1. COPD is a chronic inflammatory lung disease characterized by airflow limitation that is usually caused by long-term exposure to irritating gases or particulate matter, most commonly from cigarette smoking. 2. Diagnosis of COPD involves clinical evaluation of symptoms and medical history combined with lung function tests, particularly spirometry. 3. Current guidelines classify COPD severity into four stages based on lung function measurements and symptoms, and recommend treatments that include bronchodilators, corticosteroids, and supplemental oxygen for advanced disease.

1. Lecture 2

2. Learning objectives – 1 To understand that COPD is: a disease state of airflow limitation that is not fully reversible a chronic inflammatory condition often caused by chronic bronchitis, emphysema or a mixture of both pathologically different from asthma usually the result of cigarette smoking or occupational exposure to small particles or dusts increasing in prevalence, particularly in women the cause of significant direct and indirect costs

3. Learning objectives – 2 To understand that COPD is: associated with symptoms such as chronic cough, chronic mucus production and breathlessness diagnosed by assessment of clinical signs and symptoms together with spirometric measurements of airflow obstruction To understand the importance of spirometry and the use of flow-volume loops in the diagnosis of COPD To understand current guidelines for the diagnosis and staging of COPD (GOLD)

4. Learning objectives – 3 To understand current guidelines for the treatment of COPD (GOLD) To understand the unique position of Foradil ® Aerolizer™ in the treatment of COPD

5. The common component of COPD is airflow obstruction Chronic bronchitis Emphysema Airflow obstruction Asthma

6. Summary of risk factors for the development of COPD Smoking and passive smoking Occupational factors Genetic factors, e.g. AAT deficiency Air pollution Atopy and hyperresponsive airways Infections

7. Clinical features of advanced COPD Cyanosis Distention of veins in neck Liver enlargement Cor pulmonale Anorexia and weight loss Hypoxaemia Hypercapnia

8. Diagnostic measures recommended by major Thoracic Societies Clinical and smoking history Symptoms (especially dyspnoea, cough, sputum and wheezing) Physical examination Pre- and post-bronchodilator spirometry Chest radiography (to exclude other diseases) ATS. Am J Respir Crit Care Med 1995 ERS. Eur Respir J 1995 BTS. Thorax 1997 Pauwels RA, et al. Am J Respir Crit Care Med 2001

9. GOLD guidelines outline key points in COPD diagnosis Chronic cough Present intermittently or every day Often present throughout the day; seldom only nocturnal Chronic sputum production Any pattern of chronic sputum production may indicate COPD Dyspnoea that is: Progressive (worsens over time) Persistent (present every day) Described by the patient as an ‘increased effort to breathe’, or ‘gasping’ Worse during exercise Worse during respiratory infections History of exposure to risk factors, especially: Tobacco smoke Occupational dusts and chemicals Smoke from home cooking and heating fuels Pauwels RA, et al. Am J Respir Crit Care Med 2001

10. GOLD guidelines: Classification of severity of COPD Stage Characteristics 0: At risk - Normal spirometry - Chronic symptoms (cough, sputum production) I: Mild COPD - FEV 1 /FVC <70% - FEV 1  80% predicted - With or without chronic symptoms (cough, sputum production) II: Moderate COPD - FEV 1 /FVC <70% - 30%  FEV 1 <80% predicted (IIA: 50%  FEV 1 <80% predicted, IIB: 30%  FEV 1 <50% predicted) - With or without chronic symptoms (cough, sputum production, dyspnoea) III: Severe COPD - FEV 1 /FVC <70% - FEV 1 <30% predicted or FEV 1 <50% predicted plus respiratory failure or clinical signs of right heart failure

11. What Is Asthma? Asthma is a chronic disease that affects the airways, which causes breathing problems. It can be life threatening. The inside walls of the airways are inflamed (swollen). The inflammation makes the airways very sensitive, and they tend to react strongly to allergens or irritants. When the airways react, they get narrower and less air flows through to the lung tissues. This causes symptoms like wheezing (a whistling sound when you breathe), coughing, chest tightness, and trouble breathing. Breathing problems are called attacks or episodes of asthma.

12. Epidemiology About 150 million people around the world suffer from asthma. Most common chronic illness of childhood: 10% of children and 5% of adults) / Prevalence is approximately 6% (3% in Japan). More boys than girls, but in adulthood, more women than men. Age: <15 (12.4 % ), 15-44 (37.9%), 45-64 (25.7%), >65 (23.0%) (At primary hospital, 46% of patients are < 15 years old). Annual death of c.a. 180,000 Annual incidence: 0.2% Ethnic difference: African-American twice higher than Caucasian. No info related to Asian versus Caucasian

13. Increase in Asthma Prevalence with Time 1982 1988 1992 1968 1982 1979 1984 1989 1975 1973 1971-74 1976-80 Source: Global Initiative for Asthma NHLBI/WHO Workshop Report 1996 *Diagnosed asthma: asthma diagnosed at any time. Asthma and/or wheeze.

14. Market Size CAGR: € + 14.7% USD + 6.2% SU - 0.2% annual growth rate % + 9.3 + 8.5 + 17.6 + 24.3 Asthma Worldwide: Value 1996 - 2000

15. Clinical Signs and Symptoms Common asthma symptoms are: Coughing. Coughing from asthma is often worse at night or early in the morning, making it hard to sleep. Wheezing. Wheezing is a whistling or squeaky sound when you breathe. Chest tightness. This can feel like something is squeezing or sitting on the chest. Shortness of breath. Some people say they can't catch their breath, or they feel breathless or out of breath. You may feel like you can't get enough air in or out of your lungs. Faster breathing or noisy breathing.

16. Pathophysiology Etiology is unknown as of today. However, the factors listed below may worsen asthma: Allergens Animal dander (from the skin, hair, or feathers of animals) Dust mites (contained in house dust) Cockroaches Pollen from trees and grass Mould (indoor and outdoor) Irritants Cigarette smoke Air pollution Cold air or changes in weather Strong odors from painting or cooking Scented products Strong emotional expression (including crying or laughing hard), and stress Others Medications such as aspirin and beta-blockers Sulfites in food (dried fruit) or beverages (wine) A condition called gastroesophageal reflux disease (GERD) that causes heartburn and can worsen asthma symptoms, especially at night. Irritants or allergens that you may be exposed to at your work such as special chemicals or dusts Infections.

17. Ethnic Differences Extrinsic factors: the incidence and prevalence of asthma vary from country to country and region to region. The exact reasons behind such differences are unknown but are presumed to be due to the differences in external factors (socioeconomic, types of environmental allergens, dietary, etc.) Intrinsic factors: no clear racial predisposition has been identified although some genetic linkages have been demonstrated. (Need assessment in disease prevalence, medical practice, drug metabolism, availability of medical technologies, laboratory test ordering practicing, drug prescribing practice, healthcare financing policy must be considered. )

18. Diagnosis and Classification MEDICAL HISTORY PHYSICAL EXAMINATION Hyper-expansion of the thorax, Sounds of wheezing during normal breathing, or a prolonged phase of forced exhalation Increased nasal secretion, mucosal swelling, and nasal polyps. Atopic dermatitis/eczema or any other manifestation of an allergic skin condition. PULMONARY FUNCTION TESTING (SPIROMETRY) Spirometry measurements (FEV1, FVC, FEV1/FVC). ( 肺活量計 )

19. Standard of Care National Institutes of Health National Asthma Education and Prevention Program divides the medication into two: Quick Relief medicines give rapid, short-term treatment and are taken when you have worsening asthma symptoms that can lead to asthma episodes or attacks. You will feel the effects of these medicines within minutes. An example is a short-acting inhaled bronchodilator. Long-term Control medicines are taken every day, usually over long periods of time, to control chronic symptoms and to prevent asthma episodes or attacks. You will feel the full effects of these medicines after taking them for a few weeks. People with persistent asthma need long-term control medicines. Examples are inhaled corticosteroids, long-acting beta agonists, leukotriene modifier, theophyline, Cromolyn, nedocromil

20. GINA Stepwise Treatment Guidelines for Adults Cromolyn Theophylline Inhaled CS low/high dose Short-act  2 Long-act  2 Mild Intermittent Mild Persistent Moderate Persistent Severe Persistent GINA: Global Initiative for Asthma, CS: Corticosteroids, LTA: Leukotriene antagonist LTA Reliever Controller Oral CS

21. Definition of Exacerbations Genentech Decrease in AM PEFR > 20% on 3 of 7 days prior to visit Decrease in FEV 1 > 20% Urgent or unscheduled visit for asthma symptoms Increase in ß-agonist use of >50 % for at least 2 consecutive days Abbott Increase in inhaler use by > 33% of the number of occasions of use Decrease in FEV 1 > 20% Decrease in AM PEFR > 25% from previous Merck Decrease in PM PEFR > 20 % AM PEFR < 180 L/min Increase in ß-agonist use < 70 % (or at least 2 puffs) Increase in baseline symptom score > 50 % Awake all night Asthma attack resulting in an unscheduled visit, ER or hospital, treatment with oral steroids

22. Death Rates Are Increasing, Especially in North America

23. Two landmark surveys in USA (1998; 2,509 patients, 512 doctors, 101 nurses, 113 pharmacists) and Europe (1999; 2,803 patients) sponsored by GW 9 % of asthma patients hospitalized overnight for asthma in the past year in the US (7% in EU) 23% of asthma patients ER visit in the past year in the US (10% in EU) 49% of children and 25% of adult patients missed school or work in the past 12 months in the US (25% in EU) 30% of asthma patients awoke with breathing problems at least once a week during the past four weeks in the US (30% in EU) Guidelines vs. Reality

24. Chest X-rays do not have a pivotal role in diagnosis of COPD Hyperinflated lungs severe COPD Normal X-ray mild COPD

25. Measurements of lung function PEF peak expiratory flow FEV 1 forced expiratory volume in one second FVC forced vital capacity IVC inspiratory vital capacity FEF* forced expiratory flow *Also known as maximum expiratory flow (MEF)

26. Subdivisions of the total capacity of the lungs Total lung capacity Full inspiration Full expiration Tidal volume Residual volume Maximum forced inspiration Maximum forced expiration FVC

27. Lung function tests are pivotal for assessment of COPD severity FEV 1 reduced FVC normal/reduced (depending on severity) FEV 1 /FVC reduced FEF reduced PEF reduced IVC reduced