Update in COPD

Management

รศ. นพ. วชรา บญสวสด M.D., Ph.D. ประธานเครอขายคลนคโรคหดและปอดอดกนเรอรงแบบงาย

ภาควชาอายรศาสตร คณะแพทยศาสตร มหาวทยาลยขอนแกน

COPD

โรคปอดอดก นเร อรง

เปนโรคทผปวยท าตวเอง โทษใครไมได

หลอดลมตบไมดขนเมอใหยาขยายหลอดลม (Irreversible airway obstruction)

รกษาไมได

2

Old COPD Guidelines

3

หลอดลมอกเสบเรอรง (Chronic bronchitis)

ถงลมปอดโปงพอง (Emphysema)

โรคหด Asthma

Irreversible FEV1 Δ <15%

Reversible FEV1 Δ>15%

4

Evidence-based COPD Guidelines

5

Definition of COPD

6

COPD is a disease state characterized by

airflow limitation that is not fully reversible.

The airflow limitation is usually both

progressive and associated with an

abnormal inflammatory response of the lungs to noxious particles or gases.

การตรวจสมรรถภาพปอด (spirometry)

FEV1

Force Expiratory Volume in 1 second

FVC

Force Vital Capacity

airflow limitation that is not fully reversible.

Post Bronchodilator FEV1 /FVC < 70 %

8

Systemic effect of COPD

10 Barnes PJ. ERJ 2009:1165

COPD

Airflow obstruction

Death

Air trapping

exacerbation

Reduced activity

Exercise limitation

Deconditioning

infection

Traditional view of COPD progression

Age (year)

FE

V1 %

of

valu

e a

t a

ge 2

5 y

r

100

75

50

25

50 25 75

Death

Disability

Adapted from:Fletcher C,et al.Br Med J.1977;1:1645-1648

Nonsmokers 20-30 ml/year

COPD 60 mL/year

symptoms Stage II: Moderate 50% < FEV1 < 80% predicted

Stage III: Severe 30% < FEV1 < 50% predicted

Stage IV: Very Severe FEV1 < 30% predicted

Stage I: Mild FEV1 > 80% predicted

COPD

Airflow obstruction

Death

Air trapping

exacerbation

Reduced activity

Exercise limitation

Deconditioning

Systemic effect of COPD •Weight loss •Skeletal muscle dysfunction

infection

14

mMRC Dyspnea score

COPD

Airflow obstruction

Death

Air trapping

exacerbation

Reduced activity

Exercise limitation

Deconditioning

Systemic effect of COPD •Weight loss •Skeletal muscle dysfunction

infection

FEV1, PEFR

FRC, IC

6 Min walk CAT

Dyspnea score

Exacerbation

15

None of the existing medications for COPD have been

shown to modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is used to decrease symptoms and/or complications.

Manage stable COPD 2001

Pharmacotherapy

Bronchodilators

1. Anticholinergics

2. B2 agonist

3. Theophylline

Corticosteroids

Oral

Inhaled

PDE4 PLAYS AN IMPORTANT ROLE IN

INFLAMMATION

P P P

P

PDE4 inhibition

PDE4

Adapted from Rabe KF. Expert Rev Resp Med 2010;4: 543–555.

19

European Respiratory Society’s study on Chronic Obstructive Pulmonary Disease (EUROSCOP)

Pauwels R. N Engl J Med 1999;340:1948-53.

Placebo

budesonide

Thorax 2005;60:992–997.

D D Sin,

Inhaled corticosteroids reduce all-cause mortality in COPD.

22

2.5

1.9

1.2

1.7

1.4 1.2

0

0.5

1

1.5

2

2.5

3

<1.25 1.25-1.54 >1.54

Ex

ac

erb

atio

ns

pe

r y

ea

r

FEV1

Placebo

Fluticasone

ISOLDE. BMJ2000;320:1297-1303

Management of Stable COPD

Pharmacotherapy: Glucocorticosteroids

The addition of regular treatment with inhaled glucocorticosteroids to bronchodilator treatment is

appropriate for symptomatic COPD patients with an FEV1 < 50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations (Evidence A).

24

Short acting bronchodilator as needed

Regular bronchodilator treatment inhaled corticosteroids

Oxygen therapy

Regular bronchodilator treatment Consider inhaled corticosteroids

Regular bronchodilator treatment

FEV1>80%

FEV1 30-50%

FEV1 50-80%

FEV1 <30%

25

Short acting bronchodilator as needed

Regular bronchodilator treatment inhaled corticosteroids

Oxygen therapy

Regular bronchodilator treatment Consider inhaled corticosteroids

Regular bronchodilator treatment

FEV1>80%

FEV1 30-50%

FEV1 50-80%

FEV1 <30%

LABA ICS

LABA ICS

Oxygen therapy

Short-acting bronchodilator

prn

Short-acting bronchodilator

regular

Long-acting bronchodilator

Add ICS ( >1 exacerbation)

บทบาทของ

ICS/LABA

27

Rate of moderate and severe

exacerbations over three years

*p < 0.001 vs placebo; †p = 0.002 vs SALM; ‡p = 0.024 vs FP

Mean number of exacerbations/year

1.13

0.97* 0.93*

0.85*†‡

25% reduction

0

0.2

0.4

0.6

0.8

1

1.2

Placebo SALM FP SFC

Treatment

Calverley et al. NEJM 2007

SGRQ total score

–5

–4

–3

–2

–1

0

1

2

3

0 24 48 72 96 120 156

Adjusted mean change SGRQ total score (units)

Time (weeks)

Placebo

SALM *

FP †

*p = 0.057 vs placebo; †p < 0.001 vs placebo; ††p < 0.001 vs placebo, SALM and FP; vertical bars are standard errors

Number of

subjects

1149 1148 1155 1133

854 906 942 941

781 844 848 873

726 807 807 814

675 723 751 773

635 701 686 731

569 634 629 681

SFC ††

Calverley et al. NEJM 2007

C/08/185 August 2008

FEV1 (mL) 1350

1300

1250

1200

1150

1100

0 24 48 72 96 120 156 Time (weeks)

–39 mL/yr

–42 mL/yr

–55 mL/yr

–42 mL/yr

Control

SAL

FP

SFC

Error bars represent 5% and 95% confidence intervals

Rate of decline in lung function over

3 years

Celli et al. Am J Respir Crit Care Med 2008

• SFC significantly reduced the rate of decline in lung function compared with placebo

(39mL/year vs 55mL/year, difference 16mL/year p<0.001)

“…[Seretide] decreas[ed] the excess FEV1 decline attributable to COPD by

approximately half.”

“…halving the excess decline in FEV1 is likely to be clinically important…”

Definition of COPD: GOLD2006

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.

31

เปาหมายของการรกษา

ปองกนหรอชะลอการด าเนนโรค

บรรเทาอาการ โดยเฉพาะอาการหอบเหนอย

ท าให exercise tolerance ดขน

ท าใหคณภาพชวตดขน

ปองกนและรกษาภาวะแทรกซอน

ปองกนและรกษาภาวะอาการก าเรบ

ลดอตราการเสยชวต

Current control

Prevent

Future risk

2009

Exacerbations

33

Patients with frequent exacerbations

Increased risk of

recurrent exacerbations

Increased

inflammation

Lower quality of life Increased mortality rate

Increased likelihood

of hospitalisation

Adapted from Wedzicha JA et al, 2007; Donaldson GC et al, 2006.

Faster disease

progression

GOLD 2011 revision

34

Current symptoms

Fu

ture

ris

ks

MRC 0-1

CAT<10

MRC 2+

CAT 10+

Association of disease severity

and exacerbations

35 Hurst JR(ECLIPSE), NEJM. 363; 1128::2010

36

GOLD 2011 revision

37

Current symptoms

Fu

ture

ris

ks

GOLD 1

GOLD 2

GOLD 3

GOLD 4

Exacerbations / y

0

2

1

>2

MRC 0-1

CAT<10

MRC 2+

CAT 10+

A

D C

B

GOLD 2011 revision

38

Current symptoms

Fu

ture

ris

ks

GOLD 1

GOLD 2

GOLD 3

GOLD 4

Exacerbations / y

0

2

1

>2

MRC 0-1

CAT<10

MRC 2+

CAT 10+

A

D C

B SABA

or

SAMA

LABA

or

LAMA

ICS/LABA

or

LAMA

ICS/LABA

or

LAMA

39

Study design Run-in Randomisation

–0.5 0 1 2 3 Months 6 9 12

Clinic visits 1–8

Treatment

(Budesonide/Formoterol Turbuhaler ) 320/9 ug bid

1 2 3 4 5 6 7 8

Terbutaline as reliever for all patients

ORAL

PRED

+FORM

Symbicort Turbuhaler 160/4.5 g delivers the same amount of budesonide

and formoterol as the corresponding Turbuhaler monoproducts

(Budesonide Turbuhaler®) 320 g bid

(Formoterol Turbuhaler®) 9 g bid

Placebo

40

80

84

88

92

96

100

104

-0.5 1 3 5 7 9 11

Mean F

EV

1, %

of

baseline

Months since randomization

Placebo

Budesonide

Formoterol

Bud/For

***

***

41

Budesonide/formoterol improves morning PEF

1 3 5 7 9 11

Time since randomisation (months)

–22

–17

–12

–7

–2

3

8

Change in morning

PEF (L/min)

from baseline

Budesonide/Formoterol

Budesonide

Formoterol

Placebo ***

***

p<0.001 Symbicort

vs budesonide

***p<0.001 vs placebo

p=0.007 Symbicort

vs formoterol

0 2 4 6 8 10 12

42

Time to first exacerbation

43

*

1.4

1.6

1.9 1.8

*p<0.05 vs placebo

p=0.015 Symbicort vs formoterol

Budesonide/formoterol reduces severe

exacerbations Mean no. of severe

exacerbations/

patient/year

0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Symbicort Budesonide Formoterol Placebo

44

-3

-2

-1

0

1

2

3

4

5

-0.5 0 6 12

Mean c

hange in s

core

Month since randomization

ชอแผนภม

4 Placebo

2 Budesonide

3 Formoterol

1 Bud/For

1

3

2

4

Run-in

* **

***

45

การศกษานสรปวา

การรกษาผปวยใหเตมทตงแตแรกเรมรกษาดวย prednisolone และยาขยายหลอดลม จะท าใหผปวยรสก

ดข นมากอยางรวดเรว

การให Budesonide/formoterol จะรกษาสมรรถภาพปอดทดข นจากการรกษาเตมทดวย prednisolone ลด

อตราการเกดการก าเรบของโรค และเพมคณภาพชวต ดกวาการให Budesonide หรอ formoterolเดยวๆ

46

COPD

Airflow obstruction

Death

Air trapping

exacerbation

Reduced activity

Exercise limitation

Deconditioning

Systemic effect of COPD •Weight loss •Skeletal muscle dysfunction

infection

Bronchodilator

ICS

47

Easy COPD Treatment

Airway obstruction

48

•Prednisolone

•ICS

•LABA

ท าปจจบนใหด เพออนาคตทสดใส

COPD

โรคปอดอดก นเร อรง

เปนโรคทปองกนได แตเราไมไดปองกนใหผปวย (preventable disease)

หลอดลมตบดขนได เมอใหยาขยายหลอดลม แตไมเปนปกต (incomplete reversible airway

obstruction)

รกษาได (treatable disease)

49

เกณฑการใหคะแนน ภาวะหายใจล าบาก (Modified Medical Research Council Dyspnea Score; mMRC)

50

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