Presentation on theme: "Exercise training after lung transplant"— Presentation transcript:
1 Exercise training after lung transplant Lisa Wickerson BSc PT, MSc(c)Lung Transplant ProgramToronto General HospitalCanadian Respiratory ConferenceApril 28-30,2011
2 Disclosure of potential conflicts of interest None to declare
3 Learning objectivesDescribe the physiological limitations to exercise in lung transplant recipientsIdentify the evidence for exercise training in improving functional outcomes following lung transplantationRecognize the specific components and structure of exercise training programs in lung transplant centres across Canada
4 Lung transplantationEstablished 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 between180 lung transplants performed in 6 Canadian transplant programs in 2010Goals of transplant:Decrease disabling symptomsImprove functional capacityImprove health-related quality of lifeIncrease life expectancyCIHI Canadian Organ Replacement Register 2011
5 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 presentFunctional exercise capacity6-minute walk test < 400mVascular lung disease (NYHA functional classes III-IV)OtherResting hypoxemia/ oxygen dependencyVery low physical functioning subscales on HRQOLquestionnaires (i.e. SF 36)
6 Lung function after lung transplant Single Lung transplant(SLTx)Double Lung transplant(DLTx)COPDObstructive defect (FEV %)Restrictive lung diseaseRestrictive defect (FEV1 80%)Moderately decreased DLCO (62%)Mild desaturation on exertionPulmonary HypertensionDecreased DLCOVery mild restrictionUsually no further improvement after 6 monthsMild restrictionMild decrease DLCONo 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 transplantWilliams 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 limitationVentilatory PeripheralCardiac/ vascular- Adequate ventilation- Adequate gas exchange- Mild defects in SLTxAbnormal oxidative capacity of skeletal musclesImpaired oxygen uptakeImpaired oxygen utilizationIntrinsic abnormalities-Adequate HR, SV-Mild anemia-Decreased RVF in SLTx with PHTN
10 Peripheral muscle function MeasuresFindingsMuscle biopsiesLower proportion of Type 1 muscle fibresLow mitochondrial oxidative enzyme activityHigher glycolytic enzyme activityLow ATP production rateArterial blood samplingAbnormal potassium regulationNon-invasive31P-MRSNIRSMRILow resting muscle pHEarlier drop in intracellular pH with exerciseSmaller drop in hemoglobin and myoglobin oxygen saturation during exerciseDecreased muscle volumeIncreased intramuscular fat infiltrationComputerized dynamometryDecreased peak torqueDecreased isometric enduranceEvans 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?
13 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 metabolismDecreased proportion of type 1 fibresDecreased muscle capillarityEarly onset lactic acidosisDecreased concentration of oxidative enzymesATS/ERS Am J Respir Crit Care Med 1999
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 controlsSimilar muscle mass, composition and strength between groupsQuadriceps endurance tended to be lower in lung transplant recipientsMathur et al. Cardiopulm Phys Ther J 2008
17 Post-transplant peripheral muscle dysfunction Peri-operative issuesIschemic injuryAllograft qualityProtein catabolism (response to sepsis)Critical illness myopathy / use of neuromuscular blocking agentsSystemic organ dysfunctionImmobilization / prolonged hospitalizationNutritional statusInfectionRejectionPost-operative/ long term issuesRejection (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 PostRehabilitationBMI kg/m ± ± ± 3.7FEV1 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 forceLinear regression analysis suggest a decline of 0.8Nm of quadriceps force/dayMaury et al. Am J Transplant 2008
20 Exercise limitation post organ transplantation Similar exercise profiles seen in heart, kidney and liver transplant recipientsDecreased VO2peakEarly anaerobic thresholdAbsence of circulatory or ventilatory limitationCommon to all organ transplantsPre-transplantDeconditioningCentral limitations to exerciseMonths to years of chronic diseasePost-transplantProlonged hospital stayImmunosuppression 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 2010AuthorStudy DesignSample SizeInterventionsOutcome MeasuresSignificant FindingsBraith(2007)RCT30Alendronate and lumbar resistance exercisesLumbar BMD-BMD 14.1± 3.9% below baseline (controls)-BMD 10.8±2.3% above baseline (alendronate + resistance)Mitchell(2003)16Lumbar resistanceexercises-BMD 19.5% below baseline (controls)-BMD 5 % below baseline (intervention)Munro(2009)Prospective cohort36Aerobic & resistance exercise6MWDFEV1, FVCSF 36Increase in 6MWD, FEV1 and FVC, HRQOLMaury(2008)Aerobic & resistanceexerciseQF, HGFFEV1Increase in 6MWD, QF, HGFStiebellehner(1998)9Aerobic exerciseVO2 peakPeak power outputIncrease in VO2 peak and peak workloadRoss(1993)8VO2maxHemo-dynamic responsesIncreased VO2max and work rateGuerrero(2005)Controlled trial (healthy controls)12Mitochondrial respirationSignificant increase in bioenergetics at cellular level, Wmax , endurance timeWickerson et al. J Heart Lung Transplant 2010
23 Exercise prescriptions StudyModeDurationFrequencyIntensityProgressionBraith(2007)Lumbar extension training6 months1/week1 set reps to fatigueIncrease load 5% once 12 reps achievedMitchell(2003)1 set reps to fatigueIncrease load 5% once 20 reps achievedMunro(2009)Treadmill, cycle, resistance training2 months3/weekEndurance (30 mins, RPE 13-14), resistance (3 sets reps to tolerance)NSMaury(2008)Treadmill, cycle, multigym, stairs3 monthsEndurance (Borg 4-6, SpO2 >90%), resistance (60% 1RM, 3 sets 8 reps)Stiebellehner(1998)Cycle6 weeks3-5/week60% max HRRLactate levels <4.5.M/LIncrease 12 min/week to 120 mins/weekRoss(1993)Treadmill, arm ergometry6-8 weeks60-70% max pred HRGuerrero(2005)50% Wmax (10 min)30% Wmax (5 min)Increase to 80% WmaxWickerson 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 controlsDaily steps4977 vs steps/dayDaily walking time55 vs. 81 minutes/ dayOther physical activity outcomesReduced daily standing timeIncreased daily sedentary timeReduced time spent in moderate intensity activityLanger 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 Vo2Painter 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 muscleand 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-operativecourse, 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 transplants4/6 sites respondedAll recommended rehabilitation pre-transplantAll had mandatory rehabilitation post-transplant
30 Lung transplant exercise programs Exercise PrescriptionOutcome measuresFrequencyIntensityDurationModeProgression2-3/week for6-12 weeks or individual needPost-op restrictionsindividualized assessmentRMBorg (leg fatigue)RPEtarget HRmedical stabilitypatient toleranceminutesTreadmillCycleResistance training (upper and lower extremities)flexibilityIndividual assessmentBorgweekly progression of time6MWTTUGManual muscle testingDynamometry
31 Future directionsMore studies needed to assess effect of exercise trainingDifferent intensities, durations, modes, progressionSpecific training strategies (endurance, resistance training)Different groups of recipientsComplicated courseMultiple comorbiditiesOlderRole of prehabilitation in lung transplant candidatesRole of early mobility during peri-operative periodPhysical activity counselling (long-term)
32 ACKNOWLEDGEMENTSDina 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