0.003 1.12 (1.05-1.20) 0.001 1.10 (1.04-1.16) <0.001 1.23 (1.17-1.30) <0.001 Blood eosinophil >400/µL: Single best predictor of multiple exacerbations likelihood of 2 or more exacerbations by 1.5-fold 0.8 1.0 1.6 Decreasing likelihood Increasing likelihood of 2+ exacerbations Adapted from Price D et al. J Asthma Allergy 2016;9:1-12 GERD= Gastroesophageal reflux disease ; EOS= Eosinophils; BMI= Body mass index 19 Price D et al. J Asthma Allergy. 2016;9:1-12 AstraZeneca 2016

Summary: Increased Eosinophils in Asthma Elevated eosinophils were correlated with: Increased asthma severity 1,2 Worsening lung function 3-5 Exacerbation Risk 6,7 Lung function 3-5 Increased risk of exacerbations 6,7 Increased rates of hospitalizations and ED visits 6 16 1. Bousquet J et al. NEJM. 1990;323;1033-1039. 2. Louis R et al. Am J Respir Crit Care Med. 2000; 161; 9-16. 3. Broekema M et al. Respir Med. 2010; 104: 1254-1262. 4. Woodruff PG et al. J Allergy Clin Immunol. 2001;108:753-758. 5. McGrath KW et al. Am J Respir Care Med. 2012;185(6):612-619. 6. Zeiger RS, et al. J Allergy Clin Immunol Pract. 2014;2:741-750. 7. Price D et al. J Asthma Allergy. 2016;9:1-12. AstraZeneca 2016

Pathophysiology, Diagnosis and Management of Chronic Obstructive Pulmonary Disease (COPD) MAAZAP 3320501 Approved 1/17 2017 AstraZeneca

Contents Pathophysiology, Diagnosis and Management of COPD presentation 2017 GOLD Report slides 22 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD What Is COPD? COPD is... Preventable and treatable Associated with significant concomitant chronic diseases which increase its morbidity and mortality Characterized by persistent respiratory symptoms and airflow limitation that is: due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases 23 Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

COPD Is a Nationwide Problem In the United States, adults 18 years of age with COPD... are more likely to report being unable to work (24%) than adults who do not have COPD (5%) face activity limitations as a result of health problems (50%) compared with 17% of persons who do not have COPD Quartiles (%) 3.6% 5.0% require the use of special equipment (22%) for health problems compared with 7% of adults without COPD 5.1% 5.9% 6.0% 6.8% 6.9% 10.3% DC = District of Columbia PR = Puerto Rico GU = Guam Centers for Disease Control (CDC), Behavioral Risk Factor Surveillance System, 2013. cdc.gov/features/copd-burden. Accessed November 18, 2015. 24 Wheaton AG, et al. MMWR. 2015;64(11):289-295. 2017 AstraZeneca

COPD Arises From Damage and Inflammation in the Respiratory Tract Respiratory Anatomy Trachea Bronchi Bronchioles Alveoli 25 Image adapted from AstraZeneca website. Accessed June 2, 2015. 2017 AstraZeneca

Chronic Bronchitis and Airway Inflammation In healthy lungs, the airways are elastic and flexible With chronic bronchitis, airways can become swollen or thicker than normal Chronic bronchitis may cause increased mucus production Airways may become partially obstructed, making it harder to get air out of the lung. The resulting hyperinflation also makes inspiration difficult 26 NIH. National Heart, Lung, and Blood Institute. COPD Learn More Breathe Better. NIH.gov website. http://www.nhlbi.nih.gov/files/docs/public/lung/copdpatient.pdf. Accessed December 17, 2015. Images adapted from AstraZeneca website. Accessed December 17, 2015. 2017 AstraZeneca

Emphysema Is Caused by Damage to the Alveoli Walls Healthy alveoli are elastic and capable of springing back to their original size after active inspiration Emphysema involves damage to the walls of the alveoli In emphysema, alveoli lose their elasticity, which impairs natural passive exhalation, resulting in trapping of air and hyperinflation 27 American Thoracic website. Accessed December 17, 2015. Images adapted from AstraZeneca website. Accessed December 17, 2015. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Key Indicators for a Diagnosis of COPD Symptoms and Past Medical History Dyspnea progressive, worse with exercise, persistent Chronic cough may be intermittent and unproductive, recurrent wheeze Chronic sputum production any pattern of chronic sputum production may indicate COPD Recurrent lower respiratory tract infections History of Risk Factors Host factors (genetic, congenital/developmental) Tobacco smoke Smoke from home cooking/heating fuels Occupational dusts, vapors, fumes gases or chemicals Family History of COPD and/or Childhood Factors AND Airflow Limitation Post-bronchodilator FEV 1 /FVC <0.70* GOLD recommends active casefinding: i.e. Performing spirometry in patients with symptoms and/or risk factors, but not screening spirometry 28 *Required for the diagnosis of COPD. FEV 1 =forced expiratory volume in 1 second; FVC=forced vital capacity. Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Use Spirometry to Confirm COPD Diagnosis 1 Post-bronchodilator FEV 1 /FVC <0.70 indicates COPD diagnosis Spirometry Normal Trace Spirometry Obstructive Disease 5 5 Volume, liters 4 3 2 1 FEV 1 = 4 L FVC = 5 L FEV 1 /FVC = 0.8 Volume, liters 4 3 2 1 FEV 1 = 1.8 L FVC = 3.2 L FEV 1 /FVC = 0.56 0 1 2 3 4 5 6 Time, Seconds 0 1 2 3 4 5 6 Time, Seconds FEV 1 : Amount of air exhaled in the first second during the FVC maneuver 2 FVC: Total amount of air a person can forcibly exhale after maximum inhalation 2 FEV 1 = forced expiratory volume in one second; FVC = forced vital capacity Adapted from Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD. 29 1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2. Miller MR,et al. Eur Respir J. 2005;26:319-338. 2017 AstraZeneca

Understanding Lung Volume Measurements in Patients With COPD 1,2 Volume TLC VC Maximum inspiration V T Maximum exhalation IC IC FRC IC FRC RV Normal COPD 30 IC = inspiratory capacity; TLC=total lung capacity; VC=vital capacity; V T =tidal volume; RV=residual volume; FRC=functional residual capacity. 1. Ferguson GT. Proc Am Thorac Soc. 2006;3:176-179. 2. Sutherland ER, Cherniack RM. N Engl J Med. 2004;350:2689-2697. 2017 AstraZeneca

COPD Exacerbations: Risk Factors and Impact Risk factors z Impact Frequent past exacerbations Severity of FEV 1 impairment Chronic bronchial mucus hypersecretion Daily cough and wheeze Increased age Persistent symptoms of chronic bronchitis Comorbid conditions, mainly cardiovascular disease More rapid decline of FEV 1 Increased dyspnea Greater decline in health status Increased mortality 31 Anzueto, A. Impact of exacerbations on COPD. Eur Respir Rev. 2010;19:116,113 118. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD The Refined ABCD Assessment tool (steps 1 and 2) Spirometrically Confirmed Diagnosis Assessment of Airflow Limitation (FEV 1 % predicted) Post-bronchodilator FEV 1 /FVC < 0.7 GOLD 1 80% GOLD 2 50% - 79% GOLD 3 30% - 49% GOLD 4 < 30% 32 Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD The Refined ABCD Assessment tool (step 3) Exacerbation history Assessment of symptoms/risk of exacerbations 2 or 1 leading to hospital admission C D 0 or 1 (not leading to hospital admission) A B mmrc 0-1 CAT < 10 Symptoms mmrc 2 CAT 10 33 Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Exacerbations GOLD defines an exacerbation as an acute worsening of respiratory symptoms that result in additional therapy Exacerbations are classified as: Mild: Moderate: Severe: Treated with SABDs only Treated with SABDs plus antibiotics and/or oral corticosteroids Patient requires hospitalization or visits the emergency room; + acute respiratory failure 34 SABD = Short-acting bronchodilator. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Goals of COPD Management Reduce Symptoms Reduce Risk Relieve symptoms Improve exercise tolerance Improve health status AND Prevent disease progression Prevent and treat exacerbations Reduce mortality 35 Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

How Can We Improve COPD Management? COPD remains underdiagnosed 1 Awareness of COPD guidelines suboptimal 2 Spirometry used inconsistently 2 Mortality increasing among women 3 Presentation in the fifth decade of life, 4 though early symptoms may be missed 2 Accurate diagnosis and treatment may lead to better outcomes 5 Appropriate treatment may reduce symptoms and exacerbations, and improve health status 5 Spirometry is key to diagnosis, assessment of severity, and progression of COPD 5 Consideration must also be given to symptom evaluation, exacerbation risk and comorbidities 5 Education represents an opportunity to improve outcomes for COPD patients 2,5 36 1. Mannino DM, et al. MMWR Surveillance Summary. 2002;51:1-16. 2. Yawn BP, Wollan PC. Int J COPD. 2008;3:311-317. 3. Deaths from chronic obstructive pulmonary disease United States, 2000-2005. MMWR Morb Mortal Wkly Rep. 2008;57:1229-1232. 4. American Association for Respiratory Care. Confronting COPD in America: Executive Summary. http://c.aarc.org/resources/confronting_copd/exesum.pdf. Accessed December 17, 2015. 5. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Nonpharmacologic Management of COPD Patient Group Essential Recommended Depending on Local Guidelines A Smoking cessation (can include pharmacologic treatment) Physical activity Flu vaccination Pneumococcal vaccination B-D Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Flu vaccination Pneumococcal vaccination 37 Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. 2017 AstraZeneca

Global Strategy for the Diagnosis, Management, and Prevention of COPD Pharmacologic Treatment Algorithms Group C Further exacerbation(s) Group A LAMA + LABA LAMA LABA + ICS Group D Consider PDE-4 inhibitor if FEV 1 < 50% pred. and patient has chronic bronchitis Group B Further exacerbation(s) LAMA + LABA + ICS Further exacerbation(s) LAMA LAMA + LABA Consider macrolide (if former smokers) Persistent symptoms / Further exacerbation(s LABA + ICS Continue, stop or try alternative class of bronchodilator Evaluate effect A bronchodilator LAMA + LABA Persistent symptoms long-acting bronchodilator (LABA or LAMA) 38 SABA = short-acting β 2 -agonist; SAMA = short-acting muscarinic antagonist; LABA = long-acting β 2 -agonist; LAMA = long-acting muscarinic antagonist; ICS = inhaled corticosteroid; PDE-4 = phosphodiesterase-4. Adapted from Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Accessed January 6, 2017. Preferred treatment 2017 AstraZeneca

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