2014/3/25

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簡榮彥 醫師

2014.3.29

Global Strategy for Diagnosis, Management and Prevention of COPD

COPD的定義

• 慢性阻塞性肺病（COPD）是可預防也可治療的疾病

• 其特徵為持續的呼氣氣流受阻（airflow

limitation）， 常具漸進性且伴有肺臟及呼吸道對有害微粒或氣體的慢性發炎反應。

• 急性惡化（exacerbation）與共病症（comorbidity）與疾病的整體嚴重度有關。

COPD Patients

Loss appetite, Malnutrition

Exertional Dyspnea

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SYMPTOMS EXPOSURE TO RISK

FACTORS

肺功能檢查

COPD 之診斷

è

咳嗽

氣促

黏痰

吸菸

職業

空氣污染

COPD 的危險因子

COPD 的產生導因於累積數十年的危險因子暴露，其盛行率通常與吸菸的盛行率直接相關

職業性或室內（如燃燒木材與生物燃料）所造成的空氣汙染也被證實是COPD 的危險因子

老化本身亦是COPD的危險因子之一，呼吸道及實質組織老化後的情形也與COPD 造成的結構改變十分相似

Risk Factors for COPD

Genes

Infections

Socio-economic

status

Aging Populations

診斷

FEV1 PEFR 肺功能檢查

Volu

me, lit

ers

Time, seconds

5

4

3

2

1

1 2 3 4 5 6

FEV1 = 1.8L

FVC = 3.2L

FEV1/FVC = 0.56

Normal

Obstructive

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COPD 之鑑別診斷 COPD嚴重度評估 (GOLD 2011)

評估症狀嚴重度

評估氣道阻塞程度

評估惡化(急性發作)的風險

評估共病症(comorbidities)

1. 修改過的英國醫學研究會問卷（the modified British Medical Research Council；mMRC） • 只評估呼吸困難造成的失能

2. COPD 評估測試（COPD Assessment Test；CAT)

• 廣泛涵蓋病人的日常生活及身心健康受疾病影響的程度。

症狀評估 mMRC問卷

評估氣道阻塞程度 - 肺功能

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評估急性發作的風險

高風險

過去一年發作兩次以上

肺功能 FEV1 < 50 % of predicted value

綜合性的COPD 評估

Patient Characteristic 肺功能 急性發作次數(過去一年)

mMRC CAT

A Low Risk

Less Symptoms GOLD 1-2 ≤ 1 0-1 < 10

B Low Risk

More Symptoms GOLD 1-2 ≤ 1 > 2 ≥ 10

C High Risk

Less Symptoms GOLD 3-4 > 2 0-1 < 10

D High Risk

More Symptoms GOLD 3-4 > 2 > 2

≥ 10

Global Strategy for Diagnosis, Management and Prevention of COPD

COPD嚴重度評估

When assessing risk, choose the highest risk

according to GOLD grade or exacerbation history

常見的COPD共病症(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.

Systemic

Inflammation

Target organs

Respiratory system

Systemic Effects of COPD

Nutritional abnormality and weight loss

Increasing resting energy expenditure

Abnormal body composition

Abnormal amino acid metabolism

Skeletal muscle dysfunction

Loss of muscle mass

Abnormal structure/function

Others

Cardiovascular effects

Nervous system effect

Skeletal effect

Bone marrow effects

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Causes of Deaths in COPD

Mannino et al. Thorax 2003

0% 20% 40% 60% 80% 100%

Severe COPD

Moderate COPD

Restricted lung

Normal Lung

COPD CVD Lung Ca Infection Other

0.0

0.5

1.0

1.5

2.0

2.5

109 % 96 % 88 % 80 % 63 %

FEV1

NHANES 1; N=1,861

RR

Relationship between COPD and CVD

27

Arterial Stiffness Is Independently Associated

With Emphysema Severity in Patients With

COPD

McAllister DA, et al. Am J Respir Crit Care Med. 2007;176:1208-1214. Permission requested.

r = 0.476

Incre

ased A

rteri

al S

tiffness

12.00

Pu

lse W

ave V

elo

city (

m/s

)

10.00

8.00

6.00

0.00 0.20 0.40 0.60

Worse Emphysema

Emphysema Severity (Pixel Index 910)

r = -0.243

Incre

ased A

rteri

al S

tiffness

12.00

Pu

lse W

ave V

elo

city (

m/s

)

10.00

8.00

6.00

25 50 75 100

FEV1 % Predicted

28

Systemic Inflammation Rises

With COPD Severity

CRP TNF-a

Severe

COPD

Moderate

COPD

Mild

COPD

Healthy

0

Serum C-Reactive Protein (mg/L)

20 30 40 50 60 70 10

Severe

COPD

Moderate

COPD

Mild

COPD

Healthy

0 40 100 60 80 20

Serum TNF-Alpha (pg/mL)

Reprinted from Pulm Pharmacol Ther, Vol 19, Franciosi LG, et al, Markers of disease severity in chronic

obstructive pulmonary disease, pp 189-199, Copyright 2006, with permission from Elsevier.

29

Airflow Obstruction and Osteoporosis in COPD

1.93.9

6.8

11

7.6

10.3

20.9

33

0

5

10

15

20

25

30

35

None Mild Moderate Severe

Perc

ent of

Subje

cts

with

Oste

oporo

sis

Severity of Airflow Obstruction

Men

Women

Sin DD, et al. Am J Med. 2003;114:10-14. 30

Increased Prevalence of Esophagitis,

Gastritis, or Gastric Ulcers in Patients With COPD

32

17

0

5

10

15

20

25

30

35

COPD Controls

Perc

ent

of

Patients

with G

astr

ic

Dis

ease

Mapel DW, et al. Chest. 2000;117:346-353.

*

*P<0.05 versus controls

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Many patients with COPD die from

causes other than COPD itself

1. Curkendall et al. Am J Respir Crit Care Med 2004. 2. Kiri et al. Am J Respir Crit Care Med 2004; 3. Rana et al. Diabetes Care 2004

4. Camilli et al. Am J Epidemiol 1991; 5. Hansell et al. Eur Respir J 2003.

COPD also puts patients at increased risk of

dying from other diseases

Patients with COPD are 2-5× more likely to die

from cardiovascular disease than those without

COPD1

COPD is also associated with reduced survival

in patients with lung cancer

The risk of type 2 diabetes is almost 2× for

women with COPD3

Many patients with COPD die from

causes other than COPD itself

Camilli et al. Am J Epidemiol 1991; Hansell et al. Eur Respir J 2003.

Where COPD is diagnosed, but is not the

underlying cause of death

25–55% of deaths are due to circulatory

diseases (e.g. heart disease and stroke)

4–11% of deaths are due to other respiratory

causes

7–15% of deaths are due to malignancies

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Systemic Inflammation and

Comorbidities

COPD

OSTEOPOROSIS DIABETES

BODY

COMPOSITION

INFLAMMATION

Agusti AG, et al. Eur Respir J. 2003;21:347-360.

Agusti A. Proc Am Thorac Soc. 2007;4:522-525.

CARDIOVASCULAR

DISEASE

GASTROINTESTINAL

DISORDER

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Assessing Comorbidities in COPD

Agusti A and Jardim J, personal communication.

Look for

Look for

COPD Comorbidities

If Smoker

穩定期患者之治療

1.支氣管擴張劑

2.類固醇

3.復健

4.氧氣治療

5.其他藥物:抗生素, 袪痰劑

6.外科手術: Bullectomy, LVRS, Transplantation

7.衛教

8.營養諮詢

減少危險因子暴露

Avoidance of noxious agents

smoking cessation

reduction of indoor pollution

reduction of occupational exposure

疫苗：

流感疫苗

肺炎球菌疫苗：在65歲以上COPD病人或不到65歲但FEV1 < 40%者建議接種。

(GOLD 2003)

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Exa

ce

rba

tio

ns p

er

ye

ar

> 2

1

0

mMRC 0-1

CAT < 10

GOLD 4

mMRC > 2

CAT > 10

GOLD 3

GOLD 2

GOLD 1

SAMA prn

or

SABA prn

LABA

or

LAMA

ICS + LABA

or

LAMA

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Pharmacologic Therapy

FIRST CHOICE

A B

D C

ICS + LABA

or

LAMA

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Pharmacologic Therapy (Medications in each box are mentioned in alphabetical order, and therefore not

necessarily in order of preference.)

Patient First choice Second choice Alternative Choices

A

SAMA prn

or

SABA prn

LAMA

or

LABA

or

SABA and SAMA

Theophylline

B

LAMA

or

LABA

LAMA and LABA SABA and/or SAMA

Theophylline

C

ICS + LABA

or

LAMA

LAMA and LABA

PDE4-inh.

SABA and/or SAMA

Theophylline

D

ICS + LABA

or

LAMA

ICS and LAMA or

ICS + LABA and LAMA or

ICS+LABA and PDE4-inh. or

LAMA and LABA or

LAMA and PDE4-inh.

Carbocysteine

SABA and/or SAMA

Theophylline

支氣管擴張劑

支氣管擴張劑是COPD症狀治療的主要

藥物。

常規使用長效型支氣管擴張劑較短效

型有效而方便

Nebulizer

Metered dose

inhaler

Dry powder inhaler

Devices for Aerosol Therapy

27%

9% 20%

12%

54% 80%

18% 10%

78%

66%

1%

2%

20% 1% 1% 1%

DPI MDI MDI/HC NEB

Exhaled

Apparatus

Oropharygeal

Lungs

Respirable Fr. in Different

Devices Metered dose inhaler (MDI)

體積小，易攜帶

經濟便宜

劑量穩定

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MDI 的缺點 效率差

傳統CFC推進劑造成臭氧層破壞(Ozone Depletion)

需良好技巧配合

冷媒效應

無計量器

需使用spacers

Ozone Depletion

HFA-134a

Spray plumes Speed

HFA-MDI

30 miles/hour

CFC-MDI

100 miles/hour

New

HFA-BDP CFC-BDP

Particle size and lung deposition

CFC vs. HFA

CFC HFA

MMAD

3.8 μm 1.2μm

Lung deposition 19.7 % 68.3 %

- peripheral 7.0 % 23.0 %

- intermediate 6.8 % 25.7 %

- central 5.9 % 19.6 %

(Jonathan Corren MD Clin Ther. 2003 Mar;25(3):776-98

Influence of temperature on MDI dose

CFC-Albuterol MDI

HFA Albuterol MDI

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Benefits from Novel HFA-MDIs

增加肺部藥物濃度（尤其是周邊small

airway)

衝力較小

減少冷媒效應

劑量更穩定

Dry power inhaler (DPI)

優點

呼吸啟動，不需複雜技巧

無推進劑、不會造成環境污染

體積小、方便隨身攜帶使用

不需spacer

包含計量計

Dry power inhaler 的缺點

需足夠吸氣能力，肺功能太差

之患者及小朋友 (< 5 歲) 不

適用

無法於呼吸衰竭及氣切患者使

用

Multi-dose易受潮，降低效果

較昂貴

肺部復健

COPD復建工作的目的主要有三：減少呼吸道症狀，提高病患生活品質，及增進日常之身心活動

肺部復健

肺部復健對COPD之助益 改善運動能力（A級證據力）。

減少呼吸短促之感覺（A級證據力）。

改善與健康相關的生活品質（A級證據力）。

減少住院次數及住院日數（A級證據力）。

減少COPD相關之焦慮及憂鬱（A級證據力）。

改善存活率（B級證據力）。

在訓練期間結束後優點仍可持續（B級證據力）。

心理支持是有助益（C級證據力）。

呼吸肌之訓練是有助益（C級證據力）。

腹式呼吸

噘嘴式呼吸

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早期治療 208

152

134

124

Scanlon PD et al: Lung Health Study AJRCCM 2000

MORE REVERSIBILITY EARLIER IN DISEASE

Mild COPD:

Reversibility

↓ inflammation 80

76

72

B/L 1 2 3 4 5

2682

2335

2059

1652

1818

Years in study

More severe COPD:

Less reversibility

No ↓ inflammation

FE

V1 (

% p

redic

ted)

Continuing smokers

p<0.001

55.6%

24% reduction

Placebo Tiotropium

p=0.06

42.4%

12% reduction

Placebo Tiotropium

Dusser et al. Eur Respir J 2006;27:547-555

MISTRAL: Proportion of patients

with ≥1 exacerbation

0

10

20

30

40

50

60

70

0

10

20

30

40

50

60

70

63.5%

FEV1 ≥ 50% FEV1 < 50%

56%

N=209 N=217 N=296 N=277

39% reduction

32% reduction

Dusser et al. Eur Respir J 2006;27:547-555

MISTRAL: number of

exacerbations/years

P=0.03

Me

an

nu

mb

er

of

ex

ac

erb

ati

on

s/y

ea

r

0

0.5

1

1.5

2

2.5

3

FEV1 ≥ 50% FEV1 < 50%

Placebo

1.97

N=209

Tiotropium

1.21

N=217

Placebo

2.70

N=296

Tiotropium

1.83

N=277

P=0.007

Changes (Salmoterol/Fluticasone vs placebo) in

whole population and >50% subgroup

* p<0.05

Sutherland ER. NEJM 2004;350:2689-97.

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Chest Hospital Department

of Health Excutive Yuan

R.O.C

Thanks for your attention!