Ppt Copd 2011 Dr Ana Rima

COPD – The Silent Killer

Chronic Respiratory Disease is a Leading Cause of Chronic Disease Deaths Worldwide

Adapted from: World Health Organization. Preventing chronic diseases: a vital investment. (2005) Available at: http://www.who.int/chp/chronic_disease_report/contents/en/index.html (accessed June 2009).

The World Health Organization (WHO) projected that, in 2005, chronic respiratory disease would be the third-leading cause of deaths from chronic disease

worldwide

Pauwels RA, Rabe KF. Lancet. 2004; 364: 613-620

Change in Death Rates for Cardiovascular and Pulmonary Disease

Tan and NG Chest 2008; 133:517

Prevalence COPD in Asia-Pacific Region

Definition

GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Revised 2011. Available from: http://www.goldcopd.org

• COPD, a common preventable and

treatable disease, is characterized

by persistent airflow limitation that

is usually progressive and associated

with an enhanced chronic

inflammatory response in the

airways and the lung to noxious

particles or gases

• Exacerbations and comorbidities

contribute to the overall severity in

individual patients

REVISED 2011

General considerations for FEV1 decline

FEV1 decline in healthy subjects

FEV1 decline in COPD patients

FE

V1 d

ecl

ine (

mL

)

“normal decline”

“additional decline”

Annual

PotentialRoom for

Improvement

1. Celli BR, MacNee W. Eur Respir J. 2004; 23: 932–946;2. GOLD. Global Initiative for Chronic Obstructive Lung Disease. Updated 2010. Available: www.goldcopd.com

Mechanisms of Airflow Limitation in COPD

(Peripheral Airways)

Adapted from: Barnes P. NEJM 2000; 343; 269

FEV1 decline in COPD:Potentially reversible

mechanisms

Mucus hypersecretion

Smooth musclecontraction

Cholinergic tone

Loss of alveolar attachmentPeribronchial fibrosis

1. Celli BR, et al. Am J Respir Crit Care Med 2008; 178: 332–38;2. Beaucage F, Decramer M, et al. Am J Respir Crit Care Med .2008; 177: A401.

Adapted from: Hansel T/Barnes P. An Atlas of COPD. 2004

Central nervous system

Vagus nerve

Airway epithelium

Parasympatheticganglion

ACh

ACh

AChInflammatory

cell mediators

SubmucosalglandCholinergic

receptors

Irritants(e.g. cigarette smoke, bacteria, viruses)

Airway smooth muscleconstriction

MucusHypersecretion

Pathophysiology of COPD:Vagal Nerve System

Pre-ganglionicnerve

Parasympatheticganglion

Post-ganglionicnerve

Airway smoothmuscle

Nicotinic receptors (+)

M1 receptors (+)

M2 receptors (–)

M3 receptors (+)ACh

Hansel T / Barnes P. An Atlas of COPD. 2004

Cholinergic Receptor Subtypes in Airways

Ideal anti cholinergi

c

FEV1 Model of Disease Progression in COPD

100%

75%

50%

25%

0%25 50 75

Age (years)

FE

V1

(% o

f v

alu

e at

ag

e 2

5)

Moderate

Severe

Very Severe

COPDStages

Treatment

Adapted from Fletcher C and Peto R, BMJ 1977; 1:1645-1648. Imagery courtesy O’Donnell D

Diagnosis

Severe COPD

The Progression of COPD

Mild COPD

What can we do ???What can we do ???

Key Indicators for Considering a Diagnosis of COPD

Buku Lengkap Diagnosis dan Penatalaksanaan PPOK PDPI, Juli 2011

Stable COPD Treatment Goals


UPLIFT : FEV1 Over 4-Year Trial Duration

*P<0.05 vs control. †Difference, tiotropium – control. BD, bronchodilator.

Total cohort2Asian cohort1

Δ rate of decline:†

0 mL/yr pre-BD (P=0.95)2 mL/yr post-BD (P=0.21)


-2 mL/yr pre-BD (P=0.83)

5 mL/yr post-BD (P=0.54)

Japanese cohort1

Day 30

Post-BDTiotropium (n=2516)Control (n=2374)

*

*********

48

Month

423630241812601

Pre-BDTiotropium (n=2494)Control (n=2363)

* * * * * * * *

Tiotropium Control

48423630241812601

Day 30

**

Month

0.00

0.80

0.90

1.00

1.10

1.20

1.30

1.40

1.50

FE

V1 (L

)

Tiotropium Control

** * * * *

*********Pre-BDTiotropium (n=152)Control (n=145)



11 mL/yr pre-BD (P=0.24)13 mL/yr post-BD (P=0.16)

48423630241812601

Day 30Month

0.00

0.80

0.90

1.00

1.10

1.20

1.30

1.40

1.50 Tiotropium Control

Pre-BDTiotropium (n=45)Control (n=43)

** * * * * * *

*

*******

0.00

0.80

0.90

1.00

1.10

1.20

1.30

1.40

1.50


1Fukuchi Y, et al. Respirology 2011; 16: 825-835; 2Adapted from Tashkin DP, et al. N Engl J Med 2008;359:1543-1554.

Significant lung function improvement with tiotropium in total, Asian and

Japanese cohort

*P<0.05 vs. control. Repeated measure ANOVA was used to estimate means. Estimated means are adjusted for baseline measurements. Patients with ≥2 acceptable SGRQ Total Scores after Month 6 were included in the analysis.

UPLIFT : SGRQ Total Score

= 2.3-3.3 units

Asian Cohort1 Total Cohort2

= 1.5-6.1 units

6 12 18 24 30 36 42 480

Month

* * * * * * * *

6 12 18 24 30 36 42 480

Month

Imp

rove

men

t

* * * *

= 1.1-6.2 units

Japanese Cohort1

6 12 18 24 30 36 42 480

Month

** *

35

40

45

50

SG

RQ

To

tal

Sco

re (

Un

its)

Tiotropium (n=184)

35

40

45

50

Control (n=178)Tiotropium (n=48)Control (n=43)

Tiotropium (n=2478)Control (n=2337)

35

40

45

50

1Fukuchi Y, et al. Respirology 2011; 16: 825-835; 2Adapted from Tashkin DP, et al. N Engl J Med 2008;359:1543-1554.

Significant SGRQ improvement with tiotropium in total, Asian and Japanese

cohort

The UPLIFT Lesson

Similar to the overall cohort, 4 years treatment with tiotropium provided the following benefits in the subgroup of COPD patients from Asia (Improved lung function, Improved HRQoL, Reduced exacerbations)

These data indicate that tiotropium may be used in patients from Asia in accordance with current international treatment guidelines

Tiotropium is beneficial to COPD patients of various severities (GOLD stages II to IV) and has clearly demonstrated benefit to GOLD stage II patients

1Fukuchi Y, et al. Respirology 2011; 16: 825-835

Exacerbations

Increased mortality with exacerbation

hospitalizations

Increased health resource

utilization and direct costs

Reduced health-relatedquality of life

Accelerateddeclinein FEV1

The Clinical Course of COPD:Consequences of Exacerbations

Systemic inflammation increases during ECOPD potential mechanism to explain the increased risk of vascular events

Plasma levels of the cardiac biomarkers NT-proBNP and troponin T were abnormal in a significant number of ECOPD patients hospitalized both markers predicted mortality

Patients with COPD had increased circulating platelete-monocyte aggregates further increased during ECOPD

Fabbri LM, et al. Thorax. 2011; 66(9): 745-747

POET-COPD®: Tiotropium Significantly Delayed Time to First

ExacerbationP

rob

abili

ty o

f C

OP

D e

xace

rbat

ion

(%

)

Time to event (days)0

50

030 60 90 120 150 180 210 240 270 300 330 360

Hazard ratio = 0.83*(95% CI, 0.77, 0.90)P<0.001 (log-rank test)

Tiotropium 3707 3369 3136 2955 2787 2647 2561 2455 2343 2242 2169 2107 1869

Salmeterol 3669 3328 3028 2802 2605 2457 2351 2251 2137 2050 1982 1915 1657

No. of patients at risk:

45

40

35

30

25

20

15

10

5

TiotropiumSalmeterol

*Cox regression adjusted for (pooled) centre and treatment.

17%Risk

difference

Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.

Pro

bab

ility

of

ho

spit

aliz

ed

CO

PD

exa

cerb

atio

n (

%)

Time to event (days)0

0

5

10

15

20

30 60 90 120 150 180 210 240 270 300 330 360

POET-COPD®: Tiotropium Significantly Delayed Time to First

Severe ExacerbationTiotropiumSalmeterol

Hazard ratio = 0.72*(95% CI, 0.61, 0.85)P<0.001 (log-rank test)

Tiotropium 3707 3564 3453 3359 3285 3217 3177 3125 3066 3017 2977 2984 2663

Salmeterol 3669 3502 3362 3244 3172 3080 3032 2982 2921 2870 2834 2806 2489

No. of patients at risk:

28%Risk

difference

*Cox regression adjusted for (pooled) centre and treatment. Vogelmeier C et al. N Engl J Med 2011;364:1093-1103.

Tiotropium Reduced Number of Exacerbations

0.64

0.54

0.09

0.72

0.59

0.13

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

All exacerbations Moderateexacerbations

Severeexacerbations

Ad

jus

ted

ye

arl

y r

ate

RR 0.89*

(95% CI 0.83, 0.96)P=0.002 RR 0.93*

(95% CI 0.86, 1.00)P=0.048

RR 0.73*

(95% CI 0.66, 0.82)P<0.001

Tiotropium

Salmeterol

RR=rate ratio.

*Poisson regression correcting for overdispersion and adjusted for treatment exposure.


POET-COPD®: Time to First Exacerbation by Subgroup Consistent with Overall Cohort

Hazard ratio for at least one COPD exacerbation

0.4 0.6 0.8 1 1.2 1.4Favours tiotropium Favours salmeterol

Stage II 561/1781 635/1833 0.88 (0.79, 0.99)

455/1230≥20 to <25 501/1254 0.89 (0.79, 1.02)

Age group

Characteristic Tiotropiumn/N

Salmeteroln/N

Hazard Ratio(95% CI)

Sex

GOLD stage

Smoking status

BMI group

ICS use at baseline

237/655<55 y 258/665 0.88 (0.74, 1.05)484/1462≥55 to <65 y 522/1426 0.87 (0.77, 0.98)556/1590≥65 y 634/1578 0.83 (0.74, 0.93)

913/2759Male 1016/2747 0.86 (0.78, 0.94)364/948Female 398/922 0.84 (0.73, 0.97)

Stage III 589/1597 627/1545 0.86 (0.77, 0.97)Stage IV 127/329 152/291 0.64 (0.50, 0.81)

678/1929Noncurrent 746/1896 0.84 (0.75, 0.93)599/1778Current 668/1773 0.87 (0.78, 0.97)

105/286<20 134/271 0.66 (0.51, 0.85)

424/1276≥25 to <30 468/1284 0.87 (0.76, 0.99)293/915≥30 311/860 0.85 (0.72, 1.00)

Yes 785/1986 839/1955 0.87 (0.79, 0.96)No 492/1721 575/1714 0.82 (0.73, 0.92)

*Subgroup by treatment interaction. GOLD=Global Initiative for Chronic Obstructive Lung Disease; BMI=body-mass index; ICS=inhaled corticosteroid.

*n=no. patients with event; N=total no. patients.

0.76

P-value*

0.83

0.05

0.64

0.17

0.41


Tiotropium was significantly more effective across almost all subgroup compared to

salmeterol

POET-COPD®: Discontinuing ICS did not Increase Rate of Exacerbations*

Tiotropium Salmeterol

n Exacerbation rate

(95% CI)

n Exacerbation rate

(95% CI)

Continued ICS during trial

1452

0.78(0.73, 0.85)

1401

0.81(0.75, 0.88)

Discontinued ICS during trial 395 0.67

(0.57, 0.79) 416 0.86 (0.74, 0.99)

*Analysis in subset of patients who were receiving ICS at baseline. ICS=inhaled corticosteroid.


POET-COPD®: More Patients Receiving Concomitant ICS Experienced Pneumonia

• 180 reported pneumonia cases

– 158 (87.8%) radiologically confirmed 70 in the tiotropium group

88 in the salmeterol group

– Higher numbers of patients with ≥1

radiologically confirmed pneumonia were

receiving concomitant ICS for ≥1 day on

treatment n=89, 2.7% (n=72 hospitalized) – concomitant ICS

n=59, 1.5% (n=46 hospitalized) – no concomitant ICSVogelmeier C et al. N Engl J Med 2011;364:1093-1103.

The POET-COPD Lesson

Tiotropium was significantly more effective than salmeterol in almost all assessed exacerbation endpoints and across all major patient subgroups

Addition of ICS did not affect the outcome of exacerbation; prevention of exacerbations by tiotropium alone appears to be efficient

Adverse events seen in the POET-COPD® trial were consistent with the well-established, long-term safety profile of tiotropium

Stable COPD Treatment Goals


UPLIFT 4 years study

UPLIFT 4 years study

UPLIFT 4 years study and POET-COPD 1 year

study

Management of COPD in Indonesia


Spiriva ®

early treatment start from

stage II COPD

Spiriva ®

early treatment start from

stage II COPD

Berotec®

Combivent UDV ®

Take Home Messages

Cholinergic tone is the basic of COPD patophysiology

Early intervention – impact disease progression

The UPLIFT and POET – COPD trials of support initiating tiotropium (Spiriva®) as the preferred foundation maintenance therapy as it improves lung function, improves quality of life as well as reduces the risk of COPD exacerbations

In case of exacerbations, fenoterol (Berotec®) or combination of ipratropium/salbutamol (Combivent UDV®) can be used as reliever in every stage of COPD

Thank You

Ppt Copd 2011 Dr Ana Rima

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