Women Beware The Threat of COPD

Page 1 Women Beware The Threat of COPD Catherine E. Cooke, PharmD, BCPS, PAHM President, PosiHealth, Inc. & Clinical Associate Professor, University of Maryland School of Pharmacy Supported by an education grant from Boehringer Ingelheim Women Beware The Threat of COPD Speaker: Catherine Cooke attained her Bachelor in Pharmacy from the University of Iowa and then went on to receive her Pharm.D. from the Medical University of South Carolina. Subsequently, she completed a specialty residency in Ambulatory Care/Managed Care through the Philadelphia College of Pharmacy and Science. After post-graduate training, Dr. Cooke served as a full-time Assistant Professor at the University of Maryland School of Pharmacy where she became a Board Certified Pharmacotherapy Specialist. Currently, she is an Independent Consultant working in health care quality and research. In addition, she provides clinical pharmacy services such as hypertension, dyslipidemia and smoking cessation management to patients in Maryland. Her main research interests are in the areas of cardiovascular pharmacotherapeutics and pharmacy services in the managed care environment with specific interest in discrepancies in health care based on sex or ethnicity. Speaker Disclosure: Dr. Cooke has no actual or potential conflicts of interest in relation to this program Supported by an education grant from Boehringer Ingelheim PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Accreditation: Pharmacists 798-000-09-028-L01-P Pharmacy Technicians 798-000-09-028-L01-T Target Audience: Pharmacists & Technicians Women Beware The Threat of COPD CE Credits: 1.0 Continuing Education Credit or 0.1 CEU for pharmacists/technicians Expiration Date: 05/27/2012 Program Overview: Women have made a good deal of welcome progress in the last several decades, but at least one advance is unwanted: chronic obstructive pulmonary disease (COPD) is on the rise in women in prevalence, morbidity and mortality. By 2000, the number of women dying from COPD surpassed the number of men. But the rising number of cases in women has not been matched by medical understanding of the disease's apparent gender-bias. This program will increase the awareness of COPD in women. The program will focus on the pharmacists role in identifying patients with COPD (women in particular), reducing the risk factors for developing COPD (such as smoking cessation), and managing the disease. Objectives: Review the etiology and epidemiology of chronic obstructive pulmonary disease (COPD) in women. Identify the impact of COPD on women and the differences in how the disease manifests itself in women compared to men. Provide an update on the efficacy, safety, and role of available treatments in the management of COPD. Describe how pharmacist s can play a critical role in COPD identification, management and education (particularly with women). Supported by an education grant from Boehringer Ingelheim Learning REVIEW the etiology Objectives and epidemiology of chronic obstructive pulmonary disease (COPD) in women. IDENTIFY the impact of COPD on women and the differences in how the disease manifests itself in women compared to men. PROVIDE an update on the efficacy, safety, and role of available treatments to manage COPD. DESCRIBE how pharmacist s can play a critical role in COPD identification, management and education (particularly with women). PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education

Page 2 Chronic obstructive pulmonary disease (COPD) Characterized by airflow limitation Not fully reversible Usually progressive Used to be looked upon as 2 diseases chronic bronchitis and emphysema but usually conditions coexist Chronic bronchitis Bronchial tubes are inflamed and eventually scarred Emphysema Alveoli are irreversibly damaged and lose elasticity 1. Rennard SI. COPD: overview of definitions, epidemiology, and factors influencing its development. Chest 1998;113(Suppl 4):235--41s. COPD Asthma Age of onset Usually >40 years Any age (usually < 40 years) Smoking History Symptom Pattern Airway Reversibility Steroid response in stable disease Usually > 20 packyears Usually chronic, slowly progressive Partially reversible Unusual (~15% - 20%) Unrelated Varies day by day Nocturnal/early morning Largely reversible Present Clinical Presentation of COPD Symptoms Chronic cough Sputum production Shortness of breath leading to chronic fatigue, decreased exercise capacity and increased respiratory exacerbations Consequences Respiratory failure Cor pulmonale (right sided heart failure) Respiratory exacerbations become life-threatening Spirometry Lung function reported as percent of predicted values for a normal population Terminology FEV 1 = forced expiratory volume in 1 second FVC = forced vital capacity

Liters Page 3 COPD Defining Characteristics Spirometric diagnostic criteria Reduced forced expiratory volume in 1 second FEV 1 < 80% Spirometry: Volume/Time Curve 1 2 FEV 1 Normal 4.15 COPD FEV 1 FVC FEV 1 / FVC 5.2 > 80% 2.35 3.9 < 70% Reduced ratio of FEV 1 to FVC 3 COPD FEV 1 /FVC < 70% 4 FEV 1 FVC 5 Normal FVC 1 2 3 4 5 6 Seconds Diagnosis of COPD in Women Diagnosis of COPD in Women 80 Spirometry % Diagnosed 70 60 50 40 30 20 10 0 Clinical presentation Spirometry Primary care physicians underutilize spirometry Women less likely to receive referrals to specialists than men Study: Confronting COPD Survey Women less likely to have spirometry than men (OR 0.84; 95% CI 0.72-0.98) Female case Male case

Number Deaths x 1000 Page 4 Epidemiology Estimated 24 million adults with COPD in US COPD Mortality by Gender, U.S., 1980-2000 70 60 COPD - 4 th leading cause of death in the US 1 Hospitalization: Hospitalization rates greater for women than men since 1993 Mortality worse in women 1. National Center for Health Statistics. Deaths: final data for 1999. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. National Vital Statistics Report 2001;49:1 116. 2. American Lung Association Epidemiology and Statistics Unit Research and Program Services. Trends in COPD(Chronic Bronchitis and Emphysema); Morbidity and Mortality. American Lung Association Website. http://lungusa.org. Accessed march 14 th, 2009. 50 40 30 20 10 0 Men Women 1980 1985 1990 1995 2000 US Centers for Disease Control and Prevention, 2002 Risk Factors - Smoking Tobacco use is the #1 cause of COPD 1 75% of deaths from COPD resulted from smoking in 2005 Cigarette smokers vs. nonsmokers 2 Greater annual decrease in FEV1 More respiratory symptoms Higher death rates Women more susceptible to smoke? Meta-analysis: Women who smoke had significantly faster annual decline in FEV1% predicted with increasing age vs. men who smoke Lung Health Study Increase in # of cigarettes resulted in larger decline in FEV1 than men Why? 1. Centers for Disease Control and Prevention (CDC). Deaths from chronic obstructive pulmonary disease--united States, 2000-2005. [Journal Article] MMWR - Morbidity & Mortality Weekly Report. 57(45):1229-32, 2008 Nov 14. 2. American Lung Association Epidemiology and Statistics Unit Research and Program Services. Trends in COPD(Chronic Bronchitis and Emphysema); Morbidity and Mortality. American Lung Association Website. http://lungusa.org. Accessed march 14 th, 2009.

Page 5 Other Risk Factors Genetic severe heredity deficiency of alpha-1 antitrypsin Occupational dust and chemicals Pollution indoor (biomass cooking) and outdoor (urban pollution) Infection severe childhood respiratory infection Women who smoke during pregnancy decrease lung growth in utero 1. American Lung Association Epidemiology and Statistics Unit Research and Program Services. Trends in COPD (Chronic Bronchitis and Emphysema): Morbidity and Mortality. American Lung Association Website. http://lungusa.org. Accessed March 14 th, 2009. Consensus Guidelines GOLD Global Initiative for Chronic Obstructive Lung Disease 1 US National Heart, Lung and Blood Institute and World Health Organization joint committee First published in 2001 Last revision published 2008 Covers diagnosis, management and prevention Does not differentiate diagnosis and management between men 1. National and Heart, Lung, women and Blood Institute and World Health Organization. Global initiative for chronic obstructive lung disease: global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2008 update. Available at: www.goldcopd.com. Accessed March 15 th,2009. Treatment Pathway Consensus Guidelines - Diagnosis I: Mild COPD FEV1/FVC < 70% FEV1 >= 80% predicted II: Moderate COPD FEV1/FVC < 70% 50% <= FEV1 < 80% predicted III: Severe COPD FEV1/FVC < 70% 30% <= FEV1 < 50% predicted IV: Very Severe COPD FEV1/FVC < 70% FEV1 <30% predicted or FEV1< 50% predicted plus chronic respiratory failure (Respiratory Failure: arterial partial pressure of oxygen PaO2 less than 60mmHg with or without PaCO2 greater than 50mmHg 1. Pauwels et. Al. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001 Apr;163(5):1256-76.

Page 6 Non Pharmacologic Therapy Smoking Cessation Vaccines Flu: Annual influenza vaccine Pneumococcal polysaccharide vaccine Age 65 or older <65 years and FEV1 <40% predicted

Page 7 Broncholilators Central to symptomatic management PRN or scheduled based on severity Inhaled route preferred fewer adverse effects Includes: β2- agonists, anticholinergics and methylxanthines All increase exercise capacity Long-acting forms more effective and convenient Short Acting β2- agonists Medication Brand Generic Availability Dosage FDA approval Directions Class Form Bronchodilator- Proventil Albuterol Brand only Inhaler No -asthma, 2 inhalationsevery 4 6 Short acting B2- bronchitis hours agonist Ventolin Albuterol Brand only Inhaler No -asthma 2 inhalations every 4 6 hours Proair Albuterol Brand only Inhaler No -asthma 2 inhalations every 4 6 hours Xopenex levalbuterol Brand only Inhaler No - asthma 2 inhalations every 4 6 hours Maxair Pirbuterol Brand only Inhaler Yes 2 inhalations every 4 6 hours Class Side Brethine Terbutaline Generic only Tablets Yes, also asthma 5 mg PO three times daily Effects: dry mouth, irritated Alupent Metaproterenol Generic only nebulizing Yes 0.2 0.3 ml of 5% (10 15 throat, trembling, solution mg) solution, diluted in 2.5 nervousness, 3 ml of 1/2 NS, NS, or other dizziness, diluents or, 2.5 ml of 0.4 headache, 0.6% solution (10 15 mg). palpitations, Doses may be repeated 3 4 nausea, vomiting times per day 2.5 5 mg initially Accuneb Albuterol solution Generic only nebulizing No -asthma, every 20 solution bronchitis minutes for 3 doses, then 2.5 10 mg every 1 4 hours as needed

Page 8 Long Acting β2- agonists Anticholinergics Medication Class Brand Generic Availability Dosage Form FDA approval Directions Medication Class Brand Generic Availability Dosage Form FDA approval Directions Bronchodilator- Long acting B2- agonist Foradil Formoterol Brand only Aerolizer Yes, also asthma Inhale 12 mcg (contents of one capsule) every 12 hours using the Aerolizer Anitcholinergics- Atrovent ipratropium Brand only Inhaler Yes, also asthma 2 sprays (18 mcg/spray) Short and long 3 4 times per day acting Serevent Salmeterol Brand only Diskus Yes, also asthma 50 mcg (1 oral inhalation) of salmeterol twice daily Class Side Effects: dry mouth, irritated throat, trembling, Perforomist Formoterol Brand only Nebulizing Yes, also asthma One 20 mcg unit dose nervousness, solution vial administered by dizziness, nebulization twice daily in headache, the morning and evening palpitations, nausea, vomiting Class Side Spiriva tiotropium Brand only Handihaler Yes 18 mcg once per day via Effects: oral inhalation Dry mouth, blurred vision, Ipitropiuim ipratropium Generic only Nebulizing Yes, also asthma 500 mcg (1 unit dose vial) constipation, runny solution solution 3 4 times per day via nose, irritated oral nebulization throat, runny nose, AntiCholinergics & CV Risk? Theophylline Meta-Analysis to assess CV risks associated with >30 day use of ipratropium and tiotropium vs. control in patients with COPD 17 RCT with 7472 on anticholinergics and 7311 on control Results: Inhaled anticholinergics significantly increased: Risk of CV death, non-fatal MI or stroke, RR 1.58 (95% CI, 1.21-2.06) MI, RR 1.53, (95% CI 1.05-2.23) CV death, RR 1.80 (95% CI 1.17-2.77) Stroke NOT significantly increased Secondary outcome - risk of all-cause mortality NS difference Need prospective RCT to accurately access CV risk Low dose theophylline reduces exacerbations but does not increase post-bronchodilator lung function Higher does are effective bronchodilators, but may cause toxicity Theophylline Dosing 150mg BID increase to 200mg BID after 3 days, Then 300mg BID after 3 days or 300-400 QD then 400-600mg QD Titrate according to blood level

Page 9 Steroids Regular treatment does not modify long term decline Increases likelihood of pneumonia, does not decrease mortality Reduce exacerbations in Severe COPD and Very Severe COPD FEV1<50% predicted If needed, combination products with anticholinergic synergistic Inhaled Steroids Medication Class Inhaled Corticosteroids Class Side Effects: dry mouth, hoarseness, throat infection, oral candidiasis Brand Generic Availability Dosage Form FDA approval Directions Qvar beclomethasone Brand only Inhaler No - asthma 40 80 mcg (1 2 sprays) inhaled orally twice daily Pulmicort budesonide Brand only Flexhaler No - asthma 360 mcg twice daily by oral inhalation Pulmicort budesonide Brand/Generic Nebulizing No - asthma For children: 0.5 mg/day Respules solution inhaled via jet nebulizer either once daily or divided into 2 doses Flovent fluticasone Brand only Diskus Yes, also asthma 1 inhalation twice daily Alvesco Ciclesonide Brand only Inhaler No, asthma, allergies 1 inhalation twice daily Asmanex Brand only Twisthaler No, asthma 1 inhalation twice dialy Azmacort triamcinolone Brand only Inhaler No - asthma Initially, 150 mcg (2 inhalations) PO 3 4 times per day or 300 mcg (4 inhalations) PO twice daily. Aerobid flunisolide Brand only Inhaler No- asthma 2 sprays (250 mcg/spray) via oral inhalation twice daily Combination Products Brand Generic Availability Dosage Form FDA approval Directions Combivent albuterol/ipratropium Brand only Inhaler Yes, also asthma Inhale 2 actuations four times per day Advair salmeterol/fluticasone Brand only Diskhaler Yes, also asthma 1 inhalation twice a day Duoneb albuterol/ipratropium Brand/generic Nebulizing solution Yes, also asthma Inhale one 3 ml vial via nebulizer four times per day Symbicort budesonide/formoterol Brand only Inhaler Yes, also asthma 2 inhalations of Symbicort 160/4.5 (160 mcg of budesonide and 4.5 mcg of formoterol per inhalation) twice daily Pharmacist s Role Inquire about and recommend spirometry Smoking cessation counseling at every visit Nutrition counseling Preventing infections hand washing, vaccinations Recognizing exacerbations Education Depression and anxiety screening Support groups

Page 10 Pharmacist s Role Training patients to use inhalers is crucial 1 : 1. Mourad RE, Hagerman JK. Management Strategies in Stable COPD. US Pharmacist.2009;34-HS-10-HS-18. Jan 26 2009. 66 yo woman visits PCP for a lingering cough after having a cold Subjective: CC: I ve been recovering from a cold, but the cough is getting worse even though my nose is not running anymore. Sometimes the cough is so bad that it keeps me awake at night. HPI: MF recovered from a cold 1 month ago, but still suffers from a cough with sputum. Patient has had a chronic cough since she quit smoking 5 years ago, but lately it is getting worse. Cough worsens with exercise and during the winter months. PMH: Tobacco dependence for 35 years, smoke-free for 5 years, HTN, Seasonal allergies 66 yo woman visits PCP for a lingering cough after having a cold 66 yo woman visits PCP for a lingering cough after having a cold Objective: Medications: Amlodipine 10mg PO QAM HCTZ 25 mg PO QAM Nasonex 2 sprays in each nostril QD during allergy season Claritin D PO QD during allergy season PE: General- Overweight female coughing with clear sputum. VS: BP138/85, P 110, RR 22, Wt 70kg, Ht 5 4, T 37 degrees, O2 sat 90% Diagnosis: CXR - Normal Spirometry - FEV1 = 0.65, FEV1/FVC= 76% (Referral to pulmonologist) Assessment: 1) Undiagnosed Stage II moderate COPD - uncontrolled 2) HTN - controlled 3) Seasonal allergic rhinitis - controlled

Page 11 Stage II moderate COPD - uncontrolled Conclusion Plan: Educate patient about disease and disease progression Pharmacologic regimen: Start short-acting beta-agonist inhaler PRN and tioptropium inhalation QD Education patient on inhaler technique Re-evaluate in 1 month Schedule for influenza (seasonal) and pneumococcal vaccinations Improve diagnosis of COPD in women (increased suspicion, spirometry, referral to specialist) Education: Prevention Smoking Women at higher risk Management: Smoking cessation (with increased attention to preventing relapse) Vaccines Pharmacotherapy Use therapies based on severity of COPD Notes Notes