Asthma and COPDAsthma and COPD

李世偉

署立桃園醫院胸腔內科

GINA 2006 GOLD 2006

• 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

Asthma 與 COPD 之定義

Definition of AsthmaDefinition 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

Definition of COPD

COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.

Its pulmonary component is characterized by airflow limitation that is not fully reversible.

The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.

Asthma Prevalence and Mortality

SourceSource: Masoli M et al. Allergy 2004: Masoli M et al. Allergy 2004

台北市學童氣喘病及氣喘症狀盛行率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

(%)

COPD Prevalence Study in Latin America

The prevalence of post-bronchodilator FEV1/FVC < 0.70 increases steeply with age in 5 Latin American Cities

Source: Menezes AM et al. Lancet 2005

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998

00

0.50.5

1.01.0

1.51.5

2.02.0

2.52.5

3.03.0

Proportion of 1965 Rate Proportion of 1965 Rate

1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998 1965 - 19981965 - 1998

–59%–59% –64%–64% –35%–35% +163%+163% –7%–7%

CoronaryHeart

Disease

CoronaryHeart

Disease

StrokeStroke Other CVDOther CVD COPDCOPD All OtherCauses

All OtherCauses

Source: NHLBI/NIH/DHHSSource: NHLBI/NIH/DHHS

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

Factors that Exacerbate AsthmaFactors that Exacerbate Asthma

Allergens Respiratory infections Exercise and hyperventilation Weather changes Sulfur dioxide Food, additives, drugs

Mechanisms Underlying the Mechanisms Underlying the Definition of AsthmaDefinition of AsthmaMechanisms Underlying the Mechanisms Underlying the Definition of AsthmaDefinition of Asthma

Risk FactorsRisk Factors(for development of asthma)(for development of asthma)

Risk FactorsRisk Factors(for development of asthma)(for development of asthma)

INFLAMMATIONINFLAMMATIONINFLAMMATIONINFLAMMATION

AirwayAirway

HyperresponsivenessHyperresponsiveness

AirwayAirway

HyperresponsivenessHyperresponsiveness Airflow ObstructionAirflow ObstructionAirflow ObstructionAirflow Obstruction

Risk FactorsRisk Factors(for exacerbations)(for exacerbations) Risk FactorsRisk Factors(for exacerbations)(for exacerbations)

SymptomsSymptomsSymptomsSymptoms

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

Risk Factors for COPD

NutritionNutrition

InfectionsInfections

Socio-economic Socio-economic statusstatus

Aging PopulationsAging Populations

Source: Peter J. Barnes, MDSource: Peter J. Barnes, MD

Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MDSource: Peter J. Barnes, MD

Mechanisms: Asthma Inflammation

Cellular Mechanisms of COPDCellular Mechanisms of COPD

AsthmaAsthmaSensitizing agent

COPDCOPDNoxious agent

Asthmatic airway inflammationAsthmatic airway inflammationCD4+ T-lymphocytesCD4+ T-lymphocytes

EosinophilsEosinophils

COPD airway inflammationCOPD airway inflammationCD8+ T-lymphocytesCD8+ T-lymphocytes

MacrophagesMacrophagesNeutrophilsNeutrophils

Airflow limitationAirflow limitationCompletelyreversible

Completelyirreversible

Small airway diseaseAirway inflammationAirway remodeling

Parenchymal destructionLoss of alveolar attachments

Decrease of elastic recoil

Inflammation and remodeling in asthmatic airway

• Inflammation (I)• Mucus Plugging (MP)• Subepithelial Fibrosis (SF)• Myocyte Hypertrophy And Hyperplasia (MH)• Neovascularization (N)

Asthma COPD

Epithelial loss Thickened RBM

Epithelial metaplasiaNormal RBM

Asthma Asthma 與 與 COPD COPD 之診斷之診斷

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

FEVFEV11 PEFR PEFR

Typical Spirometric (FEV1) TracingsTypical Spirometric (FEV1) Tracings

11Time (sec)Time (sec)

22 33 44 55

FEV1FEV1

VolumeVolume

Normal SubjectNormal Subject

Asthmatic (After Bronchodilator)Asthmatic (After Bronchodilator)

Asthmatic (Before Bronchodilator)Asthmatic (Before Bronchodilator)

Note: Each FEV1 curve represents the highest of three repeat measurements

Daily Variability of PEFRDaily Variability of PEFR

PEFR at night – PEFR at morning

--------------------------------------------------------- x 100%

½ (PEFR at night + PEFR at morning)

Measuring Variability of Peak Expiratory Flow

Monitoring of asthma treatmentMonitoring of asthma treatment

ZonePEF

(% of best)Daily variability

of PEF

Green > 80% < 20%

Yellow 60-80% 20-30%

Red <60% >30%

Measuring Airway Responsiveness

SYMPTOMScoughcough

sputumsputumshortness of breathshortness of breath

EXPOSURE TO RISKFACTORS

tobaccotobaccooccupationoccupation

indoor/outdoor pollutionindoor/outdoor pollution

SPIROMETRYSPIROMETRY

Diagnosis of COPDDiagnosis of COPD

Spirometry: Normal and Patients with COPD

Differential Diagnosis: Differential Diagnosis: COPD and AsthmaCOPD 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

Asthma Asthma 與 與 COPD COPD 之治療之治療Asthma Asthma 與 與 COPD COPD 之治療之治療

1997 NAEPP Guidelines1997 NAEPP Guidelines Classification of Asthma Severity Classification of Asthma Severity

34

21

Severe Persistent

Moderate Persistent

Mild Persistent

Mild Intermittent

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。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

Levels of Asthma Control

Characteristic Controlled Partly controlled(Any present in any week)

Uncontrolled

Daytime symptomsNone (2 or less / week)

More than twice / week

3 or more features of partly controlled asthma present in any week

Limitations of activities

None Any

Nocturnal symptoms / awakening

None Any

Need for rescue / “reliever” treatment

None (2 or less / week)

More than twice / week

Lung function (PEF or FEV1)

Normal< 80% predicted or

personal best (if known) on any day

Exacerbation None One or more / year 1 in any week

Component 4: Asthma Management and Prevention Program

Controller MedicationsComponent 4: Asthma Management and Prevention Program

Controller Medications

Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β2-agonists Anti-IgE Systemic glucocorticosteroids

Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β2-agonists Anti-IgE Systemic glucocorticosteroids

Component 4: Asthma Management and Prevention Program

Reliever MedicationsComponent 4: Asthma Management and Prevention Program

Reliever Medications

Rapid-acting inhaled β2-agonists

Systemic glucocorticosteroids

Anticholinergics

Theophylline

Short-acting oral β2-agonists

Rapid-acting inhaled β2-agonists

Systemic glucocorticosteroids

Anticholinergics

Theophylline

Short-acting oral β2-agonists

controlled

partly controlled

uncontrolled

exacerbation

LEVEL OF CONTROLLEVEL OF CONTROL

maintain and find lowest controlling step

consider stepping up to gain control

step up until controlled

treat as exacerbation

TREATMENT OF ACTIONTREATMENT OF ACTION

TREATMENT STEPSREDUCE INCREASE

STEP

1STEP

2STEP

3STEP

4STEP

5

RE

DU

CE

INC

RE

AS

E

Step 1 – As-needed reliever medication

Patients with occasional daytime symptoms of short duration

A rapid-acting inhaled β2-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

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

Step 3 – Reliever medication plus one or two controllers

For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled long-acting β2-agonist either in a combination inhaler device or as separate components (Evidence A)

Inhaled long-acting β2-agonist must not be used as monotherapy

For children, increase to a medium-dose inhaled glucocorticosteroid (Evidence A)

Treating to Achieve Asthma Control

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

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

Step 4 – Reliever medication plus two or more controllers

Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-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 β2-agonist (Evidence B)

Treating to Achieve Asthma Control

Treating to Achieve Asthma Control

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)

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

Severity of COPD (GOLD July 2003)Severity of COPD (GOLD July 2003)Stage Characteristics

0: At Risk normal spirometry, chronic symptoms (cough, sputum production)

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

IV: Very Severe III: Severe II: Moderate I: Mild

Therapy at Each Stage of COPD

FEV1/FVC < 70%

FEV1 > 80% predicted

FEV1/FVC < 70%

50% < FEV1 < 80% predicted

FEV1/FVC < 70%

30% < FEV1 < 50% predicted

FEV1/FVC < 70%

FEV1 < 30% predicted

or FEV1 < 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 vaccinationAdd short-acting bronchodilator (when needed)

Add long term oxygen if chronic respiratory failure. Consider surgical treatments

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

THANKS FOR YOUR ATTENTIONTHANKS FOR YOUR ATTENTION