Objectives. The Impact of COPD in the United States. Risk Factors for COPD. Pathophysiology of COPD

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Objectives Upon completion of this activity, participants will be able to: Identify diagnostic challenges in Understand evidence-based guidelines recommendations for assessment of Recognize appropriate non-pharmacologic and pharmacologic management strategies of GOLD: Global Initiative for Chronic Obstructive Lung Disease GOLD definition of 1 Common, preventable, treatable partially reversible Characterized by persistent airflow limitation Usually progressive and disabling Associated with enhanced chronic inflammatory response in airways/lung to noxious particles or gases is heterogeneous 2 Multiple risk factors, phenotypes, comorbidities and comorbidities contribute to severity 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. www.goldcopd.org. 2. Goh F et al. Expert Rev RespirMed. 2013;7(6):593-605. The Impact of in the United States In 2010, accounted for 1 10.3 million physician office visits/y 1.5 million ED visits 699,000 hospital discharges Costly 2 Direct: $27 billion/y Indirect: $20 billion/y 3rd leading cause of death 3 4th leading cause of hospital readmissions 4 1. Ford ES et al. Chest. 2013;144(1):284-305. 2.. Morbidity & Mortality 2012 Chart Book. www.nhlbi.nih.gov/resources/docs/2012_chartbook_508. pdf. 3. HeronM. Natl Vital Stat Rep. 2012;60(6):1-94. 4. Jencks SF et al. N Engl J Med. 2009; 360:1418-1428. Risk Factors for Exposure to inhaled particles: Tobacco smoke (active and passive) Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings Outdoor air pollution Susceptibility genes Poor lung growth and development Oxidative stress Female gender Age Respiratory infections Low socioeconomic status Poor nutrition Co-morbidities Emphysema and Small Airways Disease Contribute to Total Airflow Limitation in Pathophysiology of Normal Airway held open by alveolar attachments (elastin fibers) Disrupted alveolar attachments (emphysema) Mucosal inflammation, fibrosis Mucus hypersecretion and inflammatory exudate Airway obstructed by: Loss of alveolar attachments Mucosal inflammation and fibrosis Luminal obstruction with inflammatory exudate and mucus Hyperinflation, central to the pathophysiology of (ie, increased airway resistance), correlates more directly with patient-reported outcomes Hypoxemia Anxiety Patientreported outcomes Tachypnea Dyspnea Airflow obstruction Air trapping Hyperinflation Ventilatory requirement Activity limitation Poor health-related quality of life Deconditioning Sturton G et al. Trends Pharmacol Sci. 2008;29:340-345; Hogg JC et al. N Engl J Med. 2004;350:2645-2653. Cooper CB. Respir Med. 2008;20:1-10.

Improving Outcomes in Early diagnosis and accurate assessment Identifying patients at risk Using appropriate diagnostic approaches, ruling out other mimickers Key Indicators for Diagnosis Consider a diagnosis of, and perform spirometry, if any of these indicators * are present in an individual >40 years of age Exertional dyspnea Chronic cough Chronic sputum production History of exposure to risk factors (eg, tobacco smoke) Spirometry is required to make the diagnosis Post-bronchodilator FEV 1 /FVC <0.70 confirms persistent airflow limitation and diagnosis Rice K, et al. Clin Chest Med. 2014;35(2):337-351; Decramer M, et al. Respir Med. 2011;105(11):1576-1587. *These indicators are not diagnostic in themselves, but the presence of multiple key indicators increases the probability of a diagnosis. FEV 1 = forced expiratory volume in 1 second; FVC = forced vital capacity Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2009. http://www.goldcopd.org/uploads/users/files/gold_report2014_feb07.pdf. Natural History of Significant Drops in Lung Function Are Often Required for Patients to Become Severely Symptomatic PT # 1 59 y FEV1: 28 % PT # 2 63 y FEV1: 33 % PT # 3 70 y FEV1: 35 % PT # 4 72 y FEV1: 34 % MRC: 2/4 MRC: 2/4 MRC: 3/4 MRC: 4/4 FEV 1 (% predicted at age 25 years) 100 75 50 25 Dyspnea, Cough Exercise Intolerance 0 25 50 75 Hospitalizations Systemic Effects Respiratory Failure Pulm Hypertension PaO2: 70 mmhg 6MWD: 540 mt BMI: 30 PaO2: 57 mmhg PaO2: 66 mmhg 6MWD: 348mt 6MWD: 230 mt BMI: 21 BMI: 34 Heterogeneity PaO2: 60 mmhg 6MWD: 140 mt BMI: 24 Age (years) Patient assessment criteria* Assessment of Assessment of : Symptoms 2010 Airflow Limitation Spirometry for diagnosis and assessment 2016 Symptoms Validated patient questionnaires (mmrc and CAT) Exacerbation Risk History of exacerbations or spirometric classification Grade Description of Breathlessness 0 I only get breathless with strenuous exercise 1 I get short of breath when hurrying on level ground or walking up a slight hill 2 On level ground, I walk slower than people of the same age because of breathlessness, or have to stop for breath when walking at my own pace 3 I stop for breath after walking about 100 yards or after a few minutes on level ground 4 I am too breathless to leave the house or I am breathless when dressing *Pharmacological management of should also include an assessment of potential patient comorbidities mmrc: Modified Medical Research Council Dyspnea Scale CAT: Assessment Test 1.Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease 2010. 2.Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease 2013. Modified Medical Research Council Dyspnea Score 0 1 Symptoms 2 3 4 GOLD Website. http://www.goldcopd.com. Updated December 2011 More Severe

Assessment Test (CAT) Assessment of : Lung Function The frequent exacerbator phenotype : Parameters associated with exacerbation in year 1 (multivariate analysis) In patients with post-bronchodilator FEV 1 /FVC < 0.70: GOLD 1: Mild FEV 1 > 80% predicted GOLD 2: Moderate 50% < FEV 1 < 80% predicted GOLD 3: Severe 30% < FEV 1 < 50% predicted GOLD 4: Very Severe FEV 1 < 30% predicted *Based on Post-Bronchodilator FEV 1 Odds Ratio for 2 vs 0 Analysis by GOLD Stage showed similar results: The best predictor of future exacerbation is a history of previous exacerbations. P=0.002 Exacerbation During Previous Year FEV 1 (per 100mL decrease) SGRQ score (per 4-point increase) Positive history of reflux or heartburn White Cell Count (per increase of 1000/mL) GOLD Website. http://www.goldcopd.com. Updated December 2011 Hurst JR, et al. New Engl J Med. 2010;363:1128-38. Risk GOLD 2016: Combined Assessment (GOLD Classification of Airflow Limitation) Assessment Using Symptoms, Breathlessness, Spirometric Classification, and Risk of a 4 3 2 C High risk, Less symptoms A D High risk, More symptoms a When assessing risk, choose the highest risk according to GOLD grade or exacerbation history. B 2 or 1 leading to hospital admission 1 (not leading to hospital admission) 1 Low risk, Less symptoms Low risk, More symptoms 0 CAT < 10 CAT 10 Symptoms mmrc 0 1 mmrc 2 Breathlessness Risk (/Year) Lung cancer Pulmonary hypertension Anemia Cachexia Diabetes Metabolic syndrome Kao C, Hanania NA. in: Crapo J, ed. Philadelphia, PA: Current Medicine Group;2008. Comorbidities of Anxiety, depression Cardiovascular disease Peripheral muscle wasting and dysfunction Osteoporosis Peptic ulcers GI complications These comorbid conditions may influence mortality and hospitalizations; the patient should be assessed for them routinely and treated appropriately.

Improving Outcomes in Goals of Management Early diagnosis and accurate assessment Identifying patients at risk Using appropriate diagnostic approaches, ruling out other mimickers Implementing optimal management Reducing exposures to risk factors and triggers Non-pharmacological approaches Pharmacological treatments Airflow Limitation Symptom Burden Functional Limitations Improve Lung Function Slow FEV1 Decline Improve Symptoms Prevent and Manage Improve Health Status and Exercise Tolerance Reduce Hospital Admissions and Mortality Rice K, et al. Clin Chest Med. 2014;35(2):337-351; Decramer M, et al. Respir Med. 2011;105(11):1576-1587. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. www.goldcopd.org. Nonpharmacologic Therapy To Manage Smoking Cessation Patient Education Vaccination Patient Group Non-pharmacological Options for A Low risk, fewer symptoms B Low risk, more symptoms C High risk, fewer symptoms D High risk, more symptoms Description GOLD 1-2 <1 Exacerbation mmrc 0-1 or CAT <10 GOLD 1-2 <1 Exacerbation mmrc >2 or CAT >10 GOLD 3-4 >2 mmrc 0-1 or CAT <10 GOLD 3-4 >2 mmrc >2 or CAT >10 Oxygen Therapy Pulmonary Rehabilitation Surgical and Nonsurgical Alternatives Essential Smoking cessation for all patients who smoke The key intervention for smokers Can include pharmacologic treatment Pulmonary rehabilitation Recommended Physical activity Depending on local guidelines Influenza vaccination Pneumococcal vaccination Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2008. Adapted from Global Initiative for Chronic Obstructive Lung Disease; (GOLD) 2014. www.goldcopd.org. Exercise Training Involves the measurement of a number of physiologic variables, including maximum oxygen consumption, maximum heart rate, and maximum work performed Components of Pulmonary Rehabilitation Programs Pulmonary Rehabilitation Programs Nutrition Counseling Important determinant of symptoms, disability, and prognosis in ; a reduction in BMI is an independent risk factor for mortality in patients with Assessment and Follow-up Education Specific contributions of education to the improvements seen after pulmonary rehabilitation remain unclear Outcomes of Pulmonary Rehab in Reduces dyspnea Improves deconditioning, muscle fatigue Increases exercise capacity Improves quality of life Improves depression Reduces acute exacerbations Reduces hospitalizations May reduce mortality Does not improve PFTs or ABGs BMI=body mass index. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2009. http://www.goldcopd.org. Accessed April 9, 2010. 1 British Thoracic Society. Thorax. 2001; 56:827-34. 2 American Thoracic Society. Am J Respir Crit Care Med. 1999;159:1666-82. 3 Guell R, et al. Chest. 2000;117:976-83. 4 Saey D, et al. Am J Respir Crit Care Med. 2003;168:425-30. 5 Casaburi R. Am J Respir Crit Care Med. 2003;168:409-10. 6 Casaburi R, et al. Am J Respir Crit Care Med. 1997;155:1541-51. 7 Griffiths TL, et al. Lancet. 2000;355:362-8. 8 Cote CG, et al. Am J Respir Crit Care Med. 2003;167:A38.

Pharmacological Management of Guideline-recommended treatment Improves lung function Minimizes symptoms Improves QoL Prevents exacerbations Wide variety of options including new agents Appropriate treatment selection hinges on GOLD staging Before stepping up/modifying treatment, re-evaluate Treatment goals Clinical phenotype Comorbidities Adherence Pharmacological Agents Approved in the U.S. Short-acting β-agonists (SABA) Albuterol Pirbuterol Levalbuterol Bronchodilators Anticholinergic (SAMA) Ipratropium Long-acting β-agonists (LABA) Salmeterol Formoterol Arformoterol Indacaterol Oladaterol Anticholinergic (LAMA) Tiotropium Aclidinium Umeclidinium Glycopyrrium LABA +LAMA Umeclidinium +Vilanterol Tiotropium + Oladaterol Glycopyrrinium _Indacaterol Theophylline Anti-Inflammatory ICS+LABA Fluticasone + Salmeterol Budesonide +Formoterol Fluticasone Fuorate +Vilanterol PDE-4 Inhibitors Roflumilast Systemic Steroids Prednisone Methylprednisolone Treatment Options Rationale for Early Treatment in The effect of treatment on lung function may be more marked in patients who are younger and in those with less severe disease 1-4 Lung function deteriorates more rapidly during the less severe, early stages of 3 LABA and LAMA are recommended initial maintenance therapy for patients who are symptomatic but at low risk of exacerbations 5 Lack of data in treatment-naïve patients with mild or moderate airflow limitation Adapted from: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease 2014. 1 Troosters T, et al. Eur Respir J. 2010;36(1):65-73; 2 Celli B, et al. Am J Respir Crit Care Med. 2009;180(10):948-955; 3 Decramer M, Cooper CB. Thorax. 2010;65(9):837-841; 4 Morice AH, et al. Respir Med. 2010;104(11):1659-1667; 5 GOLD 2011. www.goldcopd.com. Improving Outcomes in Early diagnosis and accurate assessment Identifying patients at risk Using appropriate diagnostic approaches, ruling out other mimickers Implementing optimal management Reducing exposures to risk factors and triggers Non-pharmacological approaches Pharmacological treatments Incorporating self-management skills through education and collaboration with a health care team Improve adherence Summary continues to be a major public health problem Improving outcomes in is dependent on: Early diagnosis and accurate assessment Implementing optimal management Incorporating self-management skills through education and collaboration with a health care team Rice K, et al. Clin Chest Med. 2014;35(2):337-351; Decramer M, et al. Respir Med. 2011;105(11):1576-1587.