COPD and Severe Asthma Update Updates in Internal Medicine March 8 th , 2019 Douglas Beach, MD, MPH BIDMC Pulmonary, Critical Care, and Sleep Medicine Beth Israel Deaconess Medical Center
Overview • Identification and management of COPD • How to think about “Asthma/COPD” overlap • New monoclonal antibodies in treating severe asthma (and COPD?) Beth Israel Deaconess Medical Center
Outpatient Case • 66 year old man comes to clinic for shortness of breath • Diagnosed with “asthma” 8 -10 years ago • Former smoker, 20 pk year, quit 30 years ago • Has been on 2 courses of prednisone and antibiotics for exacerbations in the past 3 months • No PFTs are available, yet… Beth Israel Deaconess Medical Center
Global initiative for chronic Obstructive Lung Disease (GOLD) • 1998: Created by the U.S. NHLBI and WHO • Goal of increasing awareness of COPD to improve prevention and management • Updated recommendations 2018 • www.goldcopd.org Beth Israel Deaconess Medical Center
Definition of COPD (GOLD report 2009) Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease… Characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. Beth Israel Deaconess Medical Center
Burden of COPD • 10% of general population and 50% of heavy smokers • Excess health expenditures: $6,000 per year/patient (6% of total healthcare expenditures U.S.) • COPD is the 4th leading cause of death • The number of deaths from COPD is increasing in women. • History of asthma increases risk of developing COPD 12- fold • 20% of patients with asthma will develop irreversible airway obstruction Beth Israel Deaconess Medical Center
Consider COPD Diagnosis if patients: – Symptoms • Dyspnea • Chronic cough • Chronic sputum production – Have a history of exposure to risk factors (smoking/tobacco, biomass cooking, occupational and environmental exposures to dusts, chemicals, pollution) Beth Israel Deaconess Medical Center
The “ GOLD ” Standard “ Spirometry should be performed on individuals over age • 40 with symptoms or history suggestive of COPD ” • Remember, it is a preventable and treatable disease! Beth Israel Deaconess Medical Center
Spirometry is necessary for diagnosis Beth Israel Deaconess Medical Center
GOLD 2018: Assessment of symptoms/risk of exacerbations (Group A, B, C, D) mMRC score ≥ 2 mMRC score 0-1 CAT ≥ 10 CAT < 10 ≥ 2 C D exacerbations or ≥ 1 hospital admission 0 or 1 A B exacerbations and no hospitalization Beth Israel Deaconess Medical Center
Back to our patient • 66 year old with “asthma”, former smoker • FEV1/FVC ratio 0.54 (73% predicted) • FEV1 58% predicted (moderately severe) • Two exacerbations not requiring hospitalization • mMRC score 1 • CAT: Less than 10 GOLD Grade 2, Group C !! Beth Israel Deaconess Medical Center
www.goldcopd.org Beth Israel Deaconess Medical Center
Recommended initiation treatment of COPD by GOLD Group Group A: – Short acting bronchodilator when needed Group B: - One or more long-acting bronchodilators (LABA /LAMA) Group C: – LAMA – LABA/LAMA or LABA plus Inhaled corticosteroids if repeated exacerbations occur Group D: - LABA/LAMA/ICS (“triple therapy”) – Consider macrolide therapy for non-smokers – Consider Roflumilast (Daliresp) if FEV1 less than 50% and recurrent exacerbations Beth Israel Deaconess Medical Center
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COPD Therapy Goals – Symptom control (dyspnea, exercise limitation, cough, wheezing) – Reduce exacerbation frequency – Reduce need for hospitalizations – Reduce mortality Beth Israel Deaconess Medical Center
Reducing Mortality • Smoking cessation should be first and foremost focus of treatment as it is the only proven method of reducing mortality and rate of lung function decline • Oxygen therapy for patients with resting hypoxemia has been shown to reduce mortality – ≤ 88 % (PaO2 55 mmHg) oxygen should be prescribed for 15 -18 hours a day to keep PaO2 > 60mmHg and SaO2 > 90%** – ≤ 89% with presence of cor pulmonale 1. **Niewoehner DE. NEJM 2010;362:1407-16. 2. NOTT. Ann Intern Med 1980;93:391-8. 3. MRCWP. Lancet 1981;1:681-6. Beth Israel Deaconess Medical Center
Smoking Cessation 5 Step Program US Public Health Service 1. ASK 2. ADVISE 3. ASSESS 4. ASSIST 5. ARRANGE JAMA 2000; 28:3244-54 NEJM 2011;365:1222-31 Beth Israel Deaconess Medical Center
Smoking Cessation Fiore M, et al. NEJM 2011 • For patients who are not ready to quit… Motivational Interviewing to discuss the “ 5 R ’ s ” • – personally relevant reasons to quit – risks associated with continued smoking – rewards for quitting – roadblocks to successful quitting – repetition of the counseling at subsequent clinic visits Beth Israel Deaconess Medical Center
Acute Exacerbations of COPD • Typically defined by 2 or more cardinal features: – Change in baseline shortness of breath – Change in sputum volume – Change in sputum purulence Exacerbations are “ a natural event in the course of the disease… ” treated with systemic steroids, antibiotics, and bronchodilators. Beth Israel Deaconess Medical Center
AECOPD (Hurst JR, et al, 2010) • Rates of exacerbation increase with: – decrease in FEV1 (and GOLD stage) – prior history of exacerbations – GERD – Elevated WBC (new data also note eosinophilia associated with exacerbations) GOLD stage Rate of AE per % with 2+ AE/year year (per person) 2 0.85 22% 3 1.34 33% 4 2.0 47% Beth Israel Deaconess Medical Center
Azithromycin for Prevention of AECOPD (NEJM 2011;365:689-98.) • 1142 patients, RCT of azithromycin 250 mg/day vs. placebo • 1 year f/u ~90% both groups • Frequency of exacerbations lower in azithromycin group Group Rate of AECOPD P per patient-year Azithromycin 1.48 0.01 Placebo 1.83 Beth Israel Deaconess Medical Center
Advanced therapies for Severe COPD – Nutrition Therapy – Surgical Options: endoscopic lung volume reduction, Lung Volume Reduction Surgery, Lung Transplant Evaluation. – Referral to pulmonary medicine or other specialist: • Persistent symptoms and exacerbations. • Consider alternative diagnosis: severe asthma, bronchiectasis, alpha-1 antitrypsin deficiency. • Significant comorbidities: cardiac, sleep disorders, or immune deficiency. • Discussion of goals of care and palliation of symptoms. Beth Israel Deaconess Medical Center
Outpatient Case • 66 year old man comes to clinic for shortness of breath • Diagnosed with “asthma” 8 -10 years ago • Former smoker, 20 pk year, quit 30 years ago • Has been on 2 courses of prednisone and antibiotics for exacerbations in the past 3 months • Does he have ACOS? Beth Israel Deaconess Medical Center
ACOS (Asthma/COPD Overlap Syndrome) • COPD: Caused primarily by smoking, pollution, occupational exposures. Occurs after age 40-45 – Inflammation caused by neutrophilic inflammation and CD8 lymphocytes • ASTHMA: • Primarily eosinophilic inflammation driven by TH2 lymphocytes • typically in childhood with allergies. However, asthma develops in adulthood in a sub-group of patients • Typically associated with bronchial hyper- responsiveness Beth Israel Deaconess Medical Center
ACOS (Asthma/COPD Overlap Syndrome) • Think about ASTHMA • Triggers? • Allergies? Allergy testing? IgE? • PFTs normalize (or near normal)? • Remember: Severe, persistent asthma that is UNCONTROLLED looks like COPD • Patients with ASTHMA component – Trigger avoidance, Trigger avoidance, Trigger avoidance – Leukotriene modifier – LAMA add on therapy – Immunotherapy? Beth Israel Deaconess Medical Center
Principles of treatment ACOS • Patient Education • Trigger avoidance! – Vaccination – Irritants (allergens, irritants, smoking) – GERD • “Rescue” inhalers • Controller medications • Compliance/Adherence • Monitoring/follow up Beth Israel Deaconess Medical Center
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Biologic Therapies for Asthma • Omalizumab: Anti-IgE Mab (FDA 2003) • Mepolizumab: Anti-IL5 Mab (FDA 2015) • Reslizumab: Anti-IL5 Mab (FDA 2016) • Benralizumab: Anti-IL5R Mab (FDA 2017) • Dupilumab: Anti-IL4/IL13 Mab (FDA 2018) Beth Israel Deaconess Medical Center
Omazilumab • FDA approved 2003 • 200,000 patients treated from 2003-2016 • Moderate to severe persistent allergic asthma on high dose ICS • Positive skin/specific IgE tests with IgE 30 to 700 IU/mL • Binds IgE to prevent activation of mast cells and basophils which leads to further release of inflammatory mediators (histamine, leukotrienes, tryptase, inflammatory cytokines) Beth Israel Deaconess Medical Center
Omalizumab • Hanania NA, et al. Ann Int Medicine. 2011 • 850 pts severe asthma on ICS and LABA, IgE 30-700 IU/mL, weight 30kg-150kg • “poorly controlled asthma” • 25% reduction in exacerbations Beth Israel Deaconess Medical Center
Targeting Eosinophilic Asthma/COPD TH2-High Targets: Eosinophil Targets: IL-5 IL-4 IL-13 Surface Targets (i.e. Siglec-8, EMR-1) Adapted from: Wills-Karp and Karp, Science , 2004 Beth Israel Deaconess Medical Center
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