Key words : Exercise capacity, Lung transplantation, Physiotherapy, Pulmonary rehabilitation, Rehabilitative intervention

Introduction

Lung transplant (LTx) is an excellent therapeutic option for patients with advanced/end-stage diseases such as idiopathic pulmonary fibrosis, cystic fibrosis, end-stage septic lung disease, and pulmonary hypertension.^1-5 The expected benefits after LTx are the increased rate of patient survival and improved quality of life,⁶ as quality of life is particularly reduced in patients with end-stage lung diseases.⁷ In addition, long-term pharmacological treatment with corticosteroids can result in muscle atrophy and consequent peripheral muscle dysfunc-tion affecting the limbs.⁸ Meanwhile, inactivity and deconditioning represent additional negative factors that influence exercise capacity and physical function in patients with lung disease. Although respiratory function can improve after LTx, the negative effects of the chronic underlying disease may continue, mostly in the musculoskeletal and cardiopulmonary systems.⁹

Preoperative rehabilitation can contribute to enhancing exercise capacity, reducing dyspnea, and improving muscle strength and thereby positively influence patients’ quality of life^10,11 and facilitate favorable physical and psychological conditioning for patients before surgery.¹² Enhancing muscle strength aerobic capacity preoperatively also allows patients to become accustomed to exercise, especially considering that the waiting time on the active list can vary.¹³

In a previously published review that investigated the possible effects of preoperative rehabilitation in patients with idiopathic pulmonary fibrosis who were candidates for LTx, it was not possible to demonstrate the effectiveness of preoperative rehabilitation, because of the absence of comparative studies of LTx candidates who did or did not attend preoperative rehabilitation.¹⁴

The purpose of this review was to define whether preoperative rehabilitation influences the quality of life in patients who are candidates for LTx.

Materials and Methods

This was a scoping review,¹⁵ conducted by searching 4 primary databases, namely, PubMed, Scopus, Cochrane Library, and Web of Science.

Search strategy
Databases were searched from inception to January 2022. Three keyword entries, “lung transplantation,” “preoperative rehabilitation,” and “quality of life,” were matched using the Boolean operator AND. In each database the following fields were searched: PubMed (all fields), Scopus (title, abstract, keywords), Cochrane Library (title, abstract, keywords), and Web of Science (topic). Filters were applied for age (adult only) and language (English only). No filters were applied for gender, publication date, and subject. The search process was completed in January 2022.

Inclusion and exclusion criteria
To be included, citations were required to be published in English and to describe preoperative rehabilitation in patients waiting for LTx. For the purpose of this review, we sought to include randomized controlled trials, observational studies, and case reports. All citations that lacked descriptions of preoperative rehabilitation in patients waiting for LTx and/or were published in languages other than English were not eligible for inclusion. Abstracts, conference proceedings, editorials, letters to editor, and study protocols were also not eligible for inclusion.

Selection process
From the retrieved citations, duplicates were removed, and the remaining documents were screened for eligibility according to the content of the abstracts. Subsequently, for those documents with abstracts that met the inclusion criteria, the full text of each article was also screened for the inclusion criteria, and confirmed articles were considered eligible for the final analysis. We followed the PRISMA Guidelines16 for this review. The studies gathered from the literature by these methods were further evaluated through an open, standardized process by 3 independent reviewers who had evaluated and agreed on the results.

Results

From the searched databases, we retrieved 57 citations. After removal of duplicates, 41 documents were screened for eligibility. Two articles were included in the final analysis, as shown in Figure 1. One study was a systematic review,¹⁷ and the other was an observational prospective study.¹¹ There were 1344 patients, of whom 48% were men, that constituted the cohort of the included studies. The systematic review included 6 studies that evaluated the correlation between preoperative rehabilitation and quality of life in LTx candidates.¹⁷

The rehabilitative interventions were mainly focused on motor and breathing exercises and were integrated by education programs, as shown in Table 1. Preoperative rehabilitation was shown to be effective at improving quality of life and mood status and reducing dyspnea in patients waiting for LTx. The 36-Item Short Form Health Survey developed for the RAND Medical Outcomes Study, the EuroQuol EQ-5D health-value descriptive system, the St. George’s Respiratory Questionnaire, the Quality of Well-being Scale, the modified Medical Research Council Dyspnea Scale, and the Beck Depression Inventory were the questionnaires and evaluation tools that were used among the included studies. In addition, the 6-minute walking distance increased after patients participated in preoperative rehabilitative programs, as shown in Table 1. Preoperative rehabili-tation was composed of different types of exercise with variable duration. Aerobic exercise (ergometer or treadmill), muscle strengthening exercises (arms and legs), endurance training, and breathing exercises were the most commonly described techniques.

In addition, stretching (arms, legs, hips muscles), education, and Nordic walking constituted other components of the preoperative programs (Table 1). Duration of programs varied from 3 to 20 weeks, and frequency varied from 3 times per week to as often as 5 to 6 times per week.^11,17

Discussion

The aim of the present review was to define whether preoperative rehabilitation can influence the quality of life in patients waiting for LTx. This is an interesting and, as we have found here, infrequently covered topic. In fact, only a few studies have investigated the effects of preoperative rehabilitation in LTx recipients.^10,11,17-22 Review of the studies showed that duration, type, and frequency of preoperative rehabilitation varied, and it was provided in an outpatient setting, including preoperative programs at home.

In this regard, the worldwide COVID-19 pan-demic has forced patients to stay home and perhaps reduced the possibilities to attend preoperative rehabilitation. Subsequently, home-based rehabili-tation has attracted greater interest, and initial experiences are providing encouraging data.²³ A study conducted among 23 patients (mostly male) waiting for LTx found that an 8-week mixed preoperative rehabilitation program (that included home-based exercises) was effective at reducing dyspnea perception after 8 weeks (P < .001).²⁴ More specifically, another study conducted among 78 patients (mostly male) provided the basis for further development of telerehabilitation in LTx candidates.²⁵ An 8-week telerehabilitation program has also been found to be feasible and safe for LTx recipients.²⁶ Differences that characterize preoperative rehabilitation programs have been discussed elsewhere, and it is commonly accepted that, in response to the lack of novel guidelines for optimal exercise plans for LTx candidates, preoperative rehabilitation should be provided in accordance with the established recommendations generally associated with outpatient programs.²⁷ Mobility is crucial, because ambulatory capacity and physical activity are prerequisites for lung transplant/retransplant eligibility.²⁸

Multidisciplinarity in lung transplant
The first successful LTx procedures date back to the 1980s with the pioneering experiences at the Toronto Lung Transplant Centre.29,30 Review of the early history of the LTx field shows that transplant surgeons did, in fact, recognize the importance of both preoperative and postoperative rehabilitation to facilitate optimal preoperative conditions for patients and to expedite postoperative recovery.^30-32

More importantly, during the complex pathway that begins at patient selection and placement on active wait lists, multidisciplinarity is a cornerstone.³³ Optimal surgical outcomes require support from many disciplines, and our predecessors recognized this notion early in our history and understood the importance of such a complex and multifaceted procedure, particularly with regard to rehabilitation.^29,32 Furthermore, multidisciplinarity can be today enhanced by international cooperation among centers and stimulated even in those developing countries that are starting LTx programs where preoperative rehabilitation is not available because of its related costs.³⁴ Patients receiving LTx are expecting to restore their quality of life, and some can even get involved in sports activities or adventurous travels safely.^35,36

Limitations
Although the search was conducted among a substantial number of databases, a primary limitation of the present study was the small number of citations included in the final analysis. Despite this constraint, we are confident that the information we have retrieved would not be enhanced by extending our searches to include additional databases.

Another primary limitation was the hetero-geneous nature of the treatments provided to LTx candidates during preoperative rehabilitation. Despite this variability, our primary scope was to understand whether preoperative rehabilitation can influence the quality of life in patients waiting for LTx. The results we have presented in this review have allowed us to respond to our research question positively.

Conclusions

Although preoperative rehabilitation for patients waiting for LTx is commonly recognized as a crucial intervention to promote active mobility and preserve both motor and respiratory functions, this topic is not covered extensively in the literature. With the present review, we found that preoperative rehabilitation programs include patient education, and these programs are primarily focused on motor and respiratory exercises. Patients waiting on active list for LTx should be encouraged to attend preoperative rehabilitation in order to preserve and improve their quality of life. Contextually, LTx centers that are not prepared yet to provide preoperative rehabilitation should deserve more attention to this specific rehabilitative treatment because patients arriving at transplantation in better conditions are most likely to succeed postoperatively.

References:

1. Corris PA. Lung transplantation for cystic fibrosis and bronchiectasis. Semin Respir Crit Care Med. 2013;34(3):297-304. doi:10.1055/s-0033-1348469
   CrossRef - PubMed
   
2. Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev. 2021;30(161):210017. doi:10.1183/16000617.0017-2021
   CrossRef - PubMed
   
3. Lordan JL, Corris PA. Pulmonary arterial hypertension and lung transplantation. Expert Rev Respir Med. 2011;5(3):441-454. doi:10.1586/ers.11.21
   CrossRef - PubMed
   
4. Rao JN, Forty J, Hasan A, et al. Bilateral lung transplant: the procedure of choice for end-stage septic lung disease. Transplant Proc. 2001;33(1-2):1622-1623. doi:10.1016/s0041-1345(00)02617-8
   CrossRef - PubMed
   
5. Yeung JC, Keshavjee S. Overview of clinical lung transplantation. Cold Spring Harb Perspect Med. 2014;4(1):a015628. doi:10.1101/cshperspect.a015628
   CrossRef - PubMed
   
6. Singer JP, Singer LG. Quality of life in lung transplantation. Semin Respir Crit Care Med. 2013;34(3):421-430. doi:10.1055/s-0033-1348470
   CrossRef - PubMed
   
7. Langer D. Rehabilitation in patients before and after lung transplantation. Respiration. 2015;89(5):353-362. doi:10.1159/000430451
   CrossRef - PubMed
   
8. Schakman O, Gilson H, Thissen JP. Mechanisms of glucocorticoid-induced myopathy. J Endocrinol. 2008;197(1):1-10. doi:10.1677/JOE-07-0606
   CrossRef - PubMed
   
9. Thomsen D, Jensen BO. Patients’ experiences of everyday life after lung transplantation. J Clin Nurs. 2009;18(24):3472-3479. doi:10.1111/j.1365-2702.2009.02828.x
   CrossRef - PubMed
   
10. Florian J, Rubin A, Mattiello R, Fontoura FF, Camargo Jde J, Teixeira PJ. Impact of pulmonary rehabilitation on quality of life and functional capacity in patients on waiting lists for lung transplantation. J Bras Pneumol. 2013;39(3):349-356. doi:10.1590/S1806-37132013000300012
    CrossRef - PubMed
    
11. Pehlivan E, Balci A, Kilic L, Kadakal F. Preoperative pulmonary rehabilitation for lung transplant: effects on pulmonary function, exercise capacity, and quality of life; first results in Turkey. Exp Clin Transplant. 2018;16(4):455-460. doi:10.6002/ect.2017.0042
    CrossRef - PubMed
    
12. Craven JL, Bright J, Dear CL. Psychiatric, psychosocial, and rehabilitative aspects of lung transplantation. Clin Chest Med. 1990;11(2):247-257.
    CrossRef - PubMed
    
13. Kourliouros A, Hogg R, Mehew J, et al. Patient outcomes from time of listing for lung transplantation in the UK: are there disease-specific differences? Thorax. 2019;74(1):60-68. doi:10.1136/thoraxjnl-2018-211731
    CrossRef - PubMed
    
14. Polastri M, Dell’Amore A, Zagnoni G, Nava S. Preoperative physiotherapy in subjects with idiopathic pulmonary fibrosis qualified for lung transplantation: implications on hospital length of stay and clinical outcomes. J Thorac Dis. 2016;8(5):E264-E268. doi:10.21037/jtd.2016.03.52
    CrossRef - PubMed
    
15. Sucharew H, Macaluso M. Progress notes: methods for research evidence synthesis: the scoping review approach. J Hosp Med. 2019;14(7):416-418. doi:10.12788/jhm.3248
    CrossRef - PubMed
    
16. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906. doi:10.1016/j.ijsu.2021.105906
    CrossRef - PubMed
    
17. Hoffman M, Chaves G, Ribeiro-Samora GA, Britto RR, Parreira VF. Effects of pulmonary rehabilitation in lung transplant candidates: a systematic review. BMJ Open. 2017;7(2):e013445. doi:10.1136/bmjopen-2016-013445
    CrossRef - PubMed
    
18. Gloeckl R, Halle M, Kenn K. Interval versus continuous training in lung transplant candidates: a randomized trial. J Heart Lung Transplant. 2012;31(9):934-941. doi:10.1016/j.healun.2012.06.004
    CrossRef - PubMed
    
19. Jastrzebski D, Gumola A, Gawlik R, Kozielski J. Dyspnea and quality of life in patients with pulmonary fibrosis after six weeks of respiratory rehabilitation. J Physiol Pharmacol. 2006;57 Suppl 4:139-148.
    CrossRef - PubMed
    
20. Kenn K, Gloeckl R, Soennichsen A, et al. Predictors of success for pulmonary rehabilitation in patients awaiting lung transplantation. Transplantation. 2015;99(5):1072-1077. doi:10.1097/TP.0000000000000472
    CrossRef - PubMed
    
21. Li M, Mathur S, Chowdhury NA, Helm D, Singer LG. Pulmonary rehabilitation in lung transplant candidates. J Heart Lung Transplant. 2013;32(6):626-632. doi:10.1016/j.healun.2013.04.002
    CrossRef - PubMed
    
22. Manzetti JD, Hoffman LA, Sereika SM, Sciurba FC, Griffith BP. Exercise, education, and quality of life in lung transplant candidates. J Heart Lung Transplant. 1994;13(2):297-305.
    CrossRef - PubMed
23. Polastri M, Paganelli GM, Dolci G. Can lung transplant patients efficiently exercise at home? Int J Ther Rehabil. 2019;26(12):1-4. doi:10.12968/ijtr.2019.0147
    CrossRef - PubMed
    
24. Kilic L, Pehlivan E, Balci A, Bakan ND. Effect of 8-week pulmonary rehabilitation program on dyspnea and functional capacity of patients on waiting list for lung transplantation. Turk Thorac J. 2020;21(2):110-115. doi:10.5152/TurkThoracJ.2019.18202
    CrossRef - PubMed
    
25. Wickerson L, Helm D, Gottesman C, et al. Telerehabilitation for lung transplant candidates and recipients during the COVID-19 pandemic: program evaluation. JMIR Mhealth Uhealth. 2021;9(6):e28708. doi:10.2196/28708
    CrossRef - PubMed
    
26. Choi J, Hergenroeder AL, Burke L, et al. Delivering an in-home exercise program via telerehabilitation: a pilot study of Lung Transplant Go (LTGO). Int J Telerehabil. 2016;8(2):15-26. doi:10.5195/ijt.2016.6201
    CrossRef - PubMed
    
27. Polastri, M. Physiotherapy for lung transplant candidates and recipients: time frame from pre-operative to long-term care. Int J Ther Rehabil. 2019;26(2):1-6. doi:10.12968/ijtr.2019.0032
    CrossRef - PubMed
    
28. Polastri M, Dell’Amore A, Rea F. Physiotherapeutic outcomes in patients awaiting third-time lung transplantation. Int J Ther Rehabil. 28(6):1-4. doi:10.12968/ijtr.2021.0151
    CrossRef - PubMed
    
29. Egan TM, Cooper JD. Surgical aspects of single lung transplantation. Clin Chest Med. 1990;11(2):195-205. doi:10.1016/S0272-5231(21)00687-0
    CrossRef - PubMed
    
    
30. Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med. 1986;314(18):1140-1145. doi:10.1056/NEJM198605013141802
    CrossRef - PubMed
    
31. Cullum P. Lung transplantation at King’s College Hospital. Physiotherapy. 1972;58(3):100-102.
    CrossRef - PubMed
    
32. McGregor CG, Dark JH, Hilton CJ, Freeman R, Conacher ID, Corris PA. Early results of single lung transplantation in patients with end-stage pulmonary fibrosis. J Thorac Cardiovasc Surg. 1989;98(3):350-354.
    CrossRef - PubMed
    
33. Klesney-Tait J, Eberlein M, Geist L, et al. Starting a lung transplant program: a roadmap for long-term excellence. Chest. 2015;147(5):1435-1443. doi:10.1378/chest.14-2241
    CrossRef - PubMed
    
34. Nguyen AT, Brzezinski M, Chen J, Nguyen NV, Dinh LV, Kukreja J. Lung transplant programs in developing countries: challenges, solutions, and outcomes. Curr Opin Organ Transplant. 2020;25(3):299-304. doi:10.1097/MOT.0000000000000766
    CrossRef - PubMed
    
35. Gieszer B, Radeczky P, Farkas A, et al. Lung transplant patients on Kilimanjaro. Transplant Proc. 2019;51(4):1258-1262. doi:10.1016/j.transproceed.2019.04.004
    CrossRef - PubMed
    
36. Leddington Wright S, Bloxham A, Hames T, Price M. Therapeutic perceptions in management of transplant athletes at transplant games. Phys Ther Sport. 2019;39:114-119. doi:10.1016/j.ptsp.2019.07.003
    CrossRef - PubMed