Management of COPD: Lost Opportunities? Kamyar Afshar, DO Assistant Professor of Clinical Medicine Director, USC Center for Advanced Lung Disease

Objectives Background Information on COPD Surrogates of mortality in COPD Current management strategies How effective are we? Barriers to effective COPD care Proposed Model

Definition of COPD Chronic obstructive pulmonary disease (COPD) is a disease state characterized by persistent blockage of airflow from the lungs The airflow limitation is usually progressive Underwhelming definition?

Risk Factors for COPD Main risk factor

Defense cells are normally present in the lungs Defense cells are normally present in the lungs. When stimulated they increase in number and release protease (enzyme that breaks down lung tissue) unless counteracted by antiproteases (eg. Alpha 1-antitrypsin)

Domino Effect of Smoking Airway inflammation recruits higher levels of the defense cells (neutrophils and macrophages) in the lungs; they in turn increase in the number and release of proteases Tobacco use enhances the release of the protease enzyme as well as enhancing its activity Tobacco also inhibits the a1AT function (decreased protective enzymes) All this can lead to………..

Severe COPD/Emphysema

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 Coronary Heart Disease Stroke Other CVD COPD All Other Causes 2.5 2.0 1.5 1.0 0.5 –59% –64% –35% +163% –7% 1965 - 1998

COPD Mortality by Gender, U.S., 1980-2000 Number Deaths x 1000

Surrogates of COPD Mortality

Lung function over time Rate of 35 mL/year Modified version of Fletcher and Peto’s graph Br Med J 1977;1:1645 * Tobacco destroys a1AT function

Trajectory of a Patients with COPD Which part is more important Trajectory of a Patients with COPD Which part is more important? Or other? Symptoms Exacerbations Deterioration End of Life : FEV1, 6 min walk test; BODE index Time

Classification of COPD Severity by Spirometry FEV1 % pred Mild Stage I 80 Moderate Stage II 50–80 Severe Stage III 30–50 Very severe Stage IV <30 FEV1, Surrogate of Mortality? Mannino DM. GOLD Classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med 2006;100:115-122

Surrogates of Mortality 6-min walk Are there strategies to improve the distance thereby decreasing mortality? Pinto-Plata VM. The 6-min walk distatne: change over time and value as a predictor Of survival in severe COPD. Eur Respir J 2004;23:28-33

Management of COPD Grading Shortness of Breath to Detect Exacerbations Grade Degree of breathlessness related to activity 1 Not troubled by breathlessness except on strenuous exercise 2 SOB when hurrying or walking up a slight hill 3 Walks slower than contemporaries on level ground because of breathlessness, or has to stop for breath when walking at own pace 4 Stops for breath after walking about 100 m or after a few minutes on level ground 5 Too breathless to leave the house, or breathless when dressing or undressing Modified MRC

Surrogates of Mortality Dyspnea Nishimura K. Dyspnea is a better predictor of 5-year survival than airway obstruction In patients with COPD. Chest 2002;121: 1434-1440

Celli B. The body-mass index, airflow obstruction, dyspnea and exercise capacity in chronic obstructive pulmonary disease. N Engl J Med 2004;350:1005-1012

Trajectory of a Patients with COPD Which part is more important Trajectory of a Patients with COPD Which part is more important? Or other? Symptoms Exacerbations Deterioration End of Life : FEV1, 6 min walk test; BODE index Time

Classification of COPD Severity by Spirometry FEV1 % pred Mild Stage I 80 Moderate Stage II 50–80 Severe Stage III 30–50 Very severe Stage IV <30 Hurst JR, et al. Susceptibility to exacerbation in COPD. N Engl J Med 2010;363:1128-1138

Seemungal TAR. Time course and recovery of exacerbations in patients with Chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1608-1613

COPD Exacerbation Definition An acute change in a patient’s baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in therapy Causes of exacerbation can be both infectious and non-infectious Suissa S ,et al. Long-term natural history of COPD: Severe exacerbations and mortality. Thorax 2012;67:957-963

Worse Prognosis in Frequent Exacerbators ≥3 acute exacerbations requiring hospitalisation is associated with a risk of death 4.30 times greater than for those patients not requiring hospitalization Time (months) 10 20 30 40 50 60 0.2 0.4 0.6 0.8 1.0 Probability of surviving p<0.0001 A B C p=0.069 p<0.0002 Group A Patients with no acute exacerbations Group B Patients with 1–2 acute exacerbations of COPD requiring hospital management Group C Patients with ≥3 acute exacerbations of COPD requiring hospital management Key message: Patients with more exacerbations have a higher risk of mortality Soler-Cataluña et al. Thorax 2005; 60:925-931

Current COPD Management Strategies

While incurable, proper management of COPD can: COPD Management Goals While incurable, proper management of COPD can: Improve quality of life Improve exercise (functional) capacity Reduce exacerbation rates and prevent progression of disease Prevent and treat complications Reduce mortality It will not improve lung functions

Therapy based of stage of COPD IV: Very Severe FEV1/FVC < 70% FEV1 < 30% predicted or FEV1 < 50% predicted plus chronic respiratory failure III: Severe FEV1/FVC < 70% 30% < FEV1 < 50% predicted II: Moderate FEV1/FVC < 70% 50% < FEV1 < 80% predicted I. Mild FEV1/FVC < 70% FEV1 > 80% predicted Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long term oxygen if chronic respiratory failure. Consider surgical treatments

Combined Assessment of COPD Prediction for Exacerbations Patient is now in one of four categories: A: Less symptoms, low risk B: More symptoms, low risk C: Less symptoms, high risk D: More symptoms, high risk 4 (C) (D) > 2 3 (Exacerbation history) Risk (GOLD Classification of Airflow Limitation) Risk 2 (A) (B) <2 1 mMRC 0-1 CAT < 10 mMRC > 2 CAT > 10 Symptoms GOLD 2011

Manage Stable COPD: Pharmacologic Therapy Groups A, B, C or D severity assessment based on: FEV1: GOLD 1, 2, 3 and 4 Symptoms (mMRC or CAT questionnaires) score Exacerbations/year (C) (D)  LABA/ICS or LAMA   LABA/ICS or LAMA LABA + LAMA LABA/ICS + LAMA; LABA/ICS + PDE4; LAMA + PDE4  SABA or SAMA p.r.n.  LAMA or LABA SABA + SAMA; LABA or LAMA LABA + LAMA  (A) (B) GOLD 1 GOLD 2 GOLD 3 GOLD 4 Exacerbations per year ≥2 <2 Reference: Revised GOLD 2011 http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html mMRC 2+ CAT 10+ mMRC 01 CAT <10 GOLD 2011

Phenotypic Variance All patients COPD should be treated distinctly because there is a phenotypic variance (behave differently): COPD/Emphysema COPD/Chronic Bronchitis COPD/Asthma Exacerbator phenotype Alpha 1-antitrypsin deficiency

Co-Morbidities for COPD DivoM. Comorbidity and risk of mortality in patients with COPD. Am J Respir Crit Care 2012;186:155-161

Co-Morbidities for COPD Diagnosis Men (%) Women (%) Myocardial Infarction 27 14 Congestive Heart Failure 3 7 HTN 57 53 Dyslipidemia 49 54 GERD 60 68 Sinus issues 51 65 Anxiety/Depression 44 Osteoporosis 12 39 Cancer 4 6 Diabetes 26 25 Stroke 11 16 Known barrier to successful smoking cessation & adherence DivoM. Comorbidity and risk of mortality in patients with COPD. Am J Respir Crit Care 2012;186:155-161

Is this related to tobacco + alcohol? Or something else? Cirrhosis Emphysema CXR Is this related to tobacco + alcohol? Or something else?

Approximately 3% of COPD patients have alpha 1-antitrypsin deficiency Cirrhosis Emphysema CXR Approximately 3% of COPD patients have alpha 1-antitrypsin deficiency

Prevalence 3.4 million individuals with mutant AAT allele combinations worldwide1 PiZZ = 173,430 PiSZ = 1,011,069 PiSS = 2,260,801 Based on direct population screening studies, prevalence of PiZZ in the US may be 70,000 Only approximately 5,000 individuals in the US are currently diagnosed with PiZZ 95% undiagnosed Stoller JK. A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2012;185:246-259

Alpha1 - Antitrypsin Deficiency Phenotype Serum levels microMolar Mg/dL Risk of Lung Damage Risk of Liver Damage PiMM 20-53 130-200 PiMS 18-52 100-130 PiSS 20-48 130-300 PiMZ 15-42 80-100 Possibly Increased PiSZ 10-23 40-80 Increased PiZZ 3-7 15-50 Very High High PiNull Very high None PiMZ: rarely have serum levels below protective threshold PiSZ: 10% will have levels below protective threshold PiZZ: below the protective threshold

Range of serum levels Adapted from The Alpha-1 Foundation slide set. www.alphaone.org. Courtesy of H. Ari Jaffe, MD Bottom normal level Protective threshold When you check the levels in the blood, they may not always be reliable values Acute phase reactants Value can be increased 4-fold in an inflammatory state

PiMZ and PiMM When comparing PiMZ and PiMM, the degree of obstruction was more in the PiMZ group Even in low smoking history, PiMZ individuals had more severe emphysema on the CT scan Sorheim IC. A1-antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts. Chest 2010; 138:1125-1132

Smoking, Lung Function and a1AT 33 PiZZ patients with emphysema Age of onset of SOB Avg FEV1 value Rate of FEV1 decline Age of Death Smokers 32 years 38% 316 mL/yr 48 years Non-smokers 51 years 77% 80 mL/yr 67 years normal FEV1 declines 25-30 mL/ yr after age 35 Janus ED. Smoking, lung function and alpha1 antitrypsin deficiency. Lancet 1985;152-154

Actively address the Co-morbidity issues Augmentation therapy for qualified patients w/ Alpha 1-antitrypsin deficiency Actively address the Co-morbidity issues Smoking cessation, immunizations Pulmonary Rehabilitation Miravitles M, et al. A new approach to grading and treating COPD based on clinical phenotypes: summary of the Spanish COPD guidelines. Prim Care Respir Med J 2013;22:117-121

Recommendations vs. Current Practice De Oliviera JCM. Clinical significance in COPD patients followed In real practice. Multidisiplinary Respiratory Medicine 2013;8:43

Utilization of post exacerbation pulmonary rehab over 3 months Pulmonary Rehab improves functional capacity as well as exacerbation rates Usual Care Pulm Rehab OR (95% CI) Pulm Rehab vs usual care P value Total participants 30 patients Hospital admission for 2nd exacerbation 10 (33%) 2 (7%) 0.15 (0.03 – 0.72) 0.02 Hospital or ED attendance for 2nd exacerbation 17 (57%) 8 (27%) 0.28 (0.10 – 0.82) 1. Seymour JM. Outpatient pulmonary rehabilitation following acute exacerbations of COPD. Thorax 2010;65:423-428 2. Puhan MA. Pulmonary rehabilitation following exacerbations for chronic obstructive pulmonary disease.Cochrane Database Syst Rev 2011;10:CD005305

Participate rates in pulmonary rehab Once enrolled, there is a low drop out from 9.7% 34-49% of participants attend after being referred to pulmonary rehab Why the discrepancy? 1. Spruit MA. What to do before pulmonary rehabilitation to improve adherence? Chron Respir Dis 2010;7:131-133 2. Harris D. Improving he uptake of pulmonary rehabilitation in patients with COPD. Br J Gen Pract 2008;58:703-710 3. Sohanpal R. Reporting participation rates in studies of non-pharmacological interventions for patients with chronic obstructive pulmonary disease: a systematic review. Systematic Reviews 2012;1:66

Barriers to “referral” to PR Perceived costs Perceived to only be for end-stage category Reserved for those with impaired functional status; physical challenges Patient motivation Transportation issues Time

Barriers to Effective COPD Management - Access - Physician Knowledge - Patient Adherence

Principles of Value-Based Care “Patients will have access to healthcare providers and quality of care will be improved, thereby cutting the costs” Implementing known best practices Better diagnosis means that the right condition is treated, improving outcomes and avoiding ineffective treatments

“Increased Access to Care” Access (Merriam-Webster dictionary) A way of getting near, at, or to something or someone Freedom or ability to obtain or make use of something An increase by addition < a sudden access of wealth>

“Increased Access to Care” A way of getting near, at, or to office clinic or healthcare provider or tools for proper assessment Freedom or ability to obtain or make use of educational opportunities An increase by addition < a sudden access of health; time spent with the provider>

Health Care Professional Responsibilities Ensuring an accurate diagnosis Determining appropriate phenotype, testing for alpha 1-antitrypsin deficiency Appropriate monitoring Spirometry, Dyspnea scoring system, 6 min walk Recognizing exacerbation events Prescribing appropriate treatment Assessing the effectiveness/adherence Access to the medications (eg. 30 day vs. 90 day supply, financial restrictions, social stigma, etc)

Primary Care Setting Surveyed 3,265 patients worldwide1 68% of COPD patients are seen in primary care setting1 32% of COPD patients with pulmonary specialists1 In Family Medicine clinics, 58% (4.6 hours/day) of all visits are for acute problems and their follow up care2 “acute care takes precedence over both prevention and chronic disease management” Halpern MT. The burden of COPD in the USA. Results from Confronting COPD survey. Resp Med 2003;97:S81-S89 Ostbye T. Is there time for management of patients with Chronic disease in primary care? Ann Fam Med 2005;3:209-214

Percentage of patients reporting > 1 class of prescribed medication Patients reporting at least 1 lab test for COPD during the 12 months prior to the survey Halpern MT. The burden of COPD in the USA. Results from Confronting COPD survey. Resp Med 2003;97:S81-S89

Barriers to COPD care delivery Lack of office logistics Spirometry Knowledge of guideline recommendations Proper recognition of COPD and co-morbidities Time constraints. The recommended minimum time to provide high quality medical management for COPD is………..

Duke University Ostbye T. Is there time for management of patients with Chronic disease in primary care? Ann Fam Med 2005;3:209-214

Influences of COPD Adherence Bourbeau J. Patient adherence in COPD. Thorax 2008;63:831-838

Trialed Protocol Primary Care: specific clinics with access to spirometry, pulse oximetry, nebulizers and oxygen Include a trained specialist nurse Smoking cessation program Patient education

Measures at exacerbation visit 1 Multicenter analysis: 22 month follow up = 458 Sundh J. Management of COPD exacerbations in primary care: a clinical cohort study. Prim Care Respir J 2013;22: online ahead print

Planned follow-up and time to a second exacerbation 238 pts had a 2nd exacerbation Extra planned visit to nurse Extra planned visit or telephone call by doctor No extra scheduled visit Sundh J. Management of COPD exacerbations in primary care: a clinical cohort study. Prim Care Respir J 2013;22: online ahead print

In Closing…. A proactive and integrated approach with each discipline utilizing their strengths can improve the quality of life for individuals with COPD Preventative Care Immunizations Social Support Network Caregivers Support Group Meetings Individualized Treatment Plans Based on phenotypes and exacerbation history Home spirometry Address Co-morbidities Depression, axiety Pulmonary hypertension Cardiac disorders Physician Primary care Specialist Nurse Coordinator Physical , Respiratory & Occupational Therapist Pharmacist Medical Social Worker Registered Dietician Psychologist Psychiatry

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