Disclosures. Learning Objectives

Transcription

1 Disclosures Dr. Corbridge's spouse is an employee of GlaxoSmithKline pharmaceutical company (effective May 1, 2018). This activity is supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. Learning Objectives Review evidence-based strategies for screening, diagnosis, and assessment of COPD. Describe the most current guideline recommendations for the pharmacologic treatment of COPD, including agents discussed in the guidelines. Describe the most current guideline recommendations for the nonpharmacologic treatment of COPD. Recognize acute exacerbations of COPD. Discuss strategies for promoting patient adherence to COPD therapy. 1

2 COPD Guidelines Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 Global Strategy for Prevention, Diagnosis, and Management of COPD 2018 GOLD Pocket Guide COPD Diagnosis and Management At-A-Glance Desk Reference Asthma, COPD, and Asthma-COPD Overlap Syndrome Spirometry Guide COPD A common, preventable, and treatable disease Characterized by persistent airflow limitation Typically progressive Associated with an enhanced chronic inflammatory response in the airways and lung due to noxious particles or gases Exacerbations and comorbidities contribute to the overall severity in individual patients COPD Common symptoms: Progressive dyspnea Cough Sputum production Symptoms are often underreported! Associated with significant comorbidities Increase morbidity and mortality May have periods of worsening baseline symptoms Important to prevent exacerbations 2

3 US Burden of COPD Age-adjusted death rates for the 10 leading causes of death in 2016: United States, 2015 and 2016 Prevalence of COPD among adults aged 18 years, 2014 Cause of Death Number* Heart disease Cancer Unintentional injuries 47.4 Chronic lower respiratory diseases 40.6 Stroke 37.3 Alzheimer s disease 30.3 Diabetes 21.0 Influenza and pneumonia 13.5 Kidney disease 13.1 Intentional Self Harm (Suicide) 13.5 *Deaths per 100,000 U.S. standard population Kochanek KD, et al. Mortality in the United States, NCHS Data Brief, no 293. Hyattsville, MD: National Center for Health Statistics (Data source: CDC Behavioral Risk Factor Surveillance System [BRFSS], 2014.) Global Burden of COPD Estimated global prevalence: 11.7% 3 million deaths annually The prevalence of COPD is expected to rise over the next 30 years due to: Increasing prevalence of smoking in developing countries Aging populations in high-income countries By 2030, a predicted 4.5 million COPD-related deaths will occur annually COPD imparts a significant economic burden COPD is Underrecognized and Underdiagnosed! 3

4 Risk Factors for COPD Tobacco smoke Greater exposure = greater risk Air pollution Indoor Biomass fuels/coal Outdoor Occupational dust and chemicals Genes Respiratory infections Asthma and airway hyperreactivity Socioeconomic status Gender Age Women develop COPD at a younger age Are less likely to be diagnosed with COPD than men when presenting with the same symptoms Are more likely to die from COPD than men COPD in Women American Lung Association. Photo: University of Illinois at Chicago. Used with permission. Pathology and Pathogenesis Noxious particle Susceptible host Lung inflammation structural changes Oxidative stress Inflammatory cells & mediators Inflammatory mediators Peribronchiolar and interstitial fibrosis 4

5 Pathology and Pathogenesis Airway limitation and gas trapping Gas exchange abnormalities Mucus hypersecretion Pulmonary hypertension Hogg JC. Lancet. 2004;364(9435): ; Used with permission. Diagnosis Diagnosing COPD Symptoms Breathlessness Cough Sputum Exposure to Risk Factors Tobacco Pollution Occupation Physical Exam & Spirometry Required to establish diagnosis 5

6 Physical Exam Airflow obstruction: Wheezing during auscultation Prolonged expiration Severe emphysema indicated by: Hyperinflation Low diaphragmatic position Decreased intensity of heart and breath sounds Severe disease suggested by: Pursed-lip breathing Use of accessory respiratory muscles Retraction of intercostal spaces Pulmonary hypertension No clubbing Assessment of COPD Determine impact on patient s health status COPD Assessment Test (CAT) Modified Medical Research Council (MMRC) dyspnea/breathlessness scale Clinical COPD Questionnaire (CCQ) Determine degree of airflow limitation Spirometry Assess risk of exacerbations, hospitalizations Past predicts future Increases with worsening airflow limitations Identify and treat comorbidities Modified MRC (mmrc) Dyspnea Scale Grade I only get breathless with strenuous exercise. 0 I get short of breath when hurrying on the level or walking up a slight hill. I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level. I stop for breath after walking about 100 yards or after a few minutes on the level. I am too breathless to leave the house. or I am breathless when dressing mmrc = Modified Medical Research Council Dyspnea Scale 6

7 COPD Assessment Test (CAT) I have no phlegm (mucus) in my chest at all My chest does not feel tight at all When I walk up a hill or one flight of stairs I am not breathless I am not limited doing any activities at home I am confident leaving my home despite my lung condition I sleep soundly I have lots of energy My chest is completely full of phlegm (mucus) My chest feels very tight When I walk up a hill or one flight of stairs I am very breathless I am very limited doing any activities at home I am not at all confident leaving my home despite my lung condition I don t sleep soundly because of my lung condition I have no energy at all Total Score: Diagnosis of COPD Spirometry is required to make the diagnosis of COPD. Photo: University of Illinois at Chicago. Used with permission. Spirometry FVC (forced vital capacity): Maximum volume of air that can be exhaled during a forced maneuver FEV 1 (forced expired volume in one second): Volume expired in the first second of maximal expiration after a maximal inspiration. This is a measure of how quickly the lungs can be emptied. FEV 1 /FVC: FEV 1 expressed as a percentage of the FVC, gives a clinically useful index of airflow limitation 7

8 Obstruction by Spirometry FEV 1 falls more than FVC FEV 1 /FVC < 0.70 Volume (L) FEV 1 / FVC =.73 Normal COPD FEV 1 / FVC =.26 FVC 1 TLC 0 FEV Time (sec) Graph created by Tom Corbridge. Used with permission. Hyperinflation in COPD Normal COPD Flow (L/sec) Volume (L) Graph created by Susan Corbridge. Used with permission. Hyperinflation in COPD Normal COPD Flow (L/sec) Volume (L) Graph created by Susan Corbridge. Used with permission. 8

9 Pulmonary Function Tests in COPD Post-bronchodilator FEV 1 /FVC 0.70 confirms irreversible obstruction Classically associated with increased lung volume and decreased diffusion capacity GOLD Spirometric Classification Based on Post-Bronchodilator FEV1 GOLD 1: Mild FEV1/FVC <.70 FEV1 80% predicted GOLD 2: Moderate FEV1/FVC <.70 50% FEV1 < 80% predicted GOLD 3: Severe FEV1/FVC <.70 30% FEV1 < 50% predicted GOLD 4: Very Severe FEV1/FVC <.70 FEV1 < 30% predicted GOLD ABCD Assessment Tool (Refined) Patient example: FEV1 47% predicted CAT score 18 = GOLD Grade 3, Group B No exacerbations 2018 Global Initiative for Chronic Obstructive Lung Disease, Inc. Used with permission. Do not reproduce in print. 9

10 Photo: University of Illinois at Chicago. Used with permission. Photo: University of Illinois at Chicago. Used with permission. Additional Investigations Chest X-ray Chest CT imaging Lung volumes and diffusing capacity Oximetry and arterial blood gases Alpha-1 antitrypsin deficiency screening Exercise testing Composite scores 10

11 COPD and Comorbidities Common comorbidities of COPD: Cardiovascular disease Heart failure Arrhythmias Diabetes Depression/Anxiety Osteoporosis Lung cancer Sleep disorders Anemia GERD Obstructive sleep apnea COPD has significant extrapulmonary (systemic) effects including: Weight loss/gain Nutritional abnormalities Skeletal muscle dysfunction Treatment Treatment: Nonpharmacologic Approaches Smoking cessation Avoidance of indoor and outdoor pollutants Vaccinations Optimizing nutrition Pulmonary rehabilitation Exercise training Oxygen therapy Surgical and bronchoscopic interventions Education and self-management End of life and palliative care 11

12 Smoking Cessation Brief counseling is effective; provide at every visit Counseling and pharmacotherapy more effective together than either alone First-line pharmacotherapies: Oral: varenicline, bupropion Nicotine replacement therapy: gum, inhaler, nasal spray, patch, lozenges 5 A s Ask, Advise, Assess, Assist, Arrange 5 R s Relevance, Risk, Rewards, Roadblocks, Repetition Agency for Healthcare Research and Quality. 4 D s Delay, Deep Breath, Drink Water, Do Something Else Pulmonary Rehabilitation and Home Exercise Pulmonary rehab (PR) is the most effective therapeutic strategy to improve shortness of breath, health status and exercise tolerance Reduces readmissions and mortality Among the most costeffective strategies Clinician tips for promoting exercise and activity in COPD Take all meds as prescribed Avoid prolonged sitting Make exercise routine Warm up, cool down, don t over-do it Start slowly and increase speed or mileage daily Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2018 Report. Corbridge SJ, Nyenhuis SM. J Nurse Pract. 2017;13(1): Photo: University of Illinois at Chicago. Used with permission. COPD Inhaler Classes Short-acting beta-2 agonists (SABA) Short-acting muscarinic receptor antagonists (SAMA) Combination SABA/SAMA Long-acting beta-2 agonists (LABA) Long-acting muscarinic receptor antagonists (LAMA) Inhaled corticosteroids (ICS) Combination LAMA/LABA Combination ICS/LABA Combination ICS/LABMA/LABA 12

13 COPD Medications For a complete list, please refer to the appendix provided in the activity materials: Bronchodilators in Stable COPD GOLD Recommendation Inhaled bronchodilators in COPD are central to symptom management and commonly given on a regular basis to prevent or reduce symptoms Regular and as-needed use of SABA or SAMA improves FEV1 and symptoms Combinations of SABA and SAMA are superior to either medication alone in improving FEV1 and symptoms LABAs and LAMAs significantly improve lung function, dyspnea, health status, and reduce exacerbation rates LAMAs have a greater effect on exacerbation reduction compared with LABAS LAMAs have a greater effect decreased hospitalizations compared with LABAS Evidence Level A = Randomized controlled trials, rich body of high quality evidence without any significant limitation or bias B = Randomized controlled trials with important limitations, limited body of evidence A A A A A B Bronchodilators in Stable COPD GOLD Recommendation Combination treatment with a LABA and LAMA increases FEV1 and reduces symptoms compared to monotherapy Combination treatment with a LABA and LAMA reduces exacerbations compared to monotherapy or ISC/LABA Tiotropium improves the effectiveness of pulmonary rehabilitation in increasing exercise performance Theophylline exerts a small bronchodilator effect in stable COPD Theophylline is associated with modest symptom benefits in stable COPD Evidence Level A B B A B A = Randomized controlled trials, rich body of high quality evidence without any significant limitation or bias B = Randomized controlled trials with important limitations, limited body of evidence 13

14 Pharmacologic Treatment Algorithms by GOLD Grade 2018 Global Initiative for Chronic Obstructive Lung Disease, Inc. Used with permission. Do not reproduce in print. Inhaler Technique is Key Patients frequently misuse inhalers 1-4 Health care providers misuse inhalers 5-6 Guidelines recommend review of technique at each visit 7 1.Batterink J, et al. CN J Hosp Pharm. 2012;65(2): Melani AS, et al. Respir Med. 2011;105(6): Press VG, et al. J Gen Intern Med. 2012;27(10): Sestini P, et al. J Aerosol Med. 2006;19(2): Lalani NS, et al. Health. 2012;3(1): De Tratto K, et al. 2014;28(3): How to Use Inhalers How to Use Inhalers: Used with permission. 14

15 Additional Medications Phosphodiesterase-4 inhibitors Azithromycin and erythromycin Systemic corticosteroids Alpha-1 antitrypsin augmentation therapy Low dose long acting opioids Methylxanthines Bone sparing agents Antidepressants Laurin C, et al. Am J Respir Crit Care Med. 2012;185(9): Cafarella PA, et al. Respirology. 2012;17(4): Adherence Adherence to COPD therapy is often poor 1 Fewer than half of treatments for COPD are taken as prescribed Nonadherence contributes to hospitalization, death, and healthcare costs Nonadherence or poor adherence can be caused by: 2,3 Inadequate patient knowledge of disease or treatments Side effects Poor inhaler technique (unintentional) Cost 1.Bender BG. Curr Opin Pulm Med. 2014;20(2): Spencer P and Hanania NA. J Multidiscip Healthc. 2013;6: Sriram KB and Percival M. Chron Respir Dis. 2016;13(1): Assessing Adherence Method Advantages Disadvantages Clinician estimates Easy to obtain Unreliable Patient self-report Easy to obtain Unreliable Pill counts/weighing Easy to obtain Overestimates use Pharmacy records Confirms prescription filling Incomplete, biased estimates Biologic measures Electronic monitoring Confirms ingestion Confirms patterns of use, ingestion Expensive, invasive, insensitive to inhaled drugs, affected by pharmacokinetics and polypharmacy Expensive, limited availability and use, malfunctions Lareau SC and Yawn BP. Int J Chron Obstruct Pulmon Dis. 2010;5: Red flags for poor adherence Denial Patient beliefs about illness and treatment Disruption Personal and family crises Depression Apathy and withdrawal Dementia Psychiatric or related to substance abuse 15

16 Improving Adherence Matching Adherence Interventions to the Type of Nonadherence Type of nonadherence Adherence intervention Erratic Simplify and tailor regimen Implement behavioral strategies such as cueing, reminders, and reinforcement Self-monitoring and support, with monitoring from others Unwitting Review of adherence behavior Written or visual medication plans Patient education in disease management Intelligent Patient education and counseling Negotiate therapy Link therapy with personal goals Lareau SC and Yawn BP. Int J Chron Obstruct Pulmon Dis. 2010;5: Case MP: 55-year-old investment banker Presents with: Shortness of breath and increased sputum production (2 teaspoons clear phlegm each morning) Dyspnea on exertion: 1-2 blocks/1 flight stairs No prior respiratory-related hospitalizations or ED visits but internist gave her albuterol several months ago uses several times a week with some relief Started smoking age 15; smokes 2 packs per day No other significant past medical history Photo: University of Illinois at Chicago. Used with permission. Case, cont d. Vital signs BP: 138/78 mmhg; HR: 88 beats per minute; RR: 22 breaths per minute; afebrile; BMI: 21; O2 saturation at rest: 94% No acute distress Cardiac exam unremarkable Lungs Diminished breath sounds Prolonged expiratory phase Scattered end-expiratory wheezing No peripheral edema; no clubbing 16

17 Case, cont d. Spirometry (post-bronchodilator): FEV1/FVC: 0.65 FEV1: 60% predicted COPD assessment test (CAT) score: 17 6 minute hall walk: 1000 feet with no desaturation Case: GOLD ABCD Assessment Tool 2018 Global Initiative for Chronic Obstructive Lung Disease, Inc. Used with permission. Do not reproduce in print Global Initiative for Chronic Obstructive Lung Disease, Inc. Used with permission. Do not reproduce in print. 17

18 Additional Recommendations by Group Patient Group Essential Recommended A Smoking cessation Physical activity Flu and pneumonia vaccines B-D Smoking cessation Pulmonary rehabilitation Physical activity Acute Exacerbations Potential Causes of Exacerbations Respiratory viral infections or (less often) bacterial infections Environmental factors Pollution Ambient temperature Short-term exposure to fine particulate matter 18

19 Prevention of Exacerbations Prevention of exacerbations is key Lung function may never recover to baseline Frequent exacerbators have worse outcome and morbidity Available tools to help prevent exacerbations: Pharmacotherapy Patient education Vaccinations Pulmonary rehabilitation Corbridge S, et al. Am J Nurse. 2012;112(3): Recognizing Acute Exacerbations Defined as an acute worsening of respiratory symptoms that result in additional therapy Associated with increased airway inflammation, increased mucus production, and marked gas trapping Symptoms include: Dyspnea Increased sputum purulence and volume Increased cough and wheeze Symptoms typically last 7-10 days, but may last longer 20% of patients have not recovered to their preexacerbation state at 8 weeks When to Hospitalize Potential indications for hospital assessment: Severe symptoms Sudden worsening of resting dyspnea High respiratory rate Decreased oxygen saturation Confusion and/or drowsiness Acute respiratory failure Onset of new physical signs (eg, peripheral edema) Failure of an exacerbation to respond to initial medical management Presence of serious comorbidities (eg, heart failure, newly occurring arrhythmias, etc.) Insufficient home support 19

20 Management of Exacerbations Pharmacotherapy and optimizing oxygenation and ventilation are cornerstones of management More than 80% of patients can be treated at home Treatment options: Bronchodilators Glucocorticoids Antibiotics Respiratory support GOLD Recommendations for Management of Exacerbations GOLD Recommendation SABA with or without short-acting anticholinergics are recommended as the initial bronchodilators to treat an acute exacerbations Systemic corticosteroids can improve lung function (FEV1), oxygenation, and shorten recovery time and hospitalization duration. Duration of therapy should not be more than 5-7 days Antibiotics, when indicated, can shorten recovery time, reduce the risk of early relapse, treatment failure, and hospitalization duration. Duration of therapy should not be more than 5-7 days Methylxanthines are not recommended due to increased side effect profiles Non-invasive mechanical ventilation (NIV) should be the first mode of ventilation used in COPD patients with acute respiratory failure who have no absolute contraindication Evidence Category A = Randomized controlled trials, rich body of high quality evidence without any significant limitation or bias; B = Randomized controlled trials with important limitations, limited body of evidence; C = non-randomized trials, observational studies C A B B A Summary COPD is a major source of morbidity and mortality in the US and worldwide Chronically underreported Exacerbations and comorbidities negatively impact prognosis Diagnose by symptoms and exposure Use spirometry to confirm Assess patient impact CAT, MMRC, CCQ Use the GOLD ABCD assessment tool 20

21 Summary Use both pharmacological and nonpharmacological treatment options to manage COPD Prevent exacerbations Assess inhaler technique Assess patient adherence Most acute exacerbations can be managed at home Know when to hospitalize patients 21

22 Comprehensive Care in COPD: Strategies for Nurse Practitioners References Asthma, COPD, and Asthma-COPD Overlap Syndrome. The Global Initiative for Chronic Obstructive Lung Disease. Published Batterink J, Dahri K, Aulakh A, Rempel C. Evaluation of the use of inhaled medications by hospital in patients with chronic obstructive pulmonary disease. Can J Hosp Pharm Mar;65(2): Bender B G. Nonadherence in chronic obstructive pulmonary disease patients: what do we know and what should we do next? Curr Opin Pulm Med Mar;20(2): Cafarella PA, Effing TW, Usmani ZA, Frith PA. Treatments for anxiety and depression in patients with chronic obstructive pulmonary disease: a literature review. Respirology May;17(4): Corbridge SJ, Nyenhuis SM. Promoting Physical Activity and Exercise in Patients with Asthma and Chronic Obstructive Pulmonary Disease. J Nurse Pract. 2017;13(1): Corbridge S, Wilken L, Kapella MC, Gronkiewicz C. An evidence-based approach to COPD: part 1. Am J Nurs Mar;112(3):46-57; quiz 59,58. COPD Assessment Test. COPD Assessment Test Website. Published February 24,2012. Updated October COPD Diagnosis and Management At-A-Glance Desk Reference The Global Initiative for Chronic Obstructive Lung Disease. Deaths and Mortality-National Center for Health Statistics. Centers for Disease Control and Prevention. Published May 3, De Tratto K, Gomez C, Ryan C, Bracken N, et al. Nurses Knowledge of Inhaler Technique in the Inpatient Hospital Setting. Clin Nurse Spec: May/June 2014 May/June;28 (3): GOLD Spirometry Guide. The Global Initiative for Chronic Obstructive Lung Disease. Published Lalani NS. A study of knowledge assessment and competence in asthma and inhaler technique of nurses employed at university teaching hospital. thehealth. 2012;3(1): Lareau SC, Yawn BP. Improving adherence with inhaler therapy in COPD. Int J Chron Obstruct Pulmon Dis Nov 24;5: Laurin C, Moullec G, Bacon SL, Lavoie KL. Impact of anxiety and depression on chronic obstructive pulmonary disease exacerbation risk. Am J Respir Crit Care Med May 1;185(9): Melani A, Bonavia M, Cilenti V, Cinti C, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med Jun;105(6):

23 Pocket Guide to COPD Diagnosis, Management, and Prevention The Global Initiative for Chronic Obstructive Lung Disease Feb-Final-to-print-v2.pdf. Published December Press V G, Arora V M, Shah L M, Lewis S L, et al. Teaching the use of respiratory inhalers to hospitalized patients with asthma or COPD: a randomized trial. J Gen Intern Med Oct;27(10): Sestini P, Cappiello V, Aliani M, Martucci P, et al. Prescription bias and factors associated with improper use of inhalers. J Aerosol Med Summer;19(2): Spencer P, Hanania NA. Optimizing safety of COPD treatments: role of the nurse practitioner. J Multidiscip Healthc. 2013;6: Sriram KB, Percival M. Suboptimal inhaler medication adherence and incorrect technique are common among chronic obstructive pulmonary disease patients. Chron Respir Dis Feb;13(1): Taking Her Breath Away: The Rise of COPD in Women. American Lung Association. Published June Treating Tobacco Use and Dependence: 2008 Update. Agency for Healthcare Research and Quality. Published August Updated January 2018.

24 Appendix: COPD Medication Table SHORT-ACTING BRONCHODILATORS Short-Acting Beta2-Agonists (SABA) Short-Acting Muscarinic Antagonists (SAMA) Combination SABA/SAMA Drug Albuterol Levalbuterol Ipratropium Albuterol/Ipratropium Product Ventolin HFA ProAir HFA Proventil HFA MDI 90 mcg Nebulizer Solution 2.5 mg/3 ml (0.083%) vial Xopenex HFA MDI 45 mcg Nebulizer Solution 1.25 mg/3ml vial Atrovent HFA 17 mcg/puff Nebulizer Solution 500 mcg (2.5 ml) per vial Combivent SMI Respimat Albuterol 100 mcg/ Ipratropium 20 mcg DuoNeb Nebulizer Solution Albuterol 3mg/ Ipratropium 0.5mg vial Image Dosing 1-2 puffs Q4-6h PRN 2.5 mg Q4-6h PRN 1-2 puffs Q4-6h PRN 1.25 mg Q4-6h PRN 2 puffs Q6-8h PRN 500 mcg Q6-8h 1 inhalation Q6h PRN PRN 3 ml Q6h Use Preferred use Group A without persistent dyspnea Treatment of an exacerbation Adverse Effects Tremor, nervousness, palpitations, tachycardia, hypokalemia, insomnia, hyperglycemia Dry mouth, metallic taste, constipation, urinary retention, tachycardia, blurred vision, precipitation of narrow angle glaucoma, increased CV events See Individual SEs Advantages Reduces symptoms, temporary increase in FEV 1, increased exercise endurance Combo provides greater change in spirometry than either agent alone. Improved adherence Disadvantages Lack of clinical studies to support use in Group A Response varies by patient and may be less than SAMA Lung Health Study showed no effect on decline in FEV 1 See Individual SEs Developed by Lori Wilken, PharmD. Used with permission.

25 LONG-ACTING BRONCHODILATORS Long-Acting Muscarinic Antagonists (LAMA) Drug Tiotropium Aclidinium Umeclidinium Glycopyrrolate Product Spiriva Respimat Spiriva Handihaler DPI Tudorza Pressair DPI Incruse Ellipta DPI Seebri Neohaler 2.5 mcg 18 mcg 400 mcg 62.5 mcg 15.6 mcg Image Dosing Use Adverse Effects Advantages 2 inhalations DAILY 1 capsule for inhalation DAILY 1 inhalation BID Preferred use Alone in Group A, Group B, or Group C Use with LABA in Group D Step up With LABA in Groups B and C With LABA and ICS in Group D 1 inhalation DAILY Dry Mouth, blurred Vision, constipation, urinary retention, worsening glaucoma Decreases exacerbations and hospitalizations Improves symptoms Dosed once daily Gold standard COPD medication Approved for asthma Locking mechanism after last dose Propellant free (Respimat) Decreases hospitalizations Improves symptoms Indicator window for proper dose delivery Improved QOL and FEV1 Quick onset 1 capsule for inhalation BID Decreases exacerbations and hospitalizations Improves symptoms Disadvantages Difficult to assemble Twisting may be difficult for patients with low dexterity More side effects with CrCl <60 Capsule for inhalation may be confusing and/or challenging, especially with poor dexterity Product phasing out Difficulty with using unique inhaler Lacks evidence for use Capsule for inhalation may be confusing and/or challenging, especially with poor dexterity Developed by Lori Wilken, PharmD. Used with permission.

26 LONG-ACTING BRONCHODILATORS Ultra-Long-Acting Beta 2 -Agonists (LABA) Long-Acting Beta 2 -Agonists (LABA) Drug Indacaterol Olodaterol Salmeterol Formoterol Arformoterol Product Arcapta Neohaler DPI 75 mcg Striverdi Respimat 2.5 mcg Serevent Diskus DPI 50 mcg Perforomist 20 mcg/2ml Brovana Nebulization Solution 15 mcg/2ml Image Dosing 1 capsule for inhalation DAILY 2 inhalations DAILY 1 inhalation BID 1 vial BID 1 vial BID Use Adverse Effects Dry Mouth Tremor Chest pain Blurry vision Sore throat Headache Cough Nasopharyngitis Hypokalemia Hyperglycemia Nasopharyngitis Back pain Bronchitis Cough QTc prolongation Upper respiratory tract infection Hypokalemia Hyperglycemia Preferred use Alone in Group A or Group B Use with LAMA or ICS in Group D Step up With LAMA in Groups B and C With LAMA and ICS in Group D Group C/D: combined with ICS or with LAMA Cough Headache Pharyngitis Upper respiratory tract infections Musculoskeletal pain Throat irritation Hypokalemia Hyperglycemia Nausea Diarrhea Dry mouth Tremor Hypokalemia Hyperglycemia Pain Chest pain Skin rash Diarrhea Nonspecific pain Sinusitis Backache Hypokalemia Hyperglycemia Individual Advantages Improves breathlessness, health status, and exacerbation rates Studied at higher doses of 150 and 300 mg daily Improves FEV1 and symptoms Improves FEV1, dyspnea, QOL, Decreases hospitalizations and exacerbations Improves FEV1, dyspnea, QOL, Decreases hospitalizations and exacerbations No coordination Covered by Medicare Improved FEV1 No coordination Covered by Medicare Overall precaution Avoid use alone in asthma Developed by Lori Wilken, PharmD. Used with permission.

27 Long-Acting Muscarinic Antagonist (LAMA)/ Long Acting Beta 2 -Agonists (LABA) Drug Umeclidinium/Vilanterol Indacaterol/Glycopyrrolate Tiotropium/Olodaterol Glycopyrrolate/Formoterol Product Anoro Ellipta DPI 62.5 mcg/25 mcg Utibron Neohaler 27.5 mcg/15.6 mcg Stiolto Respimat 2.5 mcg/2.5 mcg Bevespi Aerosphere 9 mcg/4.8 mcg Image Dosing 1 inhalation DAILY 1 inhalation BID 2 inhalations DAILY 2 inhalations BID Use Preferred use Group D Step up Group B, Group C In combination with ICS for Group D Adverse Effects Pharyngitis Sinusitis Upper respiratory tract infection Nasopharyngitis Hypertension Headache Nasopharyngitis Back pain Backache Cough Urinary tract infection Individual Advantages Overall precautions Disadvantages Improved FEV1 at 6 months Umeclidinium reversibly inhibits M3 receptor Best evidence Improved FEV1 at 52 weeks. Improved QOL Decreases exacerbations Improved FEV1 at 52 weeks Tiotropium inhibits M1 to M5 receptors Improved FEV1, QOL and decreased albuterol use at 6 months Glycopyrrolate inhibits M1 to M5 receptors Worsening narrow angle-glaucoma, BPH, arrhythmias, hypertension, seizures, hyperglycemia and hypokalemia Breath actuated Good for only 6 weeks after opening the foil packaging Requires capsules - may be difficult for patients with low dexterity Twisting may be difficult for patients with low dexterity Moderate-severe renal impairment may worsen side effects Prime after 3 days of not using inhaler Coordinated actuation and inhalation required Prime inhaler after 7 days of not using the inhaler Developed by Lori Wilken, PharmD. Used with permission.

28 ANTI-INFLAMMATORY AND BRONCHODILATOR Inhaled Corticosteroids (ICS)/ Long Acting Beta 2 -Agonists (LABA) Drug Budesonide/ Formoterol Fluticasone Propionate/ Salmeterol Fluticasone Propionate/ Salmeterol Fluticasone Furoate/ Vilanterol Product Symbicort HFA MDI 160/4.5 mcg Advair Diskus DPI 250/50 mcg Advair HFA MDI 115/21 mcg Breo Ellipta DPI 100/25 mcg Image Dosing 2 inhalations BID 1 inhalation BID 2 inhalations BID 1 inhalation DAILY Use Preferred Use Asthma + COPD Group D Step-up Group C or with LAMA in Group D Adverse Effects Candidiasis (thrush): counsel patient to rinse out mouth; dysphonia; pneumonia; skin bruising; osteoporosis; cataracts; TB Overall Advantages Decreases exacerbations and hospitalizations and improves QOL Increased risk of mortality and pneumonia reported in the TORCH trial (fluticasone propionate alone) Increased risk of pneumonia with fluticasone propionate/salmeterol TORCH trial Overall Disadvantages Risk factors for pneumonia not dose dependent (current smokers, prior pneumonia, BMI <25 kg/m 2, FEV1 30%-<50%, poor MRC dyspnea score) Check for drug interactions Developed by Lori Wilken, PharmD. Used with permission.

29 ALTERNATIVE STEP-UP MEDICATIONS Drug Azithromycin Erythromycin Roflumilast Product Azithromycin 250 mg Erythromycin Stearate 250 mg Daliresp Tablets 500 mcg Image Dosing 250 mg/day or 500 mg 3X/week 250 mg BID 500 mcg PO DAILY Use Step-up Group D added to LAMA+LABA+ICS Step-up Group D added to LAMA+LABA+ICS Step-up Group D added to LAMA+LABA+ICS Adverse Effects Bacterial resistance and hearing test impairments QT prolongation Hepatotoxic N/V, diarrhea C. difficile, diarrhea nausea, vomiting, cramps Hearing loss QT prolongation Diarrhea, weight loss, nausea, headache, abdominal pain, sleep disturbances Individual Advantages Decreases exacerbations Decreases exacerbations Decreases exacerbations Prevents hospitalizations Improves symptoms and QOL Disadvantages Not effective in current smokers Limited studies Contraindicated: Moderate/severe liver impairment Not used in emphysema Avoid use with theophylline CYP 3A4 substrate Caution In: Cancer patients, latent infections, immunologic disorders/ immunosuppressant medications, depression or SI Developed by Lori Wilken, PharmD. Used with permission.

30 COPD Severity Group COPD SEVERITY C D LAMA LAMA + LABA Exacerbations in the Past 12 Months >2 or any COPD related hospitalizations Group A B Recommended First Choice SAMA prn, SABA prn, LABA, LAMA or SABA and SAMA prn LAMA or LABA Step Up LAMA or LABA LAMA and LABA Step Up Alternative Class Alternative Class A SAMA or SABA or LAMA or LABA CAT <10 or mmrc 0-1 Few symptoms B LAMA or LABA CAT <10 or mmrc >2 Many symptoms 1 or less and not leading to hospitalization C D LAMA LAMA + LABA or LABA+ICS LAMA + LABA or LABA+ICS LAMA and LABA and ICS LAMA and Roflumilast LABA and Roflumilast LAMA + LABA + ICS Roflumilast Azithromycin ICS Withdraw Developed by Lori Wilken, PharmD. Used with permission.