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COPD Chronic Obstructive Pulmonary Disease

COPD Chronic Obstructive Pulmonary Disease. Charlene E. McEvoy, MD, MPH HealthPartners Lung and Sleep Health Clinic HealthPartners Research Foundation Assistant Professor of Medicine, University of Minnesota. COPD: Objectives. Definition and Overview Diagnosis and Assessment

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COPD Chronic Obstructive Pulmonary Disease

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  1. COPD Chronic Obstructive Pulmonary Disease Charlene E. McEvoy, MD, MPH HealthPartners Lung and Sleep Health Clinic HealthPartners Research Foundation Assistant Professor of Medicine, University of Minnesota

  2. COPD: Objectives • Definition and Overview • Diagnosis and Assessment • Therapeutic Options • Manage Stable COPD • Manage Exacerbations • Manage Comorbidities

  3. COPD: What is it? • COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. • Exacerbations and comorbidities contribute to the overall severity in individual patients.

  4. Burden of COPD • Increasing Global Prevalence • 4th-leading cause of death worldwide • 12th-leading cause of disability • By 2020: 3rd-leading cause of death, 5th-leading cause of disability • Annual cost: $40 billion Murray CJL, Lopez AD. Global burden of disease…1990-projected to 2020; Harvard University Press, 1996

  5. Burden of COPD • COPD is a major public health problem in USA • 5% of adult population (1 in 20 adults) • 16 to 20 million cases • 4th leading cause of death: 112,000 deaths annually • 2nd leading cause of disability • In 2002 more women in US died of COPD then men • Michaud CM, et al. JAMA. 2002; 285: 535-39 • Sullivan SD, et al. Chest. 2000; 117(2 suppl): 5s-9s..

  6. Burden of COPD • Widely under-diagnosed • National Health and Nutrition Examination Survey (NHANES III) 13.5 million men, and 10.5 million women have mild or moderate COPD • 37% with COPD not diagnosed

  7. Burden of COPD • Hospitalizations account for more than one half of all COPD-related medical costs • In 2010 there were 669,000 hospitalizations for COPD in the United States with a mean length of stay of 4.5 days • Mean cost of the index hospitalization for COPD was $7,100 and for the COPD readmission was $8,400. • Sullivan SD, Ramsey SD, Lee TA. Chest. 2000;117:5S-9S. Hilleman DE, Dewan N, Malesker M, Friedman M. Chest. 2000;118:1278-85. http://hcupnet.ahrq.gov/. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb121.pdf

  8. Burden of COPD • Hospitalizations for COPD exacerbations are highly morbid events that are associated with impairment of health-related quality of life, permanent loss of lung function, and decreased life expectancy(1-3) • A large sampling of hospital discharges in the United States  showed that 30-day readmission rates  for index COPD hospitalizations in 2008 were 7.1% for a primary diagnosis of COPD and 20.5% for any diagnosis • Within the VA medical system, one-year COPD readmission rates and all cause mortality are 25% and 21%, respectively (8). • At Regions Hospital Jan 1 2007 to Dec 31, 2009 – 1 year COPD readmission rate and all cause mortality were 21% and 15%, respectively 1. Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Am J Respir Crit Care Med. 1998;157:1418-22. 2. Kanner RE, Anthonisen NR, Connett JE; Lung Health Study Research Group. Am J Respir Crit Care Med. 2001;164:358-64. 3. Soler-Cataluna JJ, Mart’nez-Garc’a MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Thorax. 2005;60:925-31.

  9. COPD: Diagnosis • Definition and Overview • Diagnosis and Assessment • Therapeutic Options • Manage Stable COPD • Manage Exacerbations • Manage Comorbidities

  10. COPD: Risk Factors • Genes • Exposure to particles • Tobacco smoke • Occupational dusts, organic and inorganic • Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings • Outdoor air pollution Lung growth and development Gender Age Respiratory infections Socioeconomic status Asthma/Bronchial hyperreactivity Chronic Bronchitis

  11. Risk Factors for COPD Genes Infections Socio-economic status Aging Populations

  12. COPD: Diagnosis • A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease. • Spirometry is required to make the diagnosis; the presence of a post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation and thus of COPD.

  13. Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS shortness of breath tobacco chronic cough occupation sputum indoor/outdoor pollution SPIROMETRY: Required to establish diagnosis

  14. Flow Volume Loops COPD Normal Predicted Actual 8 7 6 5 4 3 2 1 0 -2 -3 -4 -5 8 6 4 2 0 -2 -4 -6 1 sec 1 sec Flow (L/s) Flow (L/s) TLC RV IC IC 6 5 4 3 2 8 7 6 5 4 3 2 Volume (L) Volume (L)

  15. Differential Diagnosis • Asthma • CHF • Bronchiectasis • Tuberculosis • Obliterative bronchiolitis • onset younger age, nonsmokers, h/o RA or fume exposure • Diffuse panbronchiolitis • Male nonsmokers, chronic sinusitis, centrilobular nodular opacities and hyperinflation

  16. Assessment of COPD: Goals • Determine the severity of the disease, its impact on the patient’s health status and the risk of future events (for example exacerbations)to guide therapy. Consider the following aspects of the disease separately: • current level of patient’s symptoms • severity of the spirometric abnormality • frequency of exacerbations • presence of comorbidities.

  17. Global Strategy for Diagnosis, Management and Prevention of COPDAssessment of Symptoms COPD Assessment Test (CAT):An 8-item measure of health status impairment in COPD (http://catestonline.org). Breathlessness Measurement using the Modified British Medical Research Council (mMRC) Questionnaire:relates well to other measures of health statusand predicts future mortality risk.

  18. Global Strategy for Diagnosis, Management and Prevention of COPDModified MRC (mMRC)Questionnaire

  19. Global Strategy for Diagnosis, Management and Prevention of COPDClassification of Severity of Airflow Limitation in COPD* In patients with FEV1/FVC < 0.70: GOLD 1: MildFEV1> 80% predicted GOLD 2: Moderate50% < FEV1 < 80% predicted GOLD 3: Severe30% < FEV1 < 50% predicted GOLD 4: Very SevereFEV1 < 30% predicted *Based on Post-Bronchodilator FEV1

  20. Assessment of COPD • Assess symptoms • Assess degree of airflow limitation using spirometry • Assess risk of exacerbations Usehistory of exacerbations and spirometry. Twoexacerbations or more within the last year or an FEV1 < 50 % of predictedvalueare indicators of highrisk

  21. Combined Assessment of COPD • Assess symptoms • Assess degree of airflow limitation using spirometry • Assess risk of exacerbations Combine these assessments for the purpose of improving management of COPD

  22. Combined Assessment of COPD Use combined assessment Patient is now in one of four categories: A: Les symptoms, low risk B: More symtoms, low risk C: Less symptoms, high risk D: More Symtoms, high risk 4 (C) (D) > 2 3 Risk (GOLD Classification of Airflow Limitation) Risk (Exacerbation history) 2 1 (A) (B) 0 1 mMRC 0-1 CAT < 10 mMRC > 2 CAT >10 Symptoms (mMRC or CAT score))

  23. Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history

  24. Assess COPD Comorbidities COPD patients are at increased risk for: • Cardiovascular diseases • Osteoporosis • Respiratory infections • Anxiety and Depression • Diabetes • Lung cancer • These comorbid conditions may influence mortality and hospitalizations and should be looked for routinely, and treated appropriately.

  25. Additional Investigations Chest X-ray: Seldom diagnostic but valuable to exclude alternative diagnoses and establish presence of significant comorbidities.  Lung Volumes and Diffusing Capacity:Help to characterize severity, but not essential to patient management.  Oximetry and Arterial Blood Gases:Pulse oximetry can be used to evaluate a patient’s oxygen saturation and need for supplemental oxygen therapy. Alpha-1 Antitrypsin Deficiency Screening: Perform when COPD develops in patients of Caucasian descent under 45 years or with a strong family history of COPD.

  26. Global Strategy for Diagnosis, Management and Prevention of COPDAdditional Investigations Exercise Testing: Objectively measured exercise impairment, assessed by a reduction in self-paced walking distance (such as the 6 min walking test) or during incremental exercise testing in a laboratory, is a powerful indicator of health status impairment and predictor of prognosis. Composite Scores: Several variables (FEV1, exercise tolerance assessed by walking distance or peak oxygen consumption, weight loss and reduction in the arterial oxygen tension) identify patients at increased risk for mortality.

  27. COPD: Treatment • Definition and Overview • Diagnosis and Assessment • Therapeutic Options • Manage Stable COPD • Manage Exacerbations • Manage Comorbidities

  28. Therapeutic Options: Key Points • Smoking cessation has the greatest capacity to influence the natural history of COPD. • Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates. • All COPD patients benefit from regular physical activity and should repeatedly be encouraged to remain active.

  29. Therapeutic Options: Key Points • Appropriate pharmacologic therapy can reduce COPD symptoms, reduce the frequency and severity of exacerbations, and improve health status and exercise tolerance. • None of the existing medications for COPD has been shown conclusively to modify the long-term decline in lung function. • Influenza and pneumococcal vaccination should be offered depending on local guidelines.

  30. FEV 1 (liters) Natural History of COPD 4 3 Nonsmoker Average smoker 2 Symptoms 1 “Susceptible” smoker Death 0 25 35 45 55 65 Age (years)

  31. Prevention of COPD Progression Smoking Cessation Sustained quitters 2.9 2.8 2.7 Mean FEV1 (L) 2.6 Continuing smokers 2.5 2.4 0 1 2 3 4 5 Years of follow-up Anthionsen, et al. JAMA 1994;272:1497

  32. Prevention of COPD Progression:Smoking Cessation • Only therapy proven to slow the decline in lung function • Reduces all cause mortality by 27% • Difficult to achieve • long-term abstinence rates can be as high as 25% in patients with early COPD Anthonisen NR, Ann Intern Med. 2005;142:233-239.

  33. Smoking Cessation • Single MD recommendation 5% sustained quit rate • WHO: 75 to 80% of smokers want to quit • Strong direct relationship between the intensity of counseling and results

  34. Smoking Cessation:THE 5A Strategy • Ask • All patients asked at every visit smoking status • Advice • Strongly urge every smoker to quit • Assess • Ask if willing to attempt quitting in next 30 days • Assist • Help patient with quit plan • Arrange • Schedule follow-up visit or phone contact

  35. Smoking Cessation • Nicotine replacement therapy & counseling • 25% sustained quit rate • Bupropion (Zyban™) & counseling • 25 to 29% sustained quit rate • Varenicline (Chantix) & counseling • 43% sustained quit rate

  36. Therapeutic Options: Risk Reduction • Encourage comprehensive tobacco-control policies with clear, consistent, and repeated nonsmoking messages. • Emphasize primary prevention, best achieved by elimination or reduction of exposures in the workplace. Secondary prevention, achieved through surveillance and early detection, is also important. • Reduce or avoid indoor air pollution from biomass fuel, burned for cooking and heating in poorly ventilated dwellings. • Advise patients to monitor public announcements of air quality and, depending on the severity of their disease, avoid vigorous exercise outdoors or stay indoors during pollution episodes.

  37. Therapeutic Options: COPD Medications

  38. Therapeutic Options: Bronchodilators • Bronchodilator medications are central to the symptomatic management of COPD. • Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. • The principal bronchodilator treatments are beta2- agonists, anticholinergics, theophylline or combination therapy. • The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects.

  39. Therapeutic Options: Bronchodilators • Long-acting inhaled bronchodilators are convenient and more effective for symptom relief than short-acting bronchodilators. • Long-acting inhaled bronchodilators reduce exacerbations and related hospitalizations and improve symptoms and health status. • Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator. • Cognitive function and ability to properly use inhaler therapy should be assessed regularly

  40. Prevention of Exacerbations Long-acting Inhaled Beta Agonists Favors LABA Favors Placebo Mahler 2002 Brusasco Calverley 1 Celli Chapman Rennard Van Noord Mahler 1999 Boyd Subtotal Salmeterol 0.81 (0.73 - 0.90) Calverley 2 Aalbers Rossi Wadbo Dahl Szafranski Subtotal Formoterol 0.84 (0.74 - 0.97) 0.82 (0.76 - 0.90) Total 0.2 0.5 1 2 5 Relative Risk (95% CI) of Exacerbation Wilt T, Niewoehner DE, Kim C, et al. AHRQ Report 05-E017-2, 2005

  41. Hospitalizations for COPDEffect of Long Acting Anticholinergic Favors tiotropium Favors comparator Tiotropium vs placebo Brusasco 2003 Casaburi 2002 Niewoehner 2005 Subtotal Tiotropium vs ipratropium Vincken 2002 Subtotal Tiotropium vs salmeterol Brusasco 2003 Subtotal 0.65 ( 0.50, 0.85 ) 0.59 ( 0.32, 1.09 ) 0.59 ( 0.29, 1.23 ) 0.1 0.2 0.5 1 2 5 10 Odds ratio (95% CI) Barr RG, et al. The Cochrane Database of Systematic Reviews 2005, Issue 2.

  42. Therapeutic Options: Inhaled Corticosteroids • Regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted. • Inhaled corticosteroid therapy is associated with an increased risk of pneumonia. • Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients.

  43. Prevention of Exacerbations Inhaled Corticosteroids Favors ICS Favors Placebo Burge Calverley 03 Mahler 02 van der Valk Paggiaro Subtotal Fluticasone 0.81 (0.68 - 0.95) Bourbeau Calverly 04 Szafranski Vestbo Subtotal Budesonide 0.78 (0.66 - 0.91) Weir Subtotal Beclomethasone 0.64 (0.41 - 1.00) Total 0.78 (0.70 - 0.88) 0.2 0.5 1 2 5 Relative Risk (95% CI) of Exacerbation Wilt T, Niewoehner DE, Kim C, et al. AHRQ Report 05-E017-2, 2005

  44. Therapeutic Options: Systemic Corticosteroids • Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio. • Unless there is co-morbid asthma

  45. Therapeutic Options: Combination Therapy • An inhaled corticosteroid combined with a long-acting beta2-agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD. • Combination therapy is associated with an increased risk of pneumonia. • Addition of a long-acting beta2-agonist/inhaled glucocorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits.

  46. Therapeutic Options: Phosphodiesterase-4 Inhibitors • In patients with severe and very severe COPD (GOLD 3 and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor (PDE-4), roflumilast, reduces exacerbations treated with oral glucocorticosteroids.

  47. Therapeutic Options: Macrolide Antibiotics • Adding azithromycin (250 mg/day) x 1 year to usual Rx of patients with an  risk of COPD exacerbations •  the frequency of AECOPDs •  Improves QOL •  Causes hearing  in a small fraction of patients • Provisos •  HR < 100, no apparent risk of QTc prolongation •  Hearing  95th percentile for age • Effect of Rx on macrolide resistance in • community bacterial flora unknown

  48. Azithro Placebo Time to First AECOPD P < 0.001 Log-rank 1.00 0.80 Median = 266 days 0.60 Proportion Free of AECOPD (%) 0.40 Median = 174 days 0.20 HR = 0.73 (95% CI 0.63, 0.84), P < 0.0001 0 45 90 135 180 225 270 315 360 Time (days)

  49. Therapeutic Options: Other Pharmacologic Treatments • Influenza vaccines can reduce serious illness. • Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted. • .

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