Implementing GOLD COPD Guidelines

Transcription

1 Implementing GOLD COPD Guidelines Nicola A. Hanania, MD, MS, FCCP, FERS Associate Professor of Medicine Pulmonary and Critical Care Medicine Director, Airways Clinical Research Center

2 Disclosure Information Advisor/ Consultant: - Roche/ Genentech, AstraZeneca, GSK, BI, Sunovion, Novartis, Mylan, Sanofi/Regeneron Research grant support (to institution): - NHLBI, ALA - GSK, BI, Roche/Genentech, Sunovion, Mylan, AstraZeneca

3 GOLD: Global Initiative for Chronic Obstructive Lung Disease 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 COPD is heterogeneous 2 Multiple risk factors, phenotypes, comorbidities Exacerbations and comorbidities contribute to severity 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) Goh F, et al. Expert Rev Respir Med. 2013;7(6):

4 Burden of COPD in the US 1 in 5 Americans has COPD 16 million people are diagnosed Total costs from hospitalization and absenteeism estimated at $36 Billion COPD exacerbations account for >70% of total costs 13 million office visits/y due to exacerbations Disproportionately affects individuals of lower socioeconomic status Ford, et al. Chest 2013;144:305 Ford, et al. Chest 2013;143:1395

5 COPD is Underdiagnosed Roughly half of those in the US with COPD are undiagnosed ~15 million Americans Haroon, et al. Int J COPD 2015;10(1):1711

6 COPD National Action Plan The first-ever blueprint for a multifaceted, unified fight against the disease. Developed at the request of Congress with input from the broad COPD community. Provides a comprehensive framework for action by those affected by the disease and those who care about reducing its burden. #COPDActionPlan

7 What do we know now? Factors that Influence Disease Progression 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 - A1AD - CHRNA3/CHRNA5/IREB2 region on chromosome 15 - HHIP, and FAM13A Oxidative stress Female gender Age Respiratory infections Low socioeconomic status Poor nutrition Poor lung growth and development

8 Early-Life Origins of COPD M.J. McGeachie et al. N Engl J Med 2016;374: FD Martinez, N Engl J Med 2016;375: Factors associated with reduced lung growth: Lower baseline FEV1 Smaller bronchodilator response AHR at baseline Male sex

9 Inflammatory and Cellular Mechanisms in COPD due to Cigarette Smoking Chung KF, et al. Eur Respir J. 2008;31:

10 Oxidative Stress is Central to the Destruction of Pulmonary Tissue Auto Barnes PJ. Clin Chest Med 35 (2014) 71 86

11 COPD is a Multicomponent Disease Mucus hypersecretion Reduced mucociliary transport Mucosal damage Increased numbers of inflammatory cells/ activation: CD8+ T-lymphocytes Monocytes/ macrophages Neutrophils Mast cells Airflow Elevated inflammatorylimitation mediators: IL-8, TNF-, LTB-4, and oxidants Protease/anti-protease imbalance Mucociliary dysfunction Airway inflammation Structural changes Systemic component Loss of alveolar attachments Loss of elastic recoil Increased smooth muscle contraction Goblet cell hyperplasia/ metaplasia Mucous gland hypertrophy Increased smooth muscle mass Airway fibrosis Alveolar destruction Poor nutritional status Reduced BMI Impaired skeletal muscle Weakness Wasting

12 COPD Diagnosis Consider COPD in patients with any symptoms and history of exposure to risk factors SYMPTOMS SYMPTOMS Persistent shortness of breath Chronic cough Chronic sputum production Wheezing RISK FACTORS RISK FACTORS Tobacco smoke Indoor/outdoor air pollution Occupational pollutants Family history Age >40 y Spirometry is required to make diagnosis Postbronchodilator FEV 1 /FVC <.70 confirms presence of persistent airflow limitation * *Postbronchodilator FEV 1 /FVC measured min after 2-4 puffs of a short-acting bronchodilator FEV 1, forced expired volume in 1 second; FVC, forced vital capacity Global Initiative for Chronic Obstructive Lung Disease (GOLD)

13 Assessment of COPD Degree of airflow limitation (using spirometry) Symptoms Risk of exacerbations (estimated by history of COPD exacerbations) Comorbidities The goals of COPD assessment are to determine disease severity, its impact on patient health status, and the risk of future events (eg, exacerbations, hospital admissions, death) in order to guide therapy

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15 GOLD Staging System: Spirometry Very severe FEV 1 <30% predicted GOLD Grade 4 GOLD Grade 1 Mild FEV 1 80% predicted Severe 30% FEV 1 <50% predicted GOLD Grade 3 GOLD Grade 2 Moderate 50% FEV 1 <80% predicted Postbronchodilator FEV 1 /FVC <.70 Confirms presence of persistent airflow limitation Supports diagnosis of COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD). GOLD COPD web site. Accessed June 18, 2015.

16 Assessment of COPD: Symptoms 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 Modified Medical Research Council Dyspnea Score 0 1 Symptoms More Severe GOLD Website.

17 COPD Assessment Test (CAT)

18 Assessment of Exacerbation Risk COPD exacerbations are defined as an acute worsening of respiratory symptoms that result in additional therapy. Classified as: Mild (treated with SABDs only) Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or Severe (patient requires hospitalization or visits the emergency room). Severe exacerbations may also be associated with acute respiratory failure.

19 Frequent Exacerbations Drive Disease Progression Patients with frequent exacerbations Lower quality of life Increased mortality rate Increased inflammation Increased risk of recurrent exacerbations Faster disease progression Increased likelihood of hospitalization Wedzicha JA & Seemungal TA. Lancet 2007;370: ,; Donaldson GC & Wedzicha JA. Thorax 2006;61:

20 2017 GOLD Assessment Tool Spirometrically confirmed diagnosis Assessment of airflow limitation Assessment of symptoms/risk of exacerbations Exacerbation history Postbronchodilator FEV 1 /FVC < 0.7 FEV 1 (% predicted) GOLD 1 80 GOLD GOLD GOLD 4 < 30 2 or 1 leading to hospital admission 0 or 1 (not leading to hospital admission) C A D B From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available at: mmrc 0-1 CAT < 10 mmrc 2 CAT 10 Symptoms

21 Comorbidities of COPD Lung cancer Anxiety, depression Pulmonary hypertension Cardiovascular disease Anemia Peripheral muscle wasting and dysfunction Diabetes Metabolic syndrome Osteoporosis Peptic ulcers GI complications Cachexia Kao C, Hanania NA. in: Crapo J, ed. Philadelphia, PA: Current Medicine Group;2008.

22 Exploring the Links Between COPD and Its Comorbidities Risk Factors COPD Mechanisms Comorbidities Outcomes Smoking and lifestyle factors Genetic susceptibility Chronic airway infection Acute exacerbations Airway and systemic inflammation Lung hyperinflation and endothelial dysfunction Oxidative stress Ischemic heart disease Stroke and heart failure Hypertension and diabetes Muscle weakness and osteoporotic fractures Depression Worse symptoms Worse health status Reduced activity Reduced survival Patel AR, Hurst JR. Expert Rev Respir Med. 2011;5(5):

23 The Challenge: COPD is a Heterogenous Disease Hyperinflation Undernourished Cardiac disease Emphysema predominant Osteoporosis Airway predominant Hypercapnia Pulmonary fibrosis Hypoxemia Frequent Exacerbator Deconditioned

24 Why Phenotype COPD Patients? A phenotype relates to a single or combination of attributes that describe differences between individuals Enhances our understanding of the disease process, treatment and outcomes Allows for classification of patients into distinct therapeutic and prognostic subgroups Allows for enrichment of clinical trial population Improves outcomes

25 Phenotypic Dimensions Physiological Airflow limitation Rapid decliner BD-responsiveness Hyperresponsiveness Gas exchange: PaO2, PaCO2, DLCO Exercise tolerance Hyperinflation Pulmonary hypertension Radiologic/ Structural Emphysema Chronic bronchitis Bronchiectasis Fibrosis Clinical Chronic bronchitis Asthma/COPD overlap Exacerbations Dyspnea HRQoL ICS-responsive Non-smokers Systemic effects/ Comorbidities Nutritional status Skeletal (respiratory and peripheral) muscles Exercise capacity Cardiovascular disorders Local and Systemic inflammation Local inflammation: inflammatory markers or cells in sputum or lung tissue Systemic inflammation: inflammatory markers or cells in blood or serum Proteolysis Oxidative stress Vascular remodeling

26 COPD Phenotypes Disease attributes that describe the diverse symptoms and outcomes of patients Frequent Exacerbations Systemic Inflammation Chronic Hypoxemia Exercise/ Activity Intolerance/ Hyperinflation Chronic Cough and Sputum COPD Chronic Respiratory Failure Comorbidities Cardiac, Nutritional Radiologic Airway (CB, bronchiectasis), Emphysema Asthma COPD Overlap Syndrome (ACOS) Symptom Burden Chen X et al. Front. Med. 2013;7(4): Oga T et al. Chest. 2005;128: Westwood M et al. Respir Res. 2011;12:40.

27 Clinical Course of COPD Hyperinflation, central to the pathophysiology of COPD (ie, increased airway resistance), correlates more directly with patient-reported outcomes COPD Hypoxemia Airflow obstruction Exacerbations Tachypnea Air trapping Ventilatory requirement Anxiety Hyperinflation Deconditioning Dyspnea Patientreported outcomes Cooper CB. Respir Med. 2008;20:1-10. Poor health-related quality of life Activity limitation

28 Goals of Management Airflow Limitation Improve Lung Function Slow FEV1 Decline Symptom Burden Improve Symptoms Exacerbations Functional Limitations Prevent and Manage Exacerbations Improve Health Status and Exercise Tolerance Reduce Hospital Admissions and Mortality Adapted from Global Initiative for Chronic Obstructive Lung Disease; (GOLD)

29 Management Strategies Need to Address the Disease at Multiple Levels Agusti A, Vestbo J. AJRCCM 2011;184:

30 Management Need to Address Multiple Disease Components and Individualize Management Approach. Gibson PG et al. The Lancet 2010; 376:

31 Pharmacological Management of COPD Guideline-recommended COPD 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

32 Woodruff PG, et al. Lancet 2015; 385: Benefit risk Balance Should be Tailored to Individual Patient Characteristics Individual presentation and underlying mechanisms Mortality Disease progression Lung function Symptoms: cough, sputum production, and dyspnea Exercise tolerance Exacerbations Disability Health status and quality of life Individualization of treatment choices in COPD Present COPD pharmacological treatments Individual risk factors and comorbidities Pneumonia Tuberculosis Skin bruising Osteoporosis or fractures Muscle dysfunction Nutritional impairment Cataract Diabetes Tremor Cardiovascular events Neuropsychological events Gastrointestinal symptoms Expected benefits LABA; LAMA; LABA + LAMA; LABA + ICS; LABA + LAMA + ICS; LABA + roflumilast; LAMA + roflumilast Expected risks

33 Current Therapeutic Options for COPD Bronchodilators Beta 2 -agonists Short-acting beta 2 -agonists (SABA) Long-acting beta 2 -agonists (LABA) Anticholinergics Short-acting anticholinergics SAMA) Long-acting anticholinergics (LAMA) Methylxanthines Anti-inflammatory agents Corticosteroids Inhaled corticosteroids (ICS) Systemic corticosteroids Phosphodiesterase-4 inhibitors Combinations in one inhaler SABA / SAMA LABA / LAMA LABA / ICS ICS/LABA/LAMA Anti-oxidant agents N-acetylcysteine Mucolytics Carbocysteine N-acetylcysteine

34 2017 COPD Management

35 GOLD 2017 PHARMACOLOGIC TREATMENT ALGORITHM From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available at:

36 Other Pharmacologic Treatments

37 Inhaler Devices Pressurized Metered Dose Inhalers Dry Powder Inhalers Slow Mist Inhalers Jet Nebulizers High- Efficiency Vibrating Mesh Nebulizer Sims MW. Chest. 2011;140:

38 Issues of Inhaler Devices No single inhaler will satisfy the needs of all patients 28-68% of patients do not use inhalers correctly A sub-optimal technique can result in decreased lung delivery and potentially reduced efficacy 3 The proliferation of inhalation devices in the market can result in confusion for clinicians, nurses, respiratory therapists and patients 1 Each available device require specific inhalation techniques 1 Studies have demonstrated lack of knowledge in the use of devices by healthcare professionals % of HCPs are unable to adequately perform or describe inhalation techniques 4 Physicians need to select the right inhaler for each patient knowing each product s characteristics is key 4 1. Anna Murphy, SIMPLE Baverstock et al. Thorax, 2010;65:A117-A Labiris et al. Br J Clin Pharmacol, 2003;56, Lewis RM, Fink JB. Resp Crit Care Clin North Am 2001;7:

39 Emerging Therapies in COPD Management Novel therapies Novel formulations of existing medications Drugs used in treatment of comorbidities that may be useful in COPD Novel targets for pharmacologic therapy

40 Novel Formulations of Existing Medications Novel Bronchodilators Ultra LABAs Ultra LAMAs LABA/LAMA combinations LABA/ICS combinations Nebulized bronchodilators and combination therapies MABAs LABA: long acting beta-2 agonists; LAMA: long acting muscarinic antagonist; ICS; inhaled corticosteroid; MABA: bifunctional muscarinic beta-2 agonist Cazzola M, et al. Pharmacol Rev. 2012;64:

41 Drugs Used in Treatment of Comorbidities That May Be Useful in COPD Statins ACE Inhibitors Beta-blockers Peroxisome proliferator-activated receptor (PPAR) agonists Macrolides Mucolytic and Antioxidant Agents

42 Proportion of Participants Free from Acute Exacerbations of COPD N = 558 azithromycin N = 559 placebo Albert RK et al. N Engl J Med 2011;365:

43 Simvastatin for the Prevention of Exacerbations COPD Criner GJ et al. N Engl J Med 2014;370:

44 The Effect of N-acetylcysteine on COPD Exacerbations Jin-Ping Zheng J-P et al. Lancet Respir Med 2014; 2:

45 Smoking Cessation Nicotine antagonists Vaccination Antioxidants Inflammosome Inhibitors Reversal of Steroid Resistance Chemokine Antagonists Antibiotics Phagocytosis Anti proteases: Neutrophil elastase MMP9 inhibitors PDE inhibitors Epigenetic modulators Mediator Antagonists (TNF, IL-17, IL5, IL-13 antibodies) Kinase inhibitors Antifibrotic: Targeting TGFβ PPR agonists Regeneration: Stem Cell Retinoic Acid Mucoregulators: EGFR inhibitors Barnes PJ. Nature Rev Drug Discovery 2013; 12:

46 Non-pharmacological Options for COPD Patient Group A Low risk, fewer symptoms B Low risk, more symptoms C High risk, fewer symptoms D High risk, more symptoms Description <1 Exacerbation mmrc 0-1 or CAT <10 <1 Exacerbation mmrc >2 or CAT >10 >2 Exacerbations mmrc 0-1 or CAT <10 >2 Exacerbations mmrc >2 or CAT >10 Essential Smoking cessation for all patients who smoke The key intervention for smokers Can include pharmacologic treatment Pulmonary rehabilitation Recommended Depending on local guidelines Physical activity Influenza vaccination Pneumococcal vaccination Adapted from Global Initiative for Chronic Obstructive Lung Disease; (GOLD)

47 Defining Pulmonary Rehabilitation: Official ATS/ERS Statement Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the longterm adherence to health-enhancing behaviors. ATS = American Thoracic Society; ERS = European Respiratory Society Spruit MA, et al. Am J Respir Crit Care Med. 2013;188(8):e13-64.

48 Components of Pulmonary Rehabilitation Programs Pulmonary Rehabilitation Programs Exercise Training Involves the measurement of a number of physiologic variables, including maximum oxygen consumption, maximum heart rate, and maximum work performed Nutrition Counseling Important determinant of symptoms, disability, and prognosis in COPD; a reduction in BMI is an independent risk factor for mortality in patients with COPD Education Specific contributions of education to the improvements seen after pulmonary rehabilitation remain unclear Assessment and Follow-up 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 Accessed April 9, 2010.

49 Outcomes of Pulmonary Rehab in COPD 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 1 British Thoracic Society. Thorax. 2001; 56: American Thoracic Society. Am J Respir Crit Care Med. 1999;159: Guell R, et al. Chest. 2000;117: Saey D, et al. Am J Respir Crit Care Med. 2003;168: Casaburi R. Am J Respir Crit Care Med. 2003;168: Casaburi R, et al. Am J Respir Crit Care Med. 1997;155: Griffiths TL, et al. Lancet. 2000;355: Cote CG, et al. Am J Respir Crit Care Med. 2003;167:A38.

50 Monitoring and Follow-up In order to adjust therapy appropriately as the disease progresses, each follow-up visit should include a discussion of the current therapeutic regimen. Monitoring should focus on: Dosages of prescribed medications. Adherence to the regimen. Inhaler technique. Effectiveness of the current regime. Side effects. Treatment modifications should be recommended Global Initiative for Chronic Obstructive Lung Disease

51 Strategies to Ensure Adherence

52 Patient Education: Key Educational Messages for COPD Basic facts about COPD Contrast normal and COPD airways Roles of medications and potential adverse events Long-term maintenance and quick-relief medications Relevant environmental triggers and reducing exposures Building an action plan: when and how to take rescue actions Skills Inhalers, nebulizers, spacers, symptoms, and early warning signs

53 Non-Pharmacologic Treatment - Summary

54 Oxygen Therapy Introduced by Joseph Priestly (English scientist and clergyman) in 1774 Alvan Barach pioneered the use of oxygen therapy in COPD. 1 First systematic studies on the physiologic and clinical benefit of LTOT were reported in 1967 (Denver). 2 Long-term benefit confirmed in hypoxemic patients the MRC and NOTT. 3,4 LOTT study: No effect of oxygen therapy in patients with moderate or exercise-induced hypoxemia 1. Barach AL. JAMA 1922; 79: Levine BE et al. Ann Intern Med 1967;66: Report of the Medical Research Council Working Party. Lancet ; 1 ( 8222 ): Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980; 93( 3):

55 Oxygen therapy/ NIV Long-term oxygen therapy is indicated for stable patients who have: PaO 2 at or below 55 mmhg or SaO 2 at or below 88%, with or without hypercapnia confirmed twice over a three week period; or PaO 2 between 55 mmhg and 60 mmhg, or SaO 2 of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive cardiac failure, or polycythemia (hematocrit > 55%).

56 National Emphysema Treatment Trial Proc Am Thorac Soc May 1; 5(4): N Engl J Med 2003;348:

57 Tissue compression Flow regulation Bronchoscopic Approaches to LVR Zephyr- Endobronchial Valves (EBV) One-way valve leads to atelectasis. PulmonX Intrabronchial Valves (IBV) One-way valve leads to atelectasis. Spiration RePneu - Lung volume reduction coil (LVRC) PneumRx AeriSeal - Polymeric Lung Sealant Aeris InterVapor - Bronchoscopic Thermal Vapor Ablation (BTVA) Uptake Coil reduces lung volume by coiling and compressing disease tissue. Tissue sealant flows into alveolar compartment, polymerizes and seals target area. Heated water vapor produces thermal reaction with localized inflammation followed by fibrosis.

58 Interventional Therapy in Stable COPD

59 COPD: The Past, the Present and the Future Significant advancement in our knowledge over the last 300 years COPD is a heterogenous disease: Multiple inflammatory pathways involved Clinical and radiologic phenotypes are already identifiable. Pathobiological phenotypes /endotypes will emerge. Assessment of COPD should address symptoms, risk of exacerbations, comorbidities in addition to lung function Unmet needs with existing interventions Multiple novel targets of therapy are being evaluated and may be available in the future