Transcript Exercise training after lung transplant

Exercise training after lung
transplant
Lisa Wickerson BSc PT, MSc(c)
Lung Transplant Program
Toronto General Hospital
Canadian Respiratory Conference
April 28-30,2011
Disclosure of potential conflicts of interest
None to declare
Learning objectives
 Describe the physiological limitations to exercise in lung transplant
recipients
 Identify the evidence for exercise training in improving functional
outcomes following lung transplantation
 Recognize the specific components and structure of exercise training
programs in lung transplant centres across Canada
Lung transplantation
 Established treatment option for a wide range of end-stage lung diseases
(COPD, restrictive lung disease, cystic fibrosis, pulmonary hypertension)
 1499 lung transplants performed in Canada between 2000-2009
 180 lung transplants performed in 6 Canadian transplant programs in 2010
Goals of transplant:
 Decrease disabling symptoms
 Improve functional capacity
 Improve health-related quality of life
 Increase life expectancy
CIHI Canadian Organ Replacement Register 2011
Functional capacity before lung transplant
Lung function
 Obstructive lung disease (FEV1 < 25%pred)
 Restrictive lung disease ( VC and TLC < 65%pred)
 Septic lung disease (FEV1 < 30%pred)
Maximal exercise capacity
 Severe limitation (VO2 peak 20-32%pred)
 Ventilatory limitation present
Functional exercise capacity
 6-minute walk test < 400m
 Vascular lung disease (NYHA functional classes III-IV)
Other
 Resting hypoxemia/ oxygen dependency
 Very low physical functioning subscales on HRQOL
questionnaires (i.e. SF 36)
Lung function after lung transplant
Single Lung transplant
(SLTx)
COPD
• Obstructive defect (FEV1 50-60%)
Restrictive lung disease
• Restrictive defect (FEV1 80%)
• Moderately decreased DLCO (62%)
• Mild desaturation on exertion
Pulmonary Hypertension
• Decreased DLCO
• Very mild restriction
Usually no further improvement after
6 months
Double Lung transplant
(DLTx)
•
•
•
Mild restriction
Mild decrease DLCO
No desaturation on exertion
* Ventilatory
limitation would be indicative
of a pathology (infection, rejection, BOS,
airway stricture)
Spirometry can continue to improve for up to
2 years
Maximal exercise capacity after lung transplant
Results of maximal symptom-limited cardiopulmonary exercise testing:
Low peak oxygen consumption
(VO2peak 40-60% predicted)
Low peak work rate
(Wpeak < 40% predicted)
Early anaerobic threshold
(30% of VO2 peak)
 Exercise terminated at similar intensity and symptoms regardless of pre-
transplant lung disease or transplant procedure (single or double lung)
 Persistent limitations seen in recipients up to 2 years post lung transplant
Williams et al., 1992, Orens et al., 1995, Schwaiblmair et al., 1999, Evans et al., 1997
What is the nature of exercise
limitation in lung transplant
recipients?
Physiological limitations to maximal exercise
Exercise limitation
Ventilatory
- Adequate ventilation
- Adequate gas exchange
- Mild defects in SLTx
Peripheral
Cardiac/ vascular
-Adequate HR, SV
-Mild anemia
-Decreased RVF in
SLTx with PHTN
Abnormal oxidative capacity of
skeletal muscles
• Impaired oxygen uptake
• Impaired oxygen utilization
• Intrinsic abnormalities
Peripheral muscle function
Measures
Findings
Muscle biopsies
•
•
•
•
Lower proportion of Type 1 muscle fibres
Low mitochondrial oxidative enzyme activity
Higher glycolytic enzyme activity
Low ATP production rate
Arterial blood sampling
•
Abnormal potassium regulation
31P-MRS
•
•
Low resting muscle pH
Earlier drop in intracellular pH with exercise
NIRS
•
Smaller drop in hemoglobin and myoglobin oxygen saturation during
exercise
MRI
•
•
Decreased muscle volume
Increased intramuscular fat infiltration
•
•
Decreased peak torque
Decreased isometric endurance
Non-invasive
Computerized dynamometry
Evans et al, 1997, Mathur et al, 2008, Tirdel et al, 1998, Wang et al, 1999, McKenna et al, 2003
When does peripheral muscle function
deteriorate in lung transplant recipients?
Post-transplant peripheral muscle dysfunction
Peripheral muscle
dysfunction
Pre-operative
factors
Post-operative
factors
Peri-operative
factors
Pre-transplant peripheral muscle dysfunction
Muscle changes observed in chronic lung disease
 Decreased muscle mass (cross-sectional area)
 Decreased muscle strength and endurance
 Increased fatigability (decreased twitch force and mandatory voluntary
contraction)
 Increased reliance anaerobic metabolism




Decreased proportion of type 1 fibres
Decreased muscle capillarity
Early onset lactic acidosis
Decreased concentration of oxidative enzymes
ATS/ERS Am J Respir Crit Care Med 1999
Pre-transplant peripheral muscle dysfunction
Contributing factors
 Chronic lung disease






Nutritional status/ catabolic conditions
Corticosteroid use
Oxidative stress
Systemic inflammation
Exacerbations of disease
Deconditioning / decreased physical activity
 General


Comorbidities
Aging
 End-stage lung failure


Mechanical ventilation, ICU admission
Bridge to transplant (Novalung)
Pre-transplant peripheral muscle dysfunction
Healthy subjects (open bars), control patients with COPD (hatched bars), patients with steroid- induced
myopathy (closed bars).
Decramer et al. Am J Respir Crit Care Med 1996
Post-transplant peripheral muscle dysfunction

Thigh muscle volume and composition,
strength and endurance assessed in 6 stable
SLTx recipients compared with 6 COPD
controls

Similar muscle mass, composition and
strength between groups

Quadriceps endurance tended to be lower
in lung transplant recipients
Mathur et al. Cardiopulm Phys Ther J 2008
Post-transplant peripheral muscle dysfunction
Peri-operative issues
• Ischemic injury
• Allograft quality
• Protein catabolism (response to sepsis)
• Critical illness myopathy / use of neuromuscular blocking agents
• Systemic organ dysfunction
• Immobilization / prolonged hospitalization
• Nutritional status
• Infection
• Rejection
Post-operative/ long term issues
• Infection
• Rejection (acute, chronic)
• Medications (calcineurin inhibitors, corticosteroids)
• Decreased physical activity
Post-transplant peripheral muscle dysfunction
A cohort study of 36 lung transplant recipients (15 SLTx, 21 DLTx)
Pre-LTX
BMI
FEV1
6MWD
QF
kg/m2
L
% pred
m
% pred
% pred
*p < 0.05 vs. pre-LTX. †p < 0.05 vs. post-LTX
22.7 ± 4.2
0.85 ± 0.47
31 ± 15
311 ± 124
45 ± 19
72 ± 30
Post-LTX
Post
Rehabilitation
21.7 ± 4.2
1.96 ± 0.85*
70 ± 21*
320 ± 138
46 ± 19
51 ± 28*
23.1 ± 3.7
2.20 ± 0.99*
78 ± 25*
449 ± 128*,†
65 ± 17*,†
59 ± 26*,†
.
Maury et al. Am J Transplant 2008
Post-transplant peripheral muscle dysfunction
• Significant negative
relationship between time
spent in ICU/medium care
unit (MC) and reduction in
skeletal muscle force
• Linear regression analysis
suggest a decline of 0.8Nm
of quadriceps force/day
Maury et al. Am J Transplant 2008
Exercise limitation post organ transplantation
Similar exercise profiles seen in heart, kidney and liver transplant
recipients
 Decreased VO2peak
 Early anaerobic threshold
 Absence of circulatory or ventilatory limitation
Common to all organ transplants
 Pre-transplant



Deconditioning
Central limitations to exercise
Months to years of chronic disease
 Post-transplant


Prolonged hospital stay
Immunosuppression medications ( calcineurin inhibitors, corticosteroids)
To what extent can exercise training
improve exercise capacity and peripheral
muscle function in lung transplant
recipients?
Systematic review of exercise training after lung
transplant
Author
Study
Design
Sample
Size
Interventions
Outcome
Measures
Significant Findings
Braith
(2007)
RCT
30
Alendronate and lumbar
resistance exercises
Lumbar BMD
-BMD 14.1± 3.9% below baseline (controls)
-BMD 10.8±2.3% above baseline (alendronate +
resistance)
Mitchell
(2003)
RCT
16
Lumbar resistance
exercises
Lumbar BMD
-BMD 19.5% below baseline (controls)
-BMD 5 % below baseline (intervention)
Munro
(2009)
Prospective
cohort
36
Aerobic & resistance
exercise
6MWD
FEV1, FVC
SF 36
Increase in 6MWD, FEV1 and FVC, HRQOL
Maury
(2008)
Prospective
cohort
36
Aerobic & resistance
exercise
6MWD
QF, HGF
FEV1
Increase in 6MWD, QF, HGF
Stiebellehner
(1998)
Prospective
cohort
9
Aerobic exercise
VO2 peak
Peak power output
Increase in VO2 peak and peak workload
Ross
(1993)
Prospective
cohort
8
Aerobic exercise
VO2max
Hemo-dynamic
responses
Increased VO2max and work rate
Guerrero
(2005)
Controlled trial
(healthy
controls)
12
Aerobic exercise
Mitochondrial
respiration
Wickerson
et al.
J Heart
Lung Transplant
2010
Significant
increase
in bioenergetics
at cellular
level,
Wmax , endurance time
Wickerson et al. J Heart Lung Transplant 2010
Exercise prescriptions
Study
Mode
Duration Frequency Intensity
Progression
Braith
(2007)
Lumbar extension
training
6 months
1/week
1 set 10-12 reps to fatigue
Increase load 5% once
12 reps achieved
Mitchell
(2003)
Lumbar extension
training
6 months
1/week
1 set 15-20 reps to fatigue
Increase load 5% once
20 reps achieved
Munro
(2009)
Treadmill, cycle,
resistance training
2 months
3/week
Endurance (30 mins, RPE
13-14), resistance (3 sets
10-15 reps to tolerance)
NS
Maury
(2008)
Treadmill, cycle,
multigym, stairs
3 months
3/week
Endurance (Borg 4-6,
SpO2 >90%), resistance
(60% 1RM, 3 sets 8 reps)
NS
Stiebellehner
(1998)
Cycle
6 weeks
3-5/week
60% max HRR
Lactate levels <4.5.M/L
Increase 12 min/week
to 120 mins/week
Ross
(1993)
Treadmill,
arm ergometry
6-8 weeks
3/week
60-70% max pred HR
NS
Guerrero
(2005)
Cycle
3 months
3/week
50% Wmax (10 min)
30% Wmax (5 min)
Increase to 80% Wmax
Wickerson et al. J Heart Lung Transplant 2010
Aerobic training vs. normal daily activity
Stiebellehner et al. Chest 1998
Physical activity in lung transplant recipients
22 stable lung recipients > 1 year post-transplant
compared to healthy controls
Daily steps
• 4977 vs. 8645 steps/day
Daily walking time
• 55 vs. 81 minutes/ day
Other physical activity outcomes
• Reduced daily standing time
• Increased daily sedentary time
• Reduced time spent in moderate intensity
activity
Langer et al. J Heart Lung Transplant 2009
Physical potential after transplant
1996 U.S Transplant Games (6 lung transplant recipients)
Peak VO2
(ml kg min-1)
22.7 +/- 5.6
% age pred
peak Vo2
85.6 +/- 21.2
Painter et al. Transplantation 1997
Challenges for rehabilitation research
and clinical practice
The optimal exercise prescription for lung transplant recipients is not known
? How reversible are the changes to skeletal muscle
? Is there a slower recovery process following lung transplant
? Is the training stimulus adequate to induce improvements in skeletal muscle
and exercise capacity
? What are the cumulative effects on age and length of disuse on recovery
? What is the role for exercise in recipients with a complicated post-operative
course, multiple and serious comorbidities and marginal organ function
? What is the role for exercise in long-term outcomes
(survival, chronic rejection, CV risk factors)
What is the current clinical practice
of exercise training in Canadian lung
transplant programs?
Lung transplant rehabilitation programs in Canada
Survey sent to 6 different Canadian sites performing lung transplants
 4/6 sites responded
 All recommended rehabilitation pre-transplant
 All had mandatory rehabilitation post-transplant
Lung transplant exercise programs
Exercise Prescription
Frequency
2-3/week for
6-12 weeks or
individual
need
Intensity
•
•
•
•
•
•
•
•
Post-op
restrictions
individualized
assessment
RM
Borg (leg
fatigue)
RPE
target HR
medical
stability
patient
tolerance
Duration
60-120
minutes
•
•
•
•
Mode
Progression
Treadmill
Cycle
Resistance
training
(upper and
lower
extremities)
flexibility
•
•
•
•
•
•
•
Individual
assessment
RPE
target HR
Borg
weekly
progression
of time
patient
tolerance
RM
Outcome
measures
•
•
•
•
•
Borg
6MWT
TUG
Manual
muscle testing
Dynamometry
Future directions
 More studies needed to assess effect of exercise training


Different intensities, durations, modes, progression
Specific training strategies (endurance, resistance training)
 Different groups of recipients



Complicated course
Multiple comorbidities
Older
 Role of prehabilitation in lung transplant candidates
 Role of early mobility during peri-operative period
 Physical activity counselling (long-term)
ACKNOWLEDGEMENTS
Dina Brooks PhD, University of Toronto
Sunita Mathur PhD, University of Toronto
Lianne Singer MD, Toronto General Hospital
Denise Helm BScPT, Toronto General Hospital
Physical Therapy MScPT Program, University of Toronto
Funding sources:
Ontario Respiratory Care Society
Canadian Respiratory Health Professionals