AECOPD: Management and Prevention

AECOPD: Management and Prevention Neil MacIntyre MD Duke University Medical Center Durham NC AECOPD: Management and Prevention AECOPD: Definitions and impact Acute management of AECOPD Preventing AECOPD. Barnes PJ. N Engl J Med. 2000;343:269-80. Professor P.J. Barnes, MD, National Heart and Lung Institute, London UK Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK 1

Proportion of 1965 Rate Consequences Of COPD Exacerbations Negative impact on quality of life Impact on symptoms and lung function Accelerated lung function decline EXACERBATIONS Increased economic costs Increased Mortality Duke data 2013: 270 AECOPD admissions 20% readmit in 30 days Majority AECOPD but also CHF and combos COPD: Direct Cost COPD Projected to Be the Third-Leading Cause of Death by 2020 $20 $18 $16 $14 $12 Nursing Home Care* Home Health Care* Physician Services 3.0 2.5 2.0 Proportion of 1965-1998 Rate, Percentage Change in Age-Adjusted Death (US) $10 $8 $6 Hospital Care Prescription Drugs 1.5 1.0 $4 $2 $0 COPD Morbidity and Mortality: 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases. NIH/NHLBI. May 2002. 0.5 0.0-59% -64% -35% +163% -7% Coronary Heart Disease Stroke Other CVD COPD All Other Causes Global Initiative for Chronic Obstructive Lung Disease teaching slide kit. Available at: www.goldcopd.com/slides/download.ppt. 2

AECOPD: Management and Prevention AECOPD: Definitions and impact Acute management of AECOPD Preventing AECOPD AECOPD: Assessments R/O other problems Arterial blood gas measurements: PaO 2 < 60 mm Hg with or without PaCO 2 > 48 mm Hg on RA indicates respiratory failure. Chest radiographs: useful to exclude alternative diagnoses. ECG: may aid in the diagnosis of coexisting cardiac problems. Whole blood count: identify polycythemia, anemia or bleeding. Purulent sputum indication to begin empirical antibiotics Biochemical tests: detect electrolyte disturbances, diabetes, and poor nutrition. Spirometric tests: not recommended during an exacerbation. Contrasted CT: consider in pts at risk with severe hypoxemia Manage Exacerbations: Treatment Options AECOPD: Oral CS RCTs Treatment Failures Oxygen: titrate to improve the patient s hypoxemia with a target saturation of 88-92%. Bronchodilators: Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics are preferred. Systemic Corticosteroids: Shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay. A dose of 30-40 mg prednisolone per day for 10-14 days is recommended. Oxygen titrated to SpO2 Manage Exacerbations: Treatment Options Antibiotics should be given to patients with: Three cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence. Who require mechanical ventilation. SpO2 target 88-92 SpO2 target > 95 Should be humidified Chest 2004;125:1061 3

Meta-analysis of the Benefits of Antibiotics in AECOPD Elmes et al. 1957 Berry et al. 1960 Fear and Edwards. 1962 Elmes et al. 1965 Petersen et al. 1967 Pines et al. 1972 Nicotra et al. 1982 Anthonisen et al. 1987 Jorgensen et al. 1992 Overall Favors placebo Favors antibiotic 1.0 0.5 0 0.5 1.0 1.5 Effect size Saint S. JAMA. 1995;273:957-960. Acute Respiratory Failure in COPD Narrowed airways increases inspiratory work Narrowed airways increases air trapping and decreases muscle force generation capability Net result is hypercapneic respiratory failure Manage Exacerbations: Treatment Options Noninvasive ventilation (NIV) for patients hospitalized for acute exacerbations of COPD: Improves respiratory acidosis, decreases respiratory rate, severity of dyspnea, complications and length of hospital stay. Decreases mortality and needs for intubation. GOLD Revision 2011 NPPV in Acute Exacerbations of COPD: Risk of Treatment Failure (Mortality, Intubation, Intolerance) AECOPD: Management and Prevention AECOPD: Definitions and impact Acute management of AECOPD Preventing AECOPD Ram FS et al. Cochrane Database Syst Rev. 2003;1:CD004104. Reproduced with permission. Lightowler JV et al. BMJ. 2003;326:185-190. 4

SUBCLINICAL COPD CLINICAL COPD Percentage Correctly Diagnosed With Obstructive Lung Disease Risk (GOLD Classification of Airflow Limitation) Risk (Exacerbation history) Clinical COPD Is Just The Tip Of The Iceberg COPD Often Unrecognized During Hospitalization. 2 Million severe SUBCLINICAL COPD *Repeated exacerbations and hospitalizations Mannino. MMWR Surveill Summ. 2002;51(6):1-16. 10 Million Dx? Millions at risk 90 80 70 60 50 40 30 20 10 0 Mild Moderate Severe Very Severe Reproduced with permission. Zaas D et al. Chest. 2004;125:106-11. Admission Diagnosis Discharge Diagnosis Diagnosis of COPD COPD: the spirogram EXPOSURE TO RISK FACTORS AND/ OR SYMPTOMS sputum cough dyspnea wheezing Normal Obstructed SPIROMETRY Adapted with permission from the GOLD web site. Available at: www.goldcopd.com. Restricted GOLD Staging: FEV1/FVC < 0.7, then FEV1 % pred: Mild >80%, Mod 50-79%, Severe 30-49%, Very Severe <30% GOLD 2014: Combined Assessment of COPD Spirometry not enough misses emphysema, symptoms, exacerbation risk Three components determine severity of disease Spirometry to assess degree of airflow limitations Symptom assessment Risk of exacerbations Combined Assessment of COPD 4 3 2 1 (C) (A) (D) (B) > 2 1 0 CAT = COPD assessment test; mmrc = modified Medical Research Council. Global Initiative for Chronic Obstructive Lung Disease. 2014. http://www.goldcopd.org/guidelines-global-strategyfor-diagnosis-management.html. Accessed March 6, 2014. mmrc 0-1 CAT < 10 mmrc > 2 CAT > 10 Symptoms (mmrc or CAT score)) 5

Manage Stable COPD: Non-pharmacologic Prevention of COPD Exacerbations: Pneumococcal and Influenza Vaccinations Patient Group Essential Recommended Depending on local guidelines Pneumococcal vaccination COPD hospitalization All-cause mortality A Smoking cessation (can include pharmacologic treatment) Physical activity Flu vaccination Pneumococcal vaccination Pneumococcal + influenza vaccination COPD hospitalization B, C, D Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Flu vaccination Pneumococcal vaccination All-cause mortality 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2.0 Relative Risk (95% CI) Adapted from Nichol et al. Arch Intern Med. 1999;159:2437-2442 (A). COPD natural history depends on tobacco exposure/sensitivity Smoking Cessation First thing you have to do to get out of hole is stop digging Nicotine is incredibly addictive spontaneous quit rates <5%/year What can help? Nicotine replacement Welbutrin Varenicline Formal programs (ALA, ACS) Manage Stable COPD: Pharmacologic Therapy (Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.) Current Inhaled Medications for COPD Patient Recommended First choice Alternative choice Medication Brand Usual Starting Dose Duration β 2 -Agonists A B C SAMA prn or SABA prn LAMA or LABA ICS + LABA or LAMA LAMA or LABA or SABA and SAMA LAMA and LABA LAMA and LABA or LAMA and PDE4-inh. or LABA and PDE4-inh. Short-acting Albuterol ProAir, Proventil, Ventolin 2 puffs q 4-6 hrs PRN 4-6 h Levalbuterol Xopenex HFA 2 puffs q 4-6 hrs PRN 4-6 h Pirbuterol Maxair Autohaler 2 puffs q 4-6 hrs PRN 5 h Long-acting Formoterol Foradil Aerolizer, Perforomist, Brovana 1 inhaled capsule bid 12+ h Indacaterol Arcapta Neohaler 1 inhaled capsule daily 24+ h Salmeterol Serevent Diskus 1 puff bid 12+ h D ICS + LABA and/or LAMA ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and LABA or LAMA and PDE4-inh. HFA = hydrofluoroalkane. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fbe6d514-9d89-48f7-80a0-d1b41983f203. Accessed April 3, 2014. Cazzola M, et al. Drugs Today. 2011;106:84-90. http://www.pdr.net/. Accessed April 3, 2014. PL Detail- Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August 2013. 6

Current Inhaled Medications for COPD Cont d Medication Brand Usual Starting Dose Duration Anticholinergics Short-acting Ipratropium bromide Atrovent 2 puffs qid 6-8 h Long-acting Aclidinum Tudorza Pressair 1 puff bid 24+ h Tiotropium bromide Spiriva Handihaler 1 inhaled capsule daily 24+ h Combination Bronchodilators Albuterol/ipratropium Combivent 2 puffs q 4-6 hrs PRN 4-6 h Umeclidinum/Vilanterol Anoro Ellipta 1 puff daily 24 h Current Inhaled Medications for COPD Cont d Medication Brand Usual Starting Dose Duration Inhaled Corticosteroids Budesonide Pulmicort Flexhaler 1-2 puffs bid 12 h Fluticasone Flovent HFA 1-2 puffs bid 12 h Beclomethasone QVAR 1-2 puffs bid 12 h Combination Inhalers Formoterol/Budesonide Symbicort 2 puffs bid 12 h Fluticasone/Salmeterol Advair Diskus Advair HFA 1 puff bid 2 puffs bid Fluticasone/Vilanterol Breo Ellipta 1 puff daily 24 h 12 h * NEW: Titropium/olodaterol (Stiolto) http://www.pdr.net/. Accessed April 3, 2014. Salmon M, et al. J Pharmacol Exp Ther. 2013;345(2):260-70. Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1):218-30. PL Detail-Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August 2013. HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4. PL Detail-Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August 2013. http://www.pdr.net/. Accessed April 3, 2014. Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1):218-30. Current Oral Medications for COPD Medication Brand Usual Starting Dose Duration Corticosteroids Methylprednisolone Prednisolone Prednisone PDE4 Inhibitor 4-48mg/day depending on disease and response 5-60mg/day depending on disease and response 5-60mg/day depending on disease and response 12-24 h 12-24 h 12-24 h Roflumilast Daliresp One 500 mcg tablet daily 17+ h HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4. Using Oral Corticosteroids: a toolbox. Pharmacist s Letter/Prescriber s Letter. 2010;26(5):260507. http://www.pdr.net/. Accessed April 3, 2014. Preventing AECOPD Preventing AECOPD The phospodiesterase-4 inhibitor roflumilast may be useful to reduce exacerbations for patients with FEV 1 < 50% of predicted, chronic bronchitis, and frequent exacerbations. The phospodiesterase-4 inhibitor roflumilast may be useful to reduce exacerbations for patients with FEV 1 < 50% of predicted, chronic bronchitis, and frequent exacerbations. Also daily azithromycin? N-acetyl cycteine? 7

Pharmacotherapy Management (PCE) 2 rates are reported: 1. Patients dispensed a systemic corticosteroid within 14 days of event 2. Patients dispensed a bronchodilator within 30 days of event PCE Performance 2008 2012 90.0 Pharmacotherapy: Corticosteroids (HMO) PCE Performance 2008 2012 90.0 Pharmacotherapy: Bronchodilators (HMO) 85.0 80.0 75.0 Commercial Medicaid Medicare 85.0 80.0 75.0 Commercial Medicaid Medicare 70.0 70.0 65.0 65.0 60.0 60.0 55.0 55.0 50.0 50.0 2008 2009 2010 2011 2012 2008 2009 2010 2011 2012 Pulmonary rehabilitation Education chronic management acute management Exercise deconditioning common may need bronchodilators/o2 Psycho-social support 8

Hospitalizations, Puhan 2011 Cochrane Database Syst Rev. 2011 Oct 5;(10):CD005305. doi: 10.1002/14651858.CD005305.pub3. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Puhan MA1, Gimeno-Santos E, Scharplatz M, Troosters T, Walters EH, Steurer J. AUTHORS' CONCLUSIONS: Evidence from nine small studies of moderate methodological quality, suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients who have recently suffered an exacerbation of COPD. Can Patients Be Given an Action Plan to Self Manage AECOPD? Yes.But. Conflicting data from 2 large VA trials First showed remarkable reduction in need for hospitalizations etc if patients educated to start antibiotics promptly at symptom onset Second showed worse outcomes using a similar but less intensive strategy 9

Can Patients Be Given an Action Plan to Self Manage AECOPD? Yes.But. Conflicting data from 2 large VA trials First showed remarkable reduction in need for hospitalizations etc if patients educated to start antibiotics promptly at symptom onset Second showed worse outcomes using a similar but less intensive strategy Take home message: Self management offers advantage of prompt therapy but patients need to know when to call for help Barriers Clinician barriers Proper diagnosis/staging/prescribing per guidelines Patient barriers Understanding complex medication regimens Adherence to treatment plans (both pharmaceutical and non-pharmaceutical) System barriers Costs of medications Clinical support structures AECOPD: Management and Prevention AECOPD: Definitions and impact Acute management of AECOPD Preventing AECOPD 10