Roberto A. RabinovichELEGI/Colt laboratory

Centre for Inflammation Research The University of Edinburgh20

Pulmonary Rehabilitation Clinicians Day

Evidence for early Pulmonary Rehabilitation following hospitalisation for exacerbation of COPD

Centre for InflammationResearch

• Chronic Obstructive Pulmonary Disease is a preventable and treatable state characterized by airflow limitation that is not fully reversible

• The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles and gases, primarily caused by cigarette smoking

• Although COPD affects the lungs, it also produces significant systemic consequences

Chronic Obstructive Pulmonary DiseaseDefinition

ATS/ERS Statement 2004

ATS/ERS Severity

GOLD Post BdFEV1/FVC

FEV1% pred

At risk 0 > 70Cough and

sputum

> 80

Mild I < 70 > 80

Moderate II < 70 50-80

Severe III < 70 30-50

Very severe < 70 < 30

IV < 70 < 30o

< 50 plus CRF

Chronic Obstructive Pulmonary DiseaseClassification

Celli B et al NEJM 2004; 350: 1005

FEV1

6MWD

MRC

BMI

≥65

≥ 350

0-1

>21

0

50-65

250-349

2

<21

1

36-49

150-249

3

2

≤35

≤ 149

4

3

Variable BODE Index Score

Months

0.2

0.4

0.6

0.8

1.0

0 10 30 40 5220

Score 0-2Score 3-4Score 5-6Score 7-10

Chronic Obstructive Pulmonary DiseasePhenotypes

Pro

babi

lity

ofD

eath

Mador MJ, AJRCCM 2000;161: 447-453

Causes for stopping: Fatigue (60%)

no fatiguefatigue

baseline 10 min

40

60

80

100

120

140

Qua

dric

eps

Twitc

hFo

rce

(% o

fBas

elin

e)

Exercise Tolerance in COPDMore than lung function

FatigueNo-fatigue

Saey D et al 2003 Am J Respir Crit Care Dis;168:425

Improvement in FEV1 12%

Qua

dric

eps

stre

ngth

( % o

f res

ting

valu

e)

Time (seconds)Rest 100 200 300 400 500

100

120

80

60

40

20

*+92%

Muscle Dysfunctionexercise tolerance

5

10

15

20

25

30

control COPD

ControlCOPD

Muscle DysfunctionEndurance

Coronell, Eur Respir J 2004;24: 129-136

End

uran

cetim

e (m

inut

es)

*

controlCOPD

Bernard S. , Am J Respir Crit Care Med 1998;158: 629-634

ControlCOPD

20

40

60

80

100

120120

Qua

dric

eps

stre

ngth

(Kg)

Thigh Cross Sectional Area

control COPD20 40 60 80 100 120 140 160

0.4

0.5

0.6

0.7

0.80.9

CSA thigh (cm2)

Muscle mass and strength

Functional disorders

Physio-pathologicalChanges

StrengthResistanceFatigue

Bioenergetics Fiber type distributionCapillarization and O2 deliveryMuscle mass

It is characterized by two different, but possibly related, phenomena:

• Muscle wasting

• Malfunction of the remaining muscle

Chronic Obstructive Pulmonary DiseaseMuscle dysfunction

0

10

20

30

40

50

60

70

Type I Type II

ControlCOPD

%

Jobin J, J Cardiopulm Rehabil, 1998;18(6): 432-437

Physiopathological changesfibre type

05

101520253035404550

CS HADH

ControlCOPD

Maltais F, AJRCCM 1996;153: 288-293

mm

ol/m

in/g

Physiopathological changesBionergetics and oxidative capacity

0

20

40

60

controlCOPD

0

2

4

6

10 20 30 40 50

[Pi]/

[Pcr

]Watt´s

control

Pcr recovery time

Sala E, Am J Respir Crot Care Med 1999;159: 1726-1734

COPD

Tim

e (s

ec)

Physiopathological changesBionergetics and oxidative capacity

0

50

100

150

200

250

ControlesCOPD

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

ControlesCOPD

Capillaries/mm2 Capillaries/fibre

Jobin J, J Cardiopulm Rehabil 1998, 18(6), 432-437

Physiopathological changescapillarisation and O2 transport

PatientsAdmissionsHospitalisationsGP appointmentsDDM of CTC

2.330

4.44.6

23±±±±

0.5162.43.2

2.70.5

3400±±

1.51.2

High LowHealth Resources

(N)

(N)

(dias)

(N)

(mg/d)

Decramer et al ERJ, 1997, 10, 417-423

Muscle DysfunctionHealth resources

30

40

50

60

70

80

90

AgeFEV1DLCO QFPIm

axPEmax

HighLow

% p

red

* #

Decramer et al ERJ, 1997, 10, 417-423

Muscle DysfunctionHealth resources

COPD : is a systemic condition affecting the peripheral muscles

EXERCISE TRAINING : is an intervention directed to re-establish normal muscle function

Pulmonary RehabilitationRationale for exercise training

Meta-analysis n=277 TR, n=242 CO

Lacasse et al., Cochrane database, 2002

Benefits of Exercise TrainingHRQoL

ΔC

RD

Q (p

oint

s)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

DYS FAT EMO MAS

MCID

Benefits of Exercise TrainingExercise tolerance

GuellBendstrup

FinnertyGoldsteinEngström

CockroftWijkstra

CambachBooker

RingbaeckO´Donnell

Troosters

Troosters et al., Am J Respir Crit Care Dis 2005; 172: 19

0 25 50 75 100

6 minutes walking test

MCID

Eaton T et al., Chron Respir Dis 2006; 3: 1-2

Porc

enta

je

0

25

50

75

100

6MWT EST

Troosters et al., Am J Respir Crit Care Dis 2005; 172: 19

0

25

50

75

100

Watt VO2 Const. Crítico

Benefits of Exercise TrainingExercise tolerance

Benefits of Exercise Trainingeffect on exacerbations

Rehab

Control

8

7

5

2

0

Guell R et al. ERJ 2003; 21: 789-94

Group Per patient

250

200

150

100

50

0LTOT

n n

Rehab

Control

Griffiths TL et al. Lancet 2000; 355: 362-368

Days ofhospitalisation

appointments

n

30

20

10

0

n

4

2

0

1

3

Benefits of Exercise Trainingeffect on exacerbations

.25 .5 1.75 1.5

Bahnke(14/12)

Man(20/21)

Global

Murphy(13/13)

Risk of hospitalisation

Puhan M et al. Respir Research 2005; 6: 54

18 m

3 m

6 m

.05 .2 1.0.5 2.0 5.0.1

Risk of death

Benefits of Pulmonary Rehabilitationearly rehabilitation programmes after exacerbations

Spruit, M. A. Thorax, 2003

No exercise training

Teme (Days)

0

75

150

50

125

100

25

175

8 903

Qua

dric

eps

stre

ngth

(Nm

)

Pitta, F. Chest, 2006

Day 3 Day 8

0

150

50

100

200

COPD ExacerbationsImpact on the muscle

*

Exacerbations of COPDEffect on Physical Activity

•Patients with COPD complain about feeling tired and not being able to cope with daily life activities early during exacerbations

Kessler, R. Chest 130:133-142

Day 2 Day 7

0

75

150

50

125100

25

175

1 Month

**

StableCOPD

Pitta, F. Chest, 2006

Tim

e W

alki

ng(m

in)

Garcia-Aymerich Thorax 2006; 61: 772

0.00

0.25

0.50

0.75

1.00

0 5 15 2010

HighModerate

LowVery Low

years

Hos

pita

lisat

ion

Pro

babl

ity

0.00

0.25

0.50

0.75

1.00

0 5 15 2010years

Ris

k of

dea

th

HighModerateLowVery low

Not a good time for a walk…

DyspnoeaWeakness

Acidosis

Corticosteroids

Psychology

Hypoxemia

Physical ActivityEffect of exacerbations of COPD

Pulmonary RehabilitationDuring exacerbations

6MW

D (m

)

Day 1 Day 10 Month 1 Month 2 Month 6Month 3

0

300

600

200

500

400

100

Hospital Home

Behnke M et al 2000 Res Med; 94: 1184

Control

Rehab

Vis

itsto

ER

(%)

0

30

40

50

60

10

20

*

Man W et al 2004 BMJ; 329: 1209

Strength Training

2

5

3

4

6

0

75

25

50

100

D2 D3 D4 D5 D6 D7 D8

Sym

tom

s(0

-10)

Wei

ght(

%1R

M)

Troosters T et al. Am J Respir Crit Care Med, 2010

Pulmonary RehabilitationDuring exacerbations

FatigueDyspnoea

90

120

100

110

0 10 20 30 40

0

0.75

0.25

0.5

Training Control

Qua

dric

eps

stre

ngth

(% d

ay2)

Myo

geni

n/ M

yoD

Troosters T et al. Am J Respir Crit Care Med, 2010

Pulmonary RehabilitationStrength training during exacerbations

ControlTraining

Neder, J. A. Thorax, 2002

400 μs50 Hz

8 s On

20 s Off AmplitudSelectedBy patient

NMES:

• Frequency 50Hz

• Pulse duration 400 μs

• Cycle duty 8/20s On/Off

• Session duration 30 min

• Amplitud (mA) (on tolerance)

• Sessions: 14

Pulmonary RehabilitationNMES during exacerbations

NMES

Pulmonary RehabilitationNMES during exacerbations

Strength Strength

ScreeningWard

Stimulated leg

14 days of stimulation

Control leg

Hospital Home

Giavedoni S et al. ERS 2010

Pulmonary RehabilitationNMES during exacerbations

Stimulatedleg

Controlleg

-30

-20

-10

0

10

20

ΔFu

erza

(%)

*

-5.8 %

7.8 %

Giavedoni S et al. ERS 2010

Pulmonary RehabilitationNMES during exacerbations

-50

0

50

300 550 800 1050 1300

Σ mA

ΔFu

erza

(N)

R=0.94P < 0.05

Giavedoni S et al. ERS 2010

Pulmonary RehabilitationNMES during exacerbations

-20 -10 0 10 20 30 40 50-25

0

25

50

ΔStr

engt

hSt

imul

ated

leg

(% B

asal

)

Δ Strength Control leg(% Basal)

Favours NMES

Favours Control

Giavedoni S et al. ERS 2010

Pulmonary RehabilitationNMES during exacerbations

Pulmonary RehabilitationThe more, the best

Pulmonary RehabilitationIntensity

-35

-30

-25

-20

-15

-10

-5

0

Lact

ate

VE VO2

VCO

2

VE/V

O2

HR

-35

-30

-25

-20

-15

-10

-5

0

Lact

ate

VE VO2

VCO

2

VE/V

O2

HR

High Intensity Training Low Intensity Training

% c

hang

epo

st-tr

aini

ng

Casaburi Am Rev Respir Dis. 1981;144:1220

Pulmonary RehabilitationDuration

• Short programmes (6-8 weeks) are effective in improving outcomes

• However a key goal of pulmonary rehabilitation is to change patient’s behavior

6MW

D (%

Pre

d)

3 Months 6 Months

0

60

80

100

20

40

% T

ime

Wal

king

3 Months 6 Months

0

30

40

50

60

10

20

Pitta F et al. CHEST 2008; 134: 273

*

-1.6

-1.4

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

ESWT CRQt CRQd CRQf CRQe CRQm

Pulmonary RehabilitationDuration

7 w

eeks

–4

wee

ks

Green et al. Thorax 2001; 56:143-5

505510515520525530535540545550555

Pulmonary RehabilitationDuration

met

ers

Berry et al. J Cardiop Rehab 2003; 23:60-8

0

10

20

30

40

50

60*

*

*

seco

nds

6MWT Steps Overhead

start 6 months 18 months

-30

-20

-10

0

10

20

30

ΔC

RD

Q (p

oint

s)

start 6 months 18 months

-150

-100

-50

0

50

100

150

Δ 6

MW

D (m

)

Pulmonary RehabilitationEffect of 6 month (60sessions)

Troosters et al. AJM 2000; 109(3):207-12

Trainingcontrol

Longer pulmonary rehabilitation programs (beyond 12 weeks) produce greater sustained benefits than shorter programs (ACCP/AACVPR)

Conclusions

• COPD is a complex disease affecting the lungs but incurring in several systemic

effects such as muscle dysfunction

• Muscle dysfunction, together with lung function impairment, causes exercise

intolerance

• Pulmonary rehabilitation, particularly exercise training, is an intervention aimed at

restoring normal muscl function

• PR improves exercise tolerance, HRQoL and improves rate of exacerbations and

hospitalisation days

• Early PR has the same beneficial effects that PR for stable COPD patients and

may have an impact on survival

Conclusions

• Strength training and NMES may help preventing muscle dysfunction during

exacerbations and incur beneficial effects for the patients

• High intensity programmes are preferable to low intensity programmes since

achieve greater effects

• Longer programmes seems to achieve greater effect than shorter programmes

• It is generally believed that longer programes yield more endurable training effects

Roberto A. RabinovichELEGI/Colt laboratory

Centre for Inflammation Research The University of Edinburgh20

Pulmonary Rehabilitation Clinicians Day

Evidence for early Pulmonary Rehabilitation following hospitalisation for exacerbation of COPD

Centre for InflammationResearch