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Exercise training after lung transplant

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Presentation on theme: "Exercise training after lung transplant"— Presentation transcript:

1 Exercise training after lung transplant
Lisa Wickerson BSc PT, MSc(c) Lung Transplant Program Toronto General Hospital Canadian Respiratory Conference April 28-30,2011

2 Disclosure of potential conflicts of interest
None to declare

3 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

4 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 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

5 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)

6 Lung function after lung transplant
Single Lung transplant (SLTx) Double Lung transplant (DLTx) COPD Obstructive defect (FEV %) 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

7 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

8 What is the nature of exercise limitation in lung transplant recipients?

9 Physiological limitations to maximal exercise
Exercise limitation Ventilatory Peripheral Cardiac/ vascular - Adequate ventilation - Adequate gas exchange - Mild defects in SLTx Abnormal oxidative capacity of skeletal muscles Impaired oxygen uptake Impaired oxygen utilization Intrinsic abnormalities -Adequate HR, SV -Mild anemia -Decreased RVF in SLTx with PHTN

10 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

11 When does peripheral muscle function deteriorate in lung transplant recipients?

12 Post-transplant peripheral muscle dysfunction
Pre-operative factors Post-operative factors Peri-operative factors

13 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

14 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)

15 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

16 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

17 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 Rejection (acute, chronic) Medications (calcineurin inhibitors, corticosteroids) Decreased physical activity

18 Post-transplant peripheral muscle dysfunction
A cohort study of 36 lung transplant recipients (15 SLTx, 21 DLTx) Pre-LTX Post-LTX Post Rehabilitation BMI kg/m ± ± ± 3.7 FEV1 L 0.85 ± ± 0.85* 2.20 ± 0.99* % pred ± ± 21* ± 25* 6MWD m 311 ± ± ± 128*,† % pred ± ± ± 17*,† QF % pred ± ± 28* ± 26*,† *p < 0.05 vs. pre-LTX. †p < 0.05 vs. post-LTX. Maury et al. Am J Transplant 2008

19 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

20 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)

21 To what extent can exercise training improve exercise capacity and peripheral muscle function in lung transplant recipients?

22 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) 16 Lumbar resistance exercises -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) Aerobic & resistance exercise QF, HGF FEV1 Increase in 6MWD, QF, HGF Stiebellehner (1998) 9 Aerobic exercise VO2 peak Peak power output Increase in VO2 peak and peak workload Ross (1993) 8 VO2max Hemo-dynamic responses Increased VO2max and work rate Guerrero (2005) Controlled trial (healthy controls) 12 Mitochondrial respiration Significant increase in bioenergetics at cellular level, Wmax , endurance time Wickerson et al. J Heart Lung Transplant 2010

23 Exercise prescriptions
Study Mode Duration Frequency Intensity Progression Braith (2007) Lumbar extension training 6 months 1/week 1 set reps to fatigue Increase load 5% once 12 reps achieved Mitchell (2003) 1 set 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 reps to tolerance) NS Maury (2008) Treadmill, cycle, multigym, stairs 3 months Endurance (Borg 4-6, SpO2 >90%), resistance (60% 1RM, 3 sets 8 reps) 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 60-70% max pred HR Guerrero (2005) 50% Wmax (10 min) 30% Wmax (5 min) Increase to 80% Wmax Wickerson et al. J Heart Lung Transplant 2010

24 Aerobic training vs. normal daily activity
Stiebellehner et al. Chest 1998

25 Physical activity in lung transplant recipients
22 stable lung recipients > 1 year post-transplant compared to healthy controls Daily steps 4977 vs 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

26 Physical potential after transplant
1996 U.S Transplant Games (6 lung transplant recipients) Peak VO /- 5.6 (ml kg min-1) % age pred / peak Vo2 Painter et al. Transplantation 1997

27 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)

28 What is the current clinical practice of exercise training in Canadian lung transplant programs?

29 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

30 Lung transplant exercise programs
Exercise Prescription Outcome measures Frequency Intensity Duration Mode Progression 2-3/week for 6-12 weeks or individual need Post-op restrictions individualized assessment RM Borg (leg fatigue) RPE target HR medical stability patient tolerance minutes Treadmill Cycle Resistance training (upper and lower extremities) flexibility Individual assessment Borg weekly progression of time 6MWT TUG Manual muscle testing Dynamometry

31 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)

32 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

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