Lecture 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

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)

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

The common component of COPDis airflow obstruction

Chronicbronchitis

Emphysema

Airflow obstruction

Asthma

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

Clinical features of advanced COPD

• Cyanosis• Distention of veins in neck• Liver enlargement• Cor pulmonale• Anorexia and weight loss• Hypoxaemia• Hypercapnia

ATS. Am J Respir Crit Care Med 1995ERS. Eur Respir J 1995 BTS. Thorax 1997Pauwels RA, et al. Am J Respir Crit Care Med 2001

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)

GOLD guidelines outline key points in COPD diagnosis

Chronic coughPresent intermittently or every dayOften present throughout the day; seldom only nocturnal

Chronic sputum productionAny 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 exerciseWorse during respiratory infections

History of exposure to risk factors, especially:Tobacco smokeOccupational dusts and chemicalsSmoke from home cooking and heating fuels

Pauwels RA, et al. Am J Respir Crit Care Med 2001

GOLD guidelines: Classification of severity of COPD

Stage Characteristics

0: At risk - Normal spirometry- Chronic symptoms (cough, sputum production)

I: Mild COPD - FEV1/FVC <70%- FEV1 80% predicted- With or without chronic symptoms (cough, sputum production)

II: Moderate COPD - FEV1/FVC <70%- 30% FEV1 <80% predicted (IIA: 50% FEV1 <80% predicted, IIB: 30% FEV1 <50% predicted)- With or without chronic symptoms (cough, sputum production, dyspnoea)

III: Severe COPD - FEV1/FVC <70%- FEV1 <30% predicted or FEV1 <50% predicted plus respiratory failure or clinical signs of right heart failure

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.

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

0

5

10

15

20

25

30

35

Australia New Zealand Wales USA France Tahiti

Dia

gn

ose

d a

sth

ma

* (%

)

1982 19881992 1968 1982 1979 198419891975 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.

Increase in Asthma Prevalence with Time

Market Size CAGR: € + 14.7% USD + 6.2% SU - 0.2%

0,000

0,500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000

5,500

1996 1997 1998 1999 2000

Eur

o m

illio

n

Others

Symptoms relievers

Symptoms controllers

Anti-inflammatory controllers

annual growth rate % + 9.3 + 8.5 + 17.6 + 24.3

Asthma Worldwide: Value 1996 - 2000

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.

PathophysiologyEtiology 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.

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. )

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 )

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

GINA Stepwise Treatment Guidelines for Adults

Cromolyn

Theophylline

LTA

Inhaled CSlow/high dose

Short-act 2

Long-act 2

Rel

ieve

rC

ontr

olle

r

Oral CS

MildIntermittent

Mild Persistent

ModeratePersistent

SeverePersistent

GINA: Global Initiative for Asthma, CS: Corticosteroids, LTA: Leukotriene antagonist

Definition of Exacerbations

Genentech• Decrease in AM PEFR > 20% on 3 of 7 days prior to visit• Decrease in FEV1 > 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 FEV1 > 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

Death Rates Are Increasing, Especially in North America

• 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

Chest X-rays do not have a pivotal role in diagnosis of COPD

Hyperinflated lungssevere COPD

Normal X-raymild COPD

Measurements of lung function

• PEF peak expiratory flow

• FEV1 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)

Subdivisions of the total capacity of the lungs

Totallung

capacity

Full inspiration

Full expiration

Tidal volume

Residual volume

Maximum forced inspiration

Maximum forced expiration

FVC

Lung function tests are pivotal for assessment of COPD severity

• FEV1 reduced

• FVC normal/reduced(depending on severity)

• FEV1/FVC reduced

• FEF reduced

• PEF reduced

• IVC reduced