trend of copd management

Trend of COPD management

รศ. นพ. วัชรา บุญสวัสด์ิ M.D., Ph.D.ประธานเครือขายคลินิคโรคหืดและปอดอุดก้ันเรื้อรังแบบงาย

ภาควิชาอายุรศาสตร คณะแพทยศาสตรมหาวิทยาลัยขอนแกน

ó COPD guideline

ó Changing concept in COPD treatment

ó Easy COPD clinic

Contents

2

3

4

Definition of COPD

1 211

5

3 48

6 7

910

Asthma

COPD

Airflowobstruction

EmphysemaChronicbronchitis

Reversible FEV1 Δ>15%

Irreversible FEV1 Δ <15%

5

Definition of COPD

ó COPD is a disease state characterized by airflow limitation that is not fully reversible.

ó The airflow limitation is usually both progressive and associated with an abnormal inflammatoryresponse of the lungs to noxious particles or gases.

6

FEV1

Force Expiratory Volume in 1 secondFVC

Force Vital Capacity

Post Bronchodilator FEV1 /FVC < 70 %

การตรวจสมรรถภาพปอด (spirometry)

7

8

9

Systemic effect of COPD

ó Systemic inflammation

ó Weight loss

ó Skeletal muscle dysfunction

10

Traditional view of COPD progression

Age (year)

FEV1

% o

f val

ue a

t age

25

yr

100

75

50

25

5025 75

Death

Disability

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

Nonsmokers20-30 ml/year

COPD60 mL/year

symptoms

11

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 Deconditionin

g

Systemic effect of COPD•Weight loss•Skeletal muscle dysfunction

12

N Engl J Med 2004;350:1005-12.

BODE index

13

เปาหมายของการรักษา

ó ปองกันหรือชะลอการดําเนินโรคó บรรเทาอาการ โดยเฉพาะอาการหอบเหนื่อยó ทําให exercise tolerance ดีขึ้นó ทําใหคุณภาพชีวิตดีขึ้นó ปองกันและรักษาภาวะอาการกําเริบó ปองกันและรักษาภาวะแทรกซอนó ลดอัตราการเสียชีวิต

14

Treatment

ó Retard the progression of airflow obstruction

ó Minimizing airflow obstruction

ó Prevent complication

ó Optimizing functional capacity

15

Treatment

ó Retard the progression of airflow obstruction

ó Minimizing airflow obstruction

ó Prevent complication

ó Optimizing functional capacity

16

Anthonisen NR, JAMA,1994;2721497-150517

uropean espiratory ocietysstudyon hronic bstructive

ulmonary isease EUROSCOP)

18

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

Placebo

budesonide

Effect of inhaled Triamcinolone on the decline of pulmonary function in COPD

Lung Health Study. N Eng J Med 2000;343:1902-9

n=1116

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.

Treatment

ó Retard the progression of airflow obstruction

ó Minimizing airflow obstruction

ó Prevent complication

ó Optimizing functional capacity

Bronchodilators

1. Anticholinergics

2. B2 agonist

3. Theophylline

Corticosteroidsó Oraló Inhaled

Pharmacotherapy

22

Management of Stable COPD

Pharmacotherapy: Bronchodilators

§ Bronchodilator medications are central to the symptomatic management of COPD (Evidence A). They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms and exacerbations.

§ The principal bronchodilator treatments are ß2- agonists, anticholinergics, and methylxanthines used singly or in combination (Evidence A).

§ Regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators (Evidence A).

Management of Stable COPD

Pharmacotherapy: Glucocorticosteroids

§Pro

§Con

25

uropean espiratoryocietysstudyon hronic

bstructive ulmonaryisease EUROSCOP)

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

Placebo

budesonide

26

27

28

Sin DD. AJRCCM 2001;164:580-58429

Sin DD. AJRCCM 2001;164:580-584

Inhaled corticosteroids and the risk of readmission and mortality

Thorax 2005;60:992–997.

D D Sin,

31

2.5

1.9

1.2

1.71.4

1.2

0

0.5

1

1.5

2

2.5

3

<1.25 1.25-1.54 >1.54

FEV1

Exac

erba

tions

per

yea

r

PlaceboFluticasone

ISOLDE. BMJ 2000;320:1297-130332

Short acting bronchodilator as needed

Regular bronchodilator treatmentinhaled corticosteroids

Oxygen therapy

Regular bronchodilator treatmentConsider inhaled corticosteroids

Regular bronchodilator treatment

FEV1>80%

FEV1 30-50%

FEV1 50-80%

FEV1 <30%

33

Short acting bronchodilator as needed

Regular bronchodilator treatmentinhaled corticosteroids

Oxygen therapy

Regular bronchodilator treatmentConsider inhaled corticosteroids

Regular bronchodilator treatment

FEV1>80%

FEV1 30-50%

FEV1 50-80%

FEV1 <30%

LABAICS

LABAICS

Oxygen therapy

34

Short acting bronchodilator as needed

ICS

Intermittent

Moderate persistent

Mild persistent

Severe persistent

LABAICS

LABAICS

prednisolone

35

Treatment

ó Retard the progression of airflow obstruction

ó Minimizing airflow obstruction

ó Prevent complication

ó Optimizing functional capacity

36

Treatment

ó Retard the progression of airflow obstruction

ó Minimizing airflow obstruction

ó Prevent complication

ó Optimizing functional capacity

37

Management of Stable COPD

Non-Pharmacologic Treatments

§ Rehabilitation: All COPD patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

§ Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).

50/100 50/250 50/500

Seretide Diskus (Salmeterol +Fluticasone)

199939

What is Symbicort®?

Two strengths: • Symbicort® Turbuhaler® 160/4.5 µg• Symbicort® Turbuhaler® 80/4.5 µg

budesonide and formoterolin a single inhaler

40

41

Study designRun-in Randomisation

–0.5 0 1 2 3 Months 6 9 12

Clinic visits 1–8

Treatment

(Symbicort® Turbuhaler® ) bid

1 2 3 4 5 6 7 8

Terbutaline as reliever for all patients

ORAL PRED +FORM

Symbicort Turbuhaler 160/4.5 µg delivers the same amount of budesonide and formoterol as the corresponding Turbuhaler monoproducts

(Pulmicort® Turbuhaler®) 400 µg bid

(Oxis® Turbuhaler®) 9 µg bid

Placebo

42

43

Time to first exacerbation

44

*1.4

1.6

1.91.8

*p<0.05 vs placebop=0.015 Symbicort vs formoterol

Symbicort reduces severe exacerbationsMean 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

45

Mean no. of days on oralsteroids/patient/year

p=0.022 Symbicort vs budesonidep=0.007 Symbicort vs formoterol

Symbicort reduces days on oral steroids

***p<0.001 vs placebo

11.08

9.699.06

***6.52

0

2

4

6

8

10

12

PlaceboFormoterolBudesonideSymbicort

46

47

Management of Stable COPD

Pharmacotherapy: Glucocorticosteroids

§ The addition of regular treatment with inhaledglucocorticosteroids 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).

§ An inhaled glucocorticosteroid combined with a long-acting ß2-agonist is more effective than the individual components (Evidence A).

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TOwards a Revolution in COPD Health – the TORCH trial

SFC 50/500 µg bd (N=1533)

TORCH: study design

SAL 50 µg bd (N=1521)

Placebo (N= 1524)3-year study duration

2 week run-in

FP 500 µg bd (N=1534)

Vestbo et al. Eur Respir J 2004; Calverley et al. NEJM 2007

TORCH: main objectivesPrimary objective

– The effect of SFC 50/500 µg vs placebo on all-cause mortality over 3 years in patients with moderate-to-severe COPD

Secondary objectives

– The effect of SFC 50/500 µg on the rate of moderate and severe exacerbations

– The effect of SFC 50/500 µg on health status (SGRQ)

Vestbo et al. Eur Respir J 2004Calverley et al. NEJM 2007SGRQ = St. George’s Respiratory Questionnaire

Vertical bars are standard errors

15241533

14641487

13991426

12931339

Numberalive

02468

1012141618

0 12 24 36 48 60 72 84 96 108 120 132 144 156Time to death (weeks)

Probability of death (%)

SFC 12.6%Placebo 15.2%

HR 0.825, p=0.05217.5% risk reduction

2.6% absolute reduction

Calverley et al. NEJM 200752

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

1. Jenkins C et al. Poster (227) presented at ERS 2007.

SFC: impact of exacerbation history (TORCH)1

Exacerbation history: impact of SFC % reduction

No recalled exacerbations 19

1 exacerbation in previous year 26

≥2 exacerbations in previous year 31

• In patients with a history of more frequent exacerbations, there were trends to higher rates overall, and a greater effect of treatment

• Reductions in exacerbation rates associated with treatment are not dependent on a history of frequent exacerbations, and the benefits of SFC on exacerbations are still seen in patients who had no history of an exacerbation in the previous 12 months

SGRQ total score

–5–4–3–2–1

0123

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 ofsubjects

1149114811551133

854906942941

781844848873

726807807814

675723751773

635701686731

569634629681

SFC††

Calverley et al. NEJM 2007

Post-bronchodilator FEV1Adjusted mean change FEV1 (mL)

0 24 48 72 96 120 156Time (weeks)

–150

–100

–50

0

50

100

Placebo SALM FP

**

*†

SFC

1524152115341533

1248131713461375

Number ofsubjects

1128121812301281

1049112711571180

979105410781139

906101210061073

819934908975

*p < 0.001 vs placebo; †p < 0.001 vs SALM and FPCalverley et al. NEJM 2007

SFC slows the rate of decline of lung function over 3 years (TORCH)

*p=0.003 vs placebo, **p<0.001

Note: this was a post hoc analysis

-50

-60

0

-20

-30

-40

-10

-55

Placebo

-42*

Sal

-42**

FP

-39**

SFC

Treatment arm

Adj

uste

d ra

te o

f dec

line

(ml/y

r)

-30

Non-COPD patient

TORCH study1. Celli BR et al. Am J Respir Crit Care Med 2008; 178: 332–338.57

58Jenkins. Respir Res 2009: 59

59

Jenkins. Respir Res 2009: 59

60

Jenkins. Respir Res 2009: 59

61

Summary of efficacy resultsSFC improved survival in COPD

This was supported by

– Significantly fewer exacerbations compared with components or placebo

– Significantly fewer hospitalisations compared with placebo

– Significant improvements in health status superior to components and placebo

– Significant improvements in lung function superior to components and placebo

1. Calverley et al. NEJM 20072. Jones et al. Chest 2006

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.

63

Definition of COPD: GOLD2006

• COPD is a preventable and treatabledisease 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.

64

COPD treatment in practice

ó 62 year oldó หอบเหน่ือยมา 1ปó สูบบุหรี่ 1 ซองมา40 ป

ó PE : wheezing both lung

ó Dx –COPD

65

66

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Asthma

Episodic respiratory symptomsVariable airflow obstruction

occurring spontaneously, with treatment or after provocation

COPD

Incompletely reversible airflow obstruction

Overlap syndrome

Asthma and COPD—that is, symptoms ofincreased variability of airflow and

incompletely reversible airflow obstruction

•Asthma with chronic bronchitis•Chronic obstructive bronchitis•Asthma with permanent obstruction •COPD with a reversible component

Asthma vs COPD

69

Thoracic Society of Thailand:COPD Guidelines

70

Spirometry is not widely used in Thailand

71

Can we use Peak Flow meter to monitor COPD?

72

Easy COPD Clinic

73

ó สูบบุหรี่ Pack-year= จํานวนบุหรี่ท่ีสูบในแตละวัน X ระยะเวลา(ป)ó 20ó ไอเรื้อรัง ó เหน่ือยงายó มีว้ีด

CXR

PEFR <80%

Diagnosis COPD

74

75

การประเมินโรค

COPD

Airflow obstruction

Death

Air trapping

exacerbation

Reduced activity

Exercise limitation Deconditionin

g

Systemic effect of COPD•Weight loss•Skeletal muscle dysfunction

FEV1, PEFR

FRC, IC

6 Min walk

Dyspnea score

Exacerbation

ó อาการóExacerbationóDyspnea scoreó PEFRóBMIó 6 minute walk

การประเมินโรค

77

ขณะนี ้อาการเหนื่อยหอบของคุณเปนอยางไรบาง0. ไมมีอาการเหนื่อย เพียงแครูสึกหายใจหอบเฉพาะ ขณะออกกําลังกายอยางหนักเทานั้น

1. หายใจหอบ เม่ือเดินอยางเรงรีบบนพื้นราบ หรือเม่ือเดินขึ้นท่ีสูงชัน2. เดินบนพื้นราบไดชากวาคนอื่นท่ีอยูในวัยเดียวกัน เพราะหายใจหอบ หรือตองหยุดเพื่อหายใจเม่ือเดินปกติบนพื้นราบ

3. ตองหยุดเพื่อหายใจหลังจากเดินไดประมาณ 100 เมตร หรือหลังจากเดินไดสักพักบนพื้นราบ

4. หายใจหอบมากเกินกวาท่ีจะออกจากบาน หรือหอบมากขณะแตงตัว หรือเปลี่ยนเครื่องแตงตัว

Dyspnea score

78

79

www.catestonline.org

nurse

Doctor

nurse

Pharmacist

•Register patients •Assess severity

Treatment

AppointmentRehabilitation

Inhaler technique COPD education

Dyspnea scores

SpirometryFEV1/ FVC <70%วัดความเร็วสูงสุด

6 Min walk

BMI

80

ó COPD Guideline>>>>>GOLD Guidelineó Changing concept in COPD managementó Irreversible vs incomplete reversible airway obstructionó Inflammatory diseaseó Systemic inflammation

ó The TORCH trialó Pharmacotherapy can slow disease progression.ó SFC improve survival, reduce exacerbation, improve QOL ó SFC is effective in moderate COPD (GOLD stage II)

ó COPD is a preventable and treatable diseaseó Easy COPD is easy

Summaries

81