Presentation on theme: "Lisa Wickerson BSc PT, MSc(c) Lung Transplant Program Toronto General Hospital Canadian Respiratory Conference April 28-30,2011 Exercise training after."— Presentation transcript:
Lisa Wickerson BSc PT, MSc(c) Lung Transplant Program Toronto General Hospital Canadian Respiratory Conference April 28-30,2011 Exercise training after lung transplant
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 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 (FEV 1 < 25% pred ) Restrictive lung disease ( VC and TLC < 65% pred ) Septic lung disease (FEV 1 < 30% pred ) Maximal exercise capacity Severe limitation (VO 2 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) Double Lung transplant (DLTx) COPD Obstructive defect (FEV %) Restrictive lung disease Restrictive defect (FEV 1 80%) Moderately decreased D LCO (62%) Mild desaturation on exertion Pulmonary Hypertension Decreased D LCO Very mild restriction Usually no further improvement after 6 months Mild restriction Mild decrease D LCO 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 (VO 2peak 40-60% predicted) Low peak work rate (W peak < 40% predicted) Early anaerobic threshold (30% of VO 2 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 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 MeasuresFindings 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
When does peripheral muscle function deteriorate in lung transplant recipients?
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-LTXPost-LTX Post Pre-LTXPost-LTX PostRehabilitation BMIkg/m ± ± ± 3.7 FEV 1 L0.85 ± ± 0.85*2.20 ± 0.99* % pred 31 ± ± 21* 78 ± 25* 6MWDm 311 ± ± ± 128*, † % pred 45 ± ± ± 17*, † QF% pred 72 ± ± 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 recipients Decreased VO 2peak 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 Wickerson et al. J Heart Lung Transplant 2010 AuthorStudy Design Sample Size InterventionsOutcome Measures Significant Findings Braith (2007) RCT30Alendronate 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) RCT16Lumbar resistance exercises Lumbar BMD-BMD 19.5% below baseline (controls) -BMD 5 % below baseline (intervention) Munro (2009) Prospective cohort 36Aerobic & resistance exercise 6MWD FEV 1, FVC SF 36 Increase in 6MWD, FEV 1 and FVC, HRQOL Maury (2008) Prospective cohort 36Aerobic & resistance exercise 6MWD QF, HGF FEV 1 Increase in 6MWD, QF, HGF Stiebellehner (1998) Prospective cohort 9Aerobic exerciseVO 2 peak Peak power output Increase in VO 2 peak and peak workload Ross (1993) Prospective cohort 8Aerobic exerciseVO 2max Hemo-dynamic responses Increased VO 2max and work rate Guerrero (2005) Controlled trial (healthy controls) 12Aerobic exerciseMitochondrial respiration Significant increase in bioenergetics at cellular level, W max, endurance time Wickerson et al. J Heart Lung Transplant 2010
Exercise prescriptions StudyModeDurationFrequencyIntensityProgression Braith (2007) Lumbar extension training 6 months1/week1 set reps to fatigueIncrease load 5% once 12 reps achieved Mitchell (2003) Lumbar extension training 6 months1/week1 set reps to fatigueIncrease load 5% once 20 reps achieved Munro (2009) Treadmill, cycle, resistance training 2 months3/weekEndurance (30 mins, RPE 13-14), resistance (3 sets reps to tolerance) NS Maury (2008) Treadmill, cycle, multigym, stairs 3 months3/weekEndurance (Borg 4-6, SpO 2 >90%), resistance (60% 1RM, 3 sets 8 reps) NS Stiebellehner (1998) Cycle6 weeks3-5/week60% max HRR Lactate levels <4.5.M/L Increase 12 min/week to 120 mins/week Ross (1993) Treadmill, arm ergometry 6-8 weeks3/week60-70% max pred HRNS Guerrero (2005) Cycle3 months3/week50% W max (10 min) 30% W max (5 min) Increase to 80% W max 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 Langer et al. J Heart Lung Transplant 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
Physical potential after transplant 1996 U.S Transplant Games (6 lung transplant recipients) Peak VO /- 5.6 (ml kg min-1) % age pred85.6 +/ peak 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)
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 PrescriptionOutcome measures FrequencyIntensityDurationModeProgression 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 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 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