1. Asthma and COPD 李世偉 署立桃園醫院胸腔內科

2. GINA 2006 GOLD 2006

3. Definition and Overview Diagnosis and Classification Asthma Medications Asthma Management and Prevention Program Implementation of Asthma Guidelines in Health Systems Definition and Overview Diagnosis and Classification Asthma Medications Asthma Management and Prevention Program Implementation of Asthma Guidelines in Health Systems Definition, Classification Burden of COPD Risk Factors Pathogenesis, Pathology, Pathophysiology Management Practical Considerations Definition, Classification Burden of COPD Risk Factors Pathogenesis, Pathology, Pathophysiology Management Practical Considerations GINA 2006 GOLD 2006

4. Asthma 與 COPD 之定義

5. Definition of Asthma A chronic inflammatory disorder of the airways Many cells and cellular elements play a role Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing Widespread, variable, and often reversible airflow limitation A chronic inflammatory disorder of the airways Many cells and cellular elements play a role Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing Widespread, variable, and often reversible airflow limitation

6. Definition of COPD n COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. n Its pulmonary component is characterized by airflow limitation that is not fully reversible. n The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.

7. Asthma Prevalence and Mortality Source: Masoli M et al. Allergy 2004

8. 台北市學童氣喘病及氣喘症狀盛行率 1974 年 1985 年 1991 年 1994 年 2001 年 (%)

9. COPD Prevalence Study in Latin America The prevalence of post-bronchodilator FEV 1 /FVC < 0.70 increases steeply with age in 5 Latin American Cities Source: Menezes AM et al. Lancet 2005

10. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 0 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 1998 –59% –64% –35% +163% –7% Coronary Heart Disease Coronary Heart Disease Stroke Other CVD COPD All Other Causes All Other Causes Source: NHLBI/NIH/DHHS

11. Risk Factors for Asthma Host factors: predispose individuals to, or protect them from, developing asthma Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist Host factors: predispose individuals to, or protect them from, developing asthma Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist

12. Factors that Exacerbate Asthma Allergens Respiratory infections Exercise and hyperventilation Weather changes Sulfur dioxide Food, additives, drugs

13. Mechanisms Underlying the Definition of Asthma Risk Factors (for development of asthma) Risk Factors (for development of asthma) INFLAMMATIONINFLAMMATION AirwayHyperresponsivenessAirwayHyperresponsiveness Airflow Obstruction Risk Factors Risk Factors (for exacerbations) Risk Factors Risk Factors (for exacerbations) SymptomsSymptoms

14. Risk Factors for COPD Lung growth and development Oxidative stress Gender Age Respiratory infections Socioeconomic status Nutrition Comorbidities 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

15. Risk Factors for COPD Nutrition Infections Socio-economic status Aging Populations

16. Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators

17. Source: Peter J. Barnes, MD Mechanisms: Asthma Inflammation

18. Cellular Mechanisms of COPD

20. Asthma Sensitizing agentCOPD Noxious agent Asthmatic airway inflammation CD4+ T-lymphocytes Eosinophils COPD airway inflammation CD8+ T-lymphocytes MacrophagesNeutrophils Airflow limitation Completely reversible Completely irreversible Small airway disease Airway inflammation Airway remodeling Parenchymal destruction Loss of alveolar attachments Decrease of elastic recoil

21. Inflammation and remodeling in asthmatic airway Inflammation (I) Mucus Plugging (MP) Subepithelial Fibrosis (SF) Myocyte Hypertrophy And Hyperplasia (MH) Neovascularization (N)

25. Asthma COPD Epithelial loss Thickened RBM Epithelial metaplasia Normal RBM

26. Asthma 與 COPD 之診斷

27. Asthma Diagnosis History and patterns of symptoms Measurements of lung function - Spirometry - Peak expiratory flow Measurement of airway responsiveness Measurements of allergic status to identify risk factors Extra measures may be required to diagnose asthma in children 5 years and younger and the elderly History and patterns of symptoms Measurements of lung function - Spirometry - Peak expiratory flow Measurement of airway responsiveness Measurements of allergic status to identify risk factors Extra measures may be required to diagnose asthma in children 5 years and younger and the elderly

28. FEV 1 PEFR FEV 1 PEFR

29. Typical Spirometric (FEV 1 ) Tracings 1 Time (sec) 2345 FEV 1 Volume Normal Subject Asthmatic (After Bronchodilator) Asthmatic (Before Bronchodilator) Note: Each FEV 1 curve represents the highest of three repeat measurements

30. Daily Variability of PEFR PEFR at night – PEFR at morning --------------------------------------------------------- x 100% ½ (PEFR at night + PEFR at morning)

31. Measuring Variability of Peak Expiratory Flow

32. Monitoring of asthma treatment Zone PEF (% of best) Daily variability of PEF Green> 80%< 20% Yellow60-80%20-30% Red<60%>30%

33. Measuring Airway Responsiveness

34. SYMPTOMS cough sputum shortness of breath EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution SPIROMETRY Diagnosis of COPD è è è è è è

35. Spirometry: Normal and Patients with COPD

36. Differential Diagnosis: COPD and Asthma COPD ASTHMA Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation Onset early in life (often childhood) Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, and/or eczema also present Family history of asthma Largely reversible airflow limitation

37. Asthma 與 COPD 之治療

38. 1997 NAEPP Guidelines Classification of Asthma Severity 3 4 2 1 Severe Persistent Moderate Persistent Mild Persistent Mild Intermittent

39. 氣喘病的嚴重度分級標準 治療前之臨床症狀 日間症狀 夜間症狀 尖峰呼氣流速 4. 嚴重持續性 3. 中度持續性 2. 輕度持續性 1. 輕度間歇性 日常活動受限 每天都有, 每天都用乙二 型交感興奮吸入劑 每週都有，但少於 每天一次 少於每週一次, 氣 喘發作之間無症狀 經常性 大於每週一次 大於每月二次 每月二次或 二次以下 低於預測值的 60% 變異度大於 30% 介預測值的 60-80%, 變異度大於 30% 大於預測值的 80%, 變異度介於 20-30% 大於預測值的 80%, 變異度小 於 20% 只要符合症狀或尖峰呼氣流速值標準之一即可列入嚴重度分類，不必同時符合。 GINA 2002

40. Levels of Asthma Control CharacteristicControlled Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week 3 or more features of partly controlled asthma present in any week Limitations of activities NoneAny Nocturnal symptoms / awakening NoneAny Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day ExacerbationNone One or more / year 1 in any week

41. Component 4: Asthma Management and Prevention Program Controller Medications Component 4: Asthma Management and Prevention Program Controller Medications Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β 2 -agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β 2 -agonists Anti-IgE Systemic glucocorticosteroids Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β 2 -agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β 2 -agonists Anti-IgE Systemic glucocorticosteroids

42. Component 4: Asthma Management and Prevention Program Reliever Medications Component 4: Asthma Management and Prevention Program Reliever Medications  Rapid-acting inhaled β 2 -agonists  Systemic glucocorticosteroids  Anticholinergics  Theophylline  Short-acting oral β 2 -agonists  Rapid-acting inhaled β 2 -agonists  Systemic glucocorticosteroids  Anticholinergics  Theophylline  Short-acting oral β 2 -agonists

43. controlled partly controlled uncontrolled exacerbation LEVEL OF CONTROL maintain and find lowest controlling step consider stepping up to gain control step up until controlled treat as exacerbation TREATMENT OF ACTION TREATMENT STEPS REDUCEINCREASE STEP 1 STEP 2 STEP 3 STEP 4 STEP 5 REDUCE INCREASE

46. Step 1 – As-needed reliever medication  Patients with occasional daytime symptoms of short duration  A rapid-acting inhaled β 2 -agonist is the recommended reliever treatment (Evidence A)  When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment (step 2 or higher) Treating to Achieve Asthma Control

48. Step 2 – Reliever medication plus a single controller  A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A)  Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids Treating to Achieve Asthma Control

50. Step 3 – Reliever medication plus one or two controllers  For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled long-acting β 2 -agonist either in a combination inhaler device or as separate components (Evidence A)  Inhaled long-acting β 2 -agonist must not be used as monotherapy  For children, increase to a medium-dose inhaled glucocorticosteroid (Evidence A) Treating to Achieve Asthma Control

51. Additional Step 3 Options for Adolescents and Adults  Increase to medium-dose inhaled glucocorticosteroid (Evidence A)  Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)  Low-dose sustained-release theophylline (Evidence B) Treating to Achieve Asthma Control

53. Step 4 – Reliever medication plus two or more controllers  Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3  Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma Treating to Achieve Asthma Control

54. Step 4 – Reliever medication plus two or more controllers  Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist (Evidence A)  Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)  Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β 2 -agonist (Evidence B) Treating to Achieve Asthma Control

56. Step 5 – Reliever medication plus additional controller options  Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A)  Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A)

57. Treating to Maintain Asthma Control  When control as been achieved, ongoing monitoring is essential to: - maintain control - establish lowest step/dose treatment  Asthma control should be monitored by the health care professional and by the patient

58. Severity of COPD (GOLD July 2003) StageCharacteristics 0: At Risk normal spirometry, chronic symptoms (cough, sputum production) I: Mild COPD FEV 1 /FVC < 70% FEV 1  80% predicted II: Moderate COPD FEV 1 /FVC < 70% 50%  FEV1 < 80% predicted III: Severe COPD FEV 1 /FVC < 70% 30%  FEV1 < 50% predicted IV: Very Severe COPDFEV 1 /FVC < 70%, FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure

59. IV: Very Severe III: Severe II: Moderate I: Mild Therapy at Each Stage of COPD  FEV 1 /FVC < 70%  FEV 1 > 80% predicted  FEV 1 /FVC < 70%  50% < FEV 1 < 80% predicted  FEV 1 /FVC < 70%  30% < FEV 1 < 50% predicted  FEV 1 /FVC < 70%  FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add long term oxygen if chronic respiratory failure. Consider surgical treatments

60. Management of Stable COPD Other Pharmacologic Treatments  Antibiotics: Only used to treat infectious exacerbations of COPD  Antioxidant agents: No effect of n-acetylcysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids  Mucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD

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