exercise training after lung transplant
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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. - PowerPoint PPT PresentationTRANSCRIPT
Lisa Wickerson BSc PT, MSc(c)Lung Transplant ProgramToronto General Hospital
Canadian Respiratory ConferenceApril 28-30,2011
Exercise training after lung transplant
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 functionObstructive lung disease (FEV1 < 25%pred)Restrictive lung disease ( VC and TLC < 65%pred)Septic lung disease (FEV1 < 30%pred)
Maximal exercise capacitySevere limitation (VO2 peak 20-32%pred)Ventilatory limitation present
Functional exercise capacity6-minute walk test < 400mVascular lung disease (NYHA functional classes III-IV) OtherResting hypoxemia/ oxygen dependencyVery low physical functioning subscales on HRQOL questionnaires (i.e. SF 36)
Lung function after lung transplant
Single Lung transplant(SLTx)
Double Lung transplant(DLTx)
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
• 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
Physiological limitations to maximal exercise
Exercise limitation
Ventilatory Peripheral Cardiac/ vascular
-Adequate HR, SV-Mild anemia-Decreased RVF in SLTx with PHTN
- Adequate ventilation- Adequate gas exchange- Mild defects in SLTx
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
Non-invasive
31P-MRS
NIRS
MRI
• Low resting muscle pH• Earlier drop in intracellular pH with exercise
• Smaller drop in hemoglobin and myoglobin oxygen saturation during exercise
• Decreased muscle volume • Increased intramuscular fat infiltration
Computerized dynamometry
• Decreased peak torque• Decreased isometric endurance
Evans et al, 1997, Mathur et al, 2008, Tirdel et al, 1998, Wang et al, 1999, McKenna et al, 2003
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 diseaseDecreased muscle mass (cross-sectional area)Decreased muscle strength and enduranceIncreased 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 factorsChronic 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
Pre-LTXPre-LTX Post-LTXPost-LTX Post Post
RehabilitationRehabilitation
BMI kg/m2 22.7 ± 4.2 21.7 ± 4.2 23.1 ± 3.7FEV1 L 0.85 ± 0.47 1.96 ± 0.85* 2.20 ± 0.99*
% pred 31 ± 15 70 ± 21* 78 ± 25*6MWD m 311 ± 124 320 ± 138 449 ± 128*,†
% pred 45 ± 19 46 ± 19 65 ± 17*,†
QF % pred 72 ± 30 51 ± 28* 59 ± 26*,†
*p < 0.05 vs. pre-LTX. †p < 0.05 vs. post-LTX.
Maury et al. Am J Transplant 2008
A cohort study of 36 lung transplant recipients (15 SLTx, 21 DLTx)
Post-transplant peripheral muscle dysfunction
Maury et al. Am J Transplant 2008
•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
Exercise limitation post organ transplantation
Similar exercise profiles seen in heart, kidney and liver transplant recipientsDecreased VO2peak
Early anaerobic thresholdAbsence of circulatory or ventilatory limitation
Common to all organ transplantsPre-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
Wickerson et al. J Heart Lung Transplant 2010
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
6MWDFEV1, FVCSF 36
Increase in 6MWD, FEV1 and FVC, HRQOL
Maury (2008)
Prospective cohort
36 Aerobic & resistance exercise
6MWDQF, HGFFEV1
Increase in 6MWD, QF, HGF
Stiebellehner(1998)
Prospective cohort
9 Aerobic exercise VO2 peak
Peak power outputIncrease 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
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 HRRLactate 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% WmaxWickerson et al. J Heart Lung Transplant
2010
Physical activity in lung transplant recipients
Langer et al. J Heart Lung Transplant 2009
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
Physical potential after transplant
1996 U.S Transplant Games (6 lung transplant recipients)
Peak VO2 22.7 +/- 5.6(ml kg min-1)
% age pred 85.6 +/- 21.2peak Vo2
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)
Lung transplant rehabilitation programs in Canada
Survey sent to 6 different Canadian sites performing lung transplants4/6 sites respondedAll recommended rehabilitation pre-transplantAll had mandatory rehabilitation post-transplant
Lung transplant exercise programs
Exercise Prescription Outcome measuresFrequenc
yIntensity Duration Mode Progressio
n2-3/week for6-12 weeks or individual need
• Post-op restrictions
• individualized assessment
• RM• Borg (leg
fatigue)• RPE• target HR• medical
stability• patient
tolerance
60-120 minutes
• Treadmill• Cycle• Resistanc
e training (upper and lower extremities)
• flexibility
• Individual assessment
• RPE• target HR• Borg• weekly
progression of time
• patient tolerance
• RM
• 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 TorontoSunita Mathur PhD, University of TorontoLianne Singer MD, Toronto General HospitalDenise Helm BScPT, Toronto General HospitalPhysical Therapy MScPT Program, University of Toronto
Funding sources:Ontario Respiratory Care SocietyCanadian Respiratory Health Professionals