Tania Janaudis-Ferreira, BSc(PT), MSc, PhD

Associate Professor, School of Physical and Occupational Therapy, McGill University

Scientist, Translational Research in Respiratory Diseases Program, Research Institute, McGill University Health Centre 

Associate Member, Faculty of Medicine, Respiratory Division, McGill University

Lung transplantation provides individuals with end stage lung disease a second chance of life and the opportunity to regain physical function and improve their health-related quality of life (HRQL).¹ However, these individuals continue to experience challenges post-transplant such as impaired mobility and exercise capacity, reduced muscle strength and low levels of physical activity.² Studies have shown that decreased physical function and exercise capacity in lung transplant candidates and recipients are associated with poorer clinical outcomes, increased healthcare utilization and mortality.³

Post transplant rehabilitation aims to help transplant recipients recover early post-transplant and improve exercise capacity, muscle strength, HRQL, as well as outcomes related to cardiovascular disease long-term post-transplant.² This article provides an overview of the evidence for rehabilitation post lung transplantation.

Rehabilitation post-transplant

A 2021 Cochrane review on exercise training for adult lung transplant recipients included eight RCTs (438 participants).⁴ The authors did not perform meta-analyses due to the heterogeneity of the intervention and outcomes, and uncertainty of some of the data. The overall risk of bias of the included studies was considered high.⁴ Three studies looked at the effects of resistance training, with variations in comparators, e.g., two different resistance trainings, supervised versus unsupervised upper limb programs and exercises on a vibratory platform versus the same exercises on the floor.^5,6,7 Another study compared different durations of multimodal exercise programs,⁸ while two studies compared multimodal training to usual care or no exercise.^9,10 Additionally, two studies examined resistance training focused on lumbar strength,^11,12 including one where resistance training was combined with alendronate (used for the fixation of calcium in people with osteoporosis or who consumed immunosuppressants), compared to alendronate alone or usual care.¹²

Although some studies showed improvements in maximal and functional exercise capacity, as well as in health-related quality of life (HRQL),⁴ the overall evidence remains uncertain. It is also unclear whether post-transplant exercise training improves muscle strength, given that different muscle groups were evaluated and at various time points.⁴ Pulmonary function was evaluated in three studies and the authors reported no difference in FEV1, FVC or DLCO after exercise.⁴ Two studies evaluated acute graft rejection and reported no significant differences between the intervention and control groups for acute graft rejection episodes 6 months after the exercise training.^11,12 Adverse events, patient readmission to hospital and death were rarely reported and return to normal activities was not reported at all.⁴ 

It's evident that new high-quality RCTs with larger sample sizes are needed to strengthen the evidence in this field. However, it is not only improved methodology that is required; strategic research questions also need to be formulated, as many remain unanswered. For instance, what is the optimal timing for initiating post-transplant rehabilitation (early vs. late)? Depending on the post-transplant phase, the goals and types of exercises may vary; early post-transplant focuses on recovery, while late post-transplant aims to improve physical fitness to manage conditions such as new-onset hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome. The 2021 Cochrane review⁴ was unable to conduct a meta-analysis partly due to heterogeneity in outcome measures. To advance the field, future trials need to use common outcomes to facilitate comparison among studies and enable meta-analysis. Fortunately, researchers have begun working on identifying core outcome domains for clinical trials in physical rehabilitation following transplantation.¹³ It is also important to point out that the studies included in the Cochrane review⁴ considered patients with a non-complicated course post-transplant; complex post-surgical state have not been explored in RCTs. Another important question that remains unclear is whether exercise training influences immune function of lung transplant recipients that could impact organ rejection (either negatively or positively).

Although evidence on the effects of exercise training programs for transplant recipients, as well as the optimal exercise plans, is limited, this intervention is currently recognized as essential in the management of lung transplant patients.^2,14 In some countries, pre- and post-transplant rehabilitation is mandatory at most lung transplant centers.¹⁵ Stronger evidence in this field could inform practice guidelines regarding the optimal training regimes for specific patient populations (e.g., those with complicated versus non-complicated courses) and the timing post-transplant. This would help optimize existing programs, direct resources, and support the implementation of these interventions at centers where rehabilitation is not currently offered to lung transplant recipients.

References

1. Leard EL, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: an update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021; 40(11):1349-1379.
2. Janaudis-Ferreira T, Mathur S, Deliva R, et al. Exercise for Solid Organ Transplant Candidates and Recipients: A Joint Position Statement of the Canadian Society of Transplantation and CAN-RESTORE. Transplantation. 2019;103(9):e220-e38.
3. Bourgeois N, Shallwani SM, Al-Huda FS, et al. Relationship of Exercise Capacity, Physical Function, and Frailty Measures With Clinical Outcomes and Healthcare Utilization in Lung Transplantation: A Scoping Review. Transplantation Direct. 2022;8(11):e1385.
4. Gutierrez-Arias R, Martinez-Zapata MJ, Gaete-Mahn MC, et al. Exercise training for adult lung transplant recipients. Cochrane Database Syst Rev. 2021;7(7):Cd012307.
5. Fuller LM, El-Ansary D, Button BM, et al. Effect of upper limb rehabilitation compared to no upper limb rehabilitation in lung transplant recipients: a randomized controlled trial. Archives of Physical Medicine & Rehabilitation 2018;99(7):1257-64.
6. Gloeckl R, Heinzelmann I, Seeberg S, et al. Effects of complementary whole-body vibration training in patients after lung transplantation: a randomized, controlled trial. Journal of Heart & Lung Transplantation 2015;34(11):1455-61.
7. Gloeckl R, Jarosch I, Seeberg S, et al. Whole body vibration training in long-term (>1 year) lung transplant patients - a randomized, controlled trial [abstract]. European Respiratory Journal 2017;50(Suppl 61).
8. Fuller LM, Button B, Tarrant B, et al. Longer versus shorter duration of supervised rehabilitation after lung transplantation: a randomized trial. Archives of Physical Medicine & Rehabilitation 2017;98(2):220-6.
9. Langer D, Burtin C, Schepers L, et al. Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial. American Journal of Transplantation 2012;12(6):1584-92.
10. Ulvestad M, Durheim MT, Kongerud JS, et al. Effect of high-intensity training on peak oxygen uptake and muscular strength after lung transplantation: a randomized controlled trial. Journal of Heart & Lung Transplantation 2020;39(9):859-67.
11. Mitchell MJ, Baz MA, Fulton MN, et al. Resistance training prevents vertebral osteoporosis in lung transplant recipients. Transplantation 2003;76(3):557-62.
12. Braith RW, Conner JA, Fulton MN, et al. Comparison of alendronate vs alendronate plus mechanical loading as prophylaxis for osteoporosis in lung transplant recipients: a pilot study. Journal of Heart & Lung Transplantation 2007;26(2):132-7.
13. Santana Shiguemoto T, Janaudis-Ferreira T, et al. Identifying outcome domains for clinical trials of physical rehabilitation among adults undergoing solid organ transplantation using a delphi approach. Progress in Transplantation. 2023; 33(1): 50-60.
14. Spruit MA, Singh S, Garvey C et al. Official American Thoracic Society/European
    Respiratory Society Statement: Key Concepts and Advances in Pulmonary Rehabilitation. Am J Respir Crit Care Med. 2013; Vol 188, Iss. 8, pp e13–e64.

15.Trojetto T, Elliot RJ, Rashid. S et al. Availability, characteristics, and barriers of rehabilitation programs in organ transplant populations across Canada. Clinical Transplantation. 2011; 25(6):E571-8.