|Year : 2020 | Volume
| Issue : 2 | Page : 79-84
Effects of pulmonary rehabilitation on dyspnea and functional capacity on waiting list for lung transplantation: According to obstructive or restrictive pulmonary disease
Lutfiye Kilic1, Esra Pehlivan2, Arif Balcı1, Nur Dilek Bakan3
1 Department of Pulmonary Rehabilitation, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
2 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, University of Health Sciences, Istanbul, Turkey
3 Department of Chest Disease, Memorial Sisli Hospital, Istanbul, Turkey
|Date of Submission||25-Apr-2019|
|Date of Decision||26-May-2019|
|Date of Acceptance||23-Jul-2019|
|Date of Web Publication||31-Aug-2020|
Dr. Lutfiye Kilic
Department of Pulmonary Rehabilitation, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, University of Health Sciences, Fatih, Istanbul
Source of Support: None, Conflict of Interest: None
BACKGROUND: Pulmonary rehabilitation (PR) has been shown to be effective on exercise capacity and dyspnea in lung transplantation (LTx) candidates. In this study, we aimed to investigate the efficacy of PR and to compare the outcomes in LTx candidates with obstructive and restrictive lung diseases.
METHODS: Between January 2013 and May 2018, medical data of 86 patients who were on the waiting list for LTx were retrospectively analyzed. The patients were divided into two groups based on the diagnosis as obstructive patients (Group 1) and restrictive patients (Group 2). Six-minute walking test (6MWT), the Borg scale, and the modified Medical Research Council dyspnea scores were analyzed.
RESULTS: A total of 65 patients completed the 8-week PR protocol (n = 42 in Group 1 and n = 23 in Group 2). Irrespective of the initial diagnosis, there was a significant (P < 0.05) improvement in the 6MWT distance in both groups without any statistically significant difference between the groups (Group 1, 299 m [42–548] vs. 377 m [84–561], mean increase 78 m, P < 0.001; Group 2, 337 m [70–525] vs. 396 m [139–621], mean increase 59 m, P = 0.002; Δ, P = 0.476). The effect of PR on dyspnea was significantly improved in both groups, whereas there were no differences between groups.
CONCLUSION: PR has a positive effect on exercise capacity and dyspnea in patients with both obstructive and restrictive lung diseases who are on the waiting list for LTx. Our study results suggest that PR is effective in LTx candidates, irrespective of the initial diagnosis.
Keywords: Chronic obstructive pulmonary disease, exercise training, interstitial lung disease, lung transplantation, pulmonary rehabilitation
|How to cite this article:|
Kilic L, Pehlivan E, Balcı A, Bakan ND. Effects of pulmonary rehabilitation on dyspnea and functional capacity on waiting list for lung transplantation: According to obstructive or restrictive pulmonary disease. Eurasian J Pulmonol 2020;22:79-84
|How to cite this URL:|
Kilic L, Pehlivan E, Balcı A, Bakan ND. Effects of pulmonary rehabilitation on dyspnea and functional capacity on waiting list for lung transplantation: According to obstructive or restrictive pulmonary disease. Eurasian J Pulmonol [serial online] 2020 [cited 2021 Jul 25];22:79-84. Available from: https://www.eurasianjpulmonol.com/text.asp?2020/22/2/79/294026
| Introduction|| |
Lung transplantation (LTx) is the only therapeutic option for end-stage chronic lung diseases refractory to maximal medical treatment and is associated with improved quality of life (QoL) and survival. Due to the limited number of donors, LTx candidates may wait for a long period of time on the waiting list. During this time, patients' exercise capacity is gradually reduced due to dyspnea and fatigue related to the progression of disease, especially interstitial lung disease.
Exertional dyspnea and fatigue are the most common disabling symptoms which considerably impair the QoL in patients with advanced obstructive and restrictive lung diseases. In such cases, exercise tolerance decreases due to dyspnea and fatigue. The exercise capacity, which is used in predicting the success rate of LTx, is very limited in LTx candidates with end-stage lung disease.
In recent years, pulmonary rehabilitation (PR) is recommended in many transplantation centers; however, there is no established PR guideline for LTx candidates and recipients. Both LTx and PR date back to the same period in the 1960s and 1970s., In literature, the first PR program (PRP) was applied in the 1990s. With the growing number of evidences showing that PR is effective before and after surgery, PR has been mentioned in the related guidelines as a component of LTx.
Review of literature reveals a number of studies suggesting that PR can improve the dyspnea- and fatigue-induced exercise capacity in all LTx candidates with end-stage lung diseases, particularly obstructive lung disease., In addition, the physical and emotional preparation of a LTx candidate before surgery may reduce the risk for postoperative complications and improve the patient-centered outcomes.,, Such an attempt is also useful for clinicians in identifying eligible candidates and for patients in reducing physical and emotional stress. In clinical practice, PR is recommended as a part of care in this patient population.
The benefits of PR have not been exactly well documented in LTx candidates on the waiting list. To date, a few number of studies are available with heterogeneous sampling and nonstandardized protocols. In a study, Gloeckl et al. included patients with chronic obstructive pulmonary disease (COPD); Nishiyama et al. included patients with idiopathic pulmonary fibrosis (IPF); while Jastrzebski et al., Florian et al., Kenn et al., Li et al., and Manzetti et al. included different diagnoses and number of patients on the waiting list for LTx. Despite these limitations, PR has been shown to be associated with a significant improvement in functional capacity and QoL., In addition, many studies demonstrating the benefits of exercise training in patients with end-stage chronic lung diseases and COPD have been published. However, restraining patients from PR before LTx can be deemed as unethical. Therefore, it is unlikely to design a randomized controlled study of PR in LTx candidates.
Considering the physiological alterations before LTx and exercise training guidelines, an effective and safe program can be applied. In literature, there is a limited number of studies investigating the efficacy of PR according to the diagnosis (i.e., chronic obstructive lung disease and restrictive lung disease). We believe that establishing the efficacy of PR according to the diagnosis would pave the way for tailoring individual programs and for developing specific PR techniques for each patient.
In the present study, we hypothesized that the presence of end-stage lung disease-related factors would affect the PR response and that individualized programs would increase the efficacy of PR in LTx candidates. Therefore, we aimed to investigate the efficacy of PR and to compare the outcomes in LTx candidates with similar physiopathological characteristics.
| Methods|| |
Study design and study population
Between January 2013 and May 2018, medical data of 86 patients who were on the waiting list for LTx at the transplantation centers located in Istanbul province and who were referred to the PR unit of Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital were retrospectively analyzed. The patients were divided into two groups based on the diagnosis as obstructive patients (Group 1, n = 42) and restrictive patients (Group 2, n = 23). Six-minute walking test (6MWT), the Borg scale, and the modified Medical Research Council (mMRC) dyspnea scores of the patients were recorded at baseline and at the end of 8-week PRP.
Content of pulmonary rehabilitation program
The PRP involved muscle strengthening exercises, aerobic training, clinical evaluation, psychiatric evaluation, nutritional counseling, social assistance, and educational lectures. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki. Ethics committee approval was received for this study from the local Ethics Committee of the Ministry of Health, Istanbul Training and Research Hospital (approval date: 14/9/2018, document number 1415).
Clinical evaluation and exercise protocol
All patients underwent clinical evaluation by an experienced pulmonologist in the PR unit and received an education on their disease and treatment options. The patients were also given psychological support to decrease anxiety for LTx surgery. All patients received education on daily practice encouraging healthy behaviors such as regular physical activity, healthy diet, reasonable drug use, compliance to treatment, and disease self-management and psychological support including effective strategies to overcome chronic conditions. The patients who were in need of medical treatment were referred to a psychiatrist. In addition, training on the utilization of home oxygen delivery systems and inhaled drugs and strategies to overcome dyspnea and relaxation exercises were imparted.
All patients underwent exercise program twice a week under supervision for 8 weeks. In addition, they were asked to perform a home-based exercise program which was scheduled as 3 days/week and to fill out the exercise follow-up form. During the exercise program, all patients received continuous oxygen therapy in accordance with the medical prescription and were monitored with pulse oximetry. The oxygen flow rate was set to maintain an oxygen saturation of >88%.
The exercise intensity was predetermined to be 50%–70% of the maximum heart rate. The exercise intensity was gradually increased based on the severity of dyspnea perception and fatigue ratio. The aerobic exercise program consisted of treadmill walking, cycle ergometer, and arm ergometer training. Group exercises were performed in sets of 15 min each with three exercise modalities. During the exercises, oxygen saturation, heart rate, and the Borg scores were recorded.
The resistance targets were set at loads equivalent to 20%–40% of a one-repetition maximum maneuver and performed between 8 and 12 repetitions for one to two sets per session. Dumbbell and free weight bags were used in supervised exercise sessions. The training focused on exercise for biceps, triceps, quadriceps, hamstring, and hip muscles.
Home-based exercise program
In addition to the supervised exercise program which was administered for 2 days at the hospital, the patients were asked to perform a home-based exercise program for 3 days a week. The program included breathing exercises (local expansion exercises, diaphragmatic breathing, and pursed lip breathing), free walking, and upper- and lower-extremity strengthening exercises with TheraBand ®. To ensure that the home-based exercise program was performed, a patient home-based exercise follow-up chart was given to each patient and chart follow-ups on a weekly basis were carried out by the physiotherapist.
- 6MWT – The test was conducted in a 30-m corridor according to the American Thoracic Society (ATS) guidelines. Before and after the test, oxygen saturation, heart rate, Borg rating, and walking distance were recorded 
- mMRC-Dyspnea Scale – Perceived dyspnea during the activities of daily living was evaluated using the mMRC scale.
Statistical analysis was performed using the SPSS version 15 statistical software (SPSS Inc., Chicago, IL, USA). Descriptive data were expressed in mean and standard deviation, median (minimum–maximum), number (n), and frequency (%). The Shapiro–Wilk test was used to test the normality of the distribution of all variables. The Wilcoxon signed-rank test was used to compare the pre- and post-exercise results of the groups, whereas the Mann–Whitney U-test was used for group-wise comparisons. The Chi-square test was used to analyze categorical variables. P < 0.05 was considered statistically significant.
| Results|| |
Of all the patients, 65 completed (n = 42 in Group 1 and n = 23 in Group 2) the 8-week PR protocol. Twenty-one (24.4%) patients were unable to complete the program for several reasons. Of the completers, 55% and 87% were male and 64.6% and 35.4% were female in Group 1 and Group 2, respectively. The mean age was 37.59 years in Group 1 and 41.21 years in Group 2, indicating no significant difference. The study's flowchart is depicted in [Figure 1]. The number of male patients (P = 0.009) and the mean body mass index (P = 0.014) were statistically significantly higher in Group 2 than Group 1. However, the mean pulmonary artery systolic pressure was higher in Group 1 (41.28 mmHg) than Group 2, although not statistically significant.
|Figure 1: Study's flowchart. COPD: Chronic obstructive lung disease, IPF: Idiopathic pulmonary fibrosis, PLCH: Pulmonary Langerhans cell histiocytosis|
Click here to view
The most common diagnoses in Group 1 included bronchiectasis in 25 patients (59.5%, P < 0.001), COPD in 13 patients (31%), and cystic fibrosis in four patients (9.5%). The most common diagnoses in Group 2 included IPF in ten patients (39.1%), silicosis in nine patients (39.1%), sarcoidosis in three patients (13.1%), and histiocytosis in one patient (4.3%). [Table 1] summarizes the demographic and clinical characteristics of both patient groups.
Pulmonary rehabilitation program effects
Functional exercise capacity
The distance from the 6MWT was compared with that of the reference values. No statistically significant differences were found in the increased 6MWT distance values (Δ, P = 0.476) between Group 1 (77.41 m, P < 0.001) and Group 2 (59.34 m, P = 0.002) [Table 2]. Irrespective of the initial diagnosis, there was a significant (P < 0.05) improvement in the 6MWT distance in both groups without any statistically significant difference between the groups (Group 1, 299 m [42–548] vs. 377 m [84–561], mean increase 78 m, P < 0.001; Group 2, 337 m [70–525] vs. 396 m [139–621], mean increase 59 m, P = 0.002). Despite the low mean 6MWT distance at baseline, the mean increase in the distance after PRP was significant in Group 1.
|Table 2: Dyspnea, fatigue, and exercise capacities before and after pulmonary rehabilitation|
Click here to view
Although a statistically significant decrease was achieved in the mMRC dyspnea score of both groups (Group 1, P < 0.001; Group 2, P = 0.046), there was no statistically significant difference between the groups (P = 0.447) [Table 2]. The effect of PRP on dyspnea was statistically significantly improved in Group 1 (Borg, resting: P = 0.005, postexercise: P = 0.003, and mMRC: P < 0.001) and Group 2 (Borg, resting: P = 0.036, postexercise: P = 0.011, and mMRC: P < 0.001). The dyspnea scores and exercise capacities of both groups before and after PRP are shown in [Table 2].
| Discussion|| |
In the present study, we evaluated the effect of an 8-week PRP on dyspnea and exercise capacity in LTx candidates with end-stage obstructive or restrictive lung diseases. We found that PRP yielded a clinical improvement in these patients, irrespective of the initial diagnosis. More interestingly, although the mean baseline 6MWT distance was worse in the obstructive patients (299 m) than the restrictive patients (337 m), a higher increase was found after PRP in the obstructive patients (77.4 m vs. 59.3 m). This situation may be due to a ceiling effect of the 6MWT due to the physical limitation of the possible extent of fast walking. Although the median increase in neither group was statistically significant (P = 0.476), the increase in the 6MWT distance was higher than the minimal clinically important difference (25–33 m) as recommended by the ATS/European Respiratory Society. In the entire study population, the median increase in the 6MWT distance after exercise was statistically significant (68.37 m) (P < 0.05). In a study, Florian et al. reported a 72-m increase in the 6MWT distance in patients undergoing 32-session PRP (P = 0.001). In the aforementioned study, patients with interstitial lung disease were also included, as in our study; however, the underlying diseases were not considered in the final analysis. In another study, Kaymaz et al. applied an 8-week PRP to patients with interstitial lung disease (n = 10) and found a 60-m increase in the median 6MWT distance, which is consistent with our findings related to the patients with interstitial lung disease, despite a higher number of sample size in our study (n = 42). Similarly, Holland et al. reported a 57-m increase with an 8-week PRP and Nishiyama et al. reported a 46.3-m increase with a 10-week PRP.
In our study, we also observed a statistically significant (P < 0.05) clinical improvement in the perceived dyspnea scores in both groups (Group 1, Borg, resting: P = 0.005, postexercise: P = 0.003, and mMRC: P < 0.001 vs. Group 2, Borg, resting: P = 0.036, postexercise: P = 0.011, and mMRC: P < 0.001). On the other hand, some authors have advocated that 8-week PRP twice a week under supervision is not effective. However, the British Thoracic Society recommends a 6-week exercise program twice a week under supervision. In our study, the distance in 6MWT increased after PRP and less fatigue at the end of the test in both groups.
Because restrictive lung disease is associated with rapid desaturation during exercise, a lower intensity and long-term exercise program appears to be more effective in this patient population. However, it should be kept in mind that such group of diseases may rapidly progress. Unfortunately, there is no randomized study available on the content and optimal duration of the program in LTx candidates; therefore, we use empirical data based on our clinical observations. According to previous study findings, we consider that a longer duration for PRP is needed to optimize the exercise capacity of patients with restrictive lung disease than those with obstructive lung disease. Although several lung volume-lowering techniques have been developed to maintain the exercise capacity and QoL in COPD patients who have been waiting for LTx for a long period of time, there is no option, but the early referral to PRP for patients with restrictive lung disease. Current evidences have not recommended an optimal duration of PRP for patients with restrictive lung disease; however, early referral seems to be associated with favorable results.
The majority of the referral patients to the LTx centers are COPD patients. Interestingly, 75% of our patients were diagnosed other than COPD (i.e., bronchiectasis in 44% and silicosis in 30%). This can be attributed to the fact that younger patients with a higher life expectancy following transplantation were mostly selected for LTx previously. However, the lack of expected increase in the survival over time indicates that more efforts should be paid to refer COPD patients to the transplantation centers and that pulmonologists in Turkey, particularly working in regional hospitals, have limited knowledge and familiarity on transplantation or may overlook this issue.
In literature, a few number of studies are available on LTx candidates investigating the efficacy of PRP with heterogeneous sampling and small sample sizes. In our study, we classified the patients into groups according to their physiopathological characteristics and attempted to contribute to the existing data from a different perspective. Nonetheless, small sample size and patient classification according to the underlying physiopathological mechanism alone can be deemed as the main limitations of this study. In addition, we were only able to evaluate the first 8-week outcomes of PRP in which the sample size was the highest. Finally, we were unable to evaluate emotional aspects and health-related QoL in our study.
| Conclusion|| |
Irrespective of the initial diagnosis, PR had a positive effect on exercise capacity and dyspnea in patients with both obstructive and restrictive lung diseases who were on the waiting list for LTx. We believe that the present study is important in that it provides PRP responses of patients with similar physiopathological characteristics, which would pave way for tailoring individual programs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Florian J, Rubin A, Mattiello R, Fontoura FF, Camargo Jde J, Teixeira PJ, et al.
Impact of pulmonary rehabilitation on quality of life and functional capacity in patients on waiting lists for lung transplantation. J Bras Pneumol 2013;39:349-56.
Smith CM. Patient selection, evaluation, and preoperative management for lung transplant candidates. Clin Chest Med 1997;18:183-97.
Bolton CE, Bevan-Smith EF, Blakey JD, Crowe P, Elkin SL, Garrod R, et al.
British thoracic society guideline on pulmonary rehabilitation in adults. Thorax 2013;68 Suppl 2:ii1-30.
Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al.
Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 2017;195:557-82.
Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al.
An official American thoracic society/European respiratory society statement: Key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188:e13-64.
Trojetto T, Elliott RJ, Rashid S, Wong S, Dlugosz K, Helm D, et al.
Availability, characteristics, and barriers of rehabilitation programs in organ transplant populations across Canada. Clin Transplant 2011;25:E571-8.
Benfield JR, Wain JC. The history of lung transplantation. Chest Surg Clin N
Am 2000;10:189-99, xi.
Casaburi R. A brief history of pulmonary rehabilitation. Respir Care 2008;53:1185-9.
Dear C, Grossman R, Maurer J. Preoperative evaluation of patients awaiting lung transplant. Chest 1988;94: 30S.
Gloeckl R, Halle M, Kenn K. Interval versus continuous training in lung transplant candidates: A randomized trial. J Heart Lung Transplant 2012;31:934-41.
Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery CF, Mahler DA, et al.
Pulmonary rehabilitation: Joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest 2007;131:4S-42S.
Jastrzebski D, Ochman M, Ziora D, Labus L, Kowalski K, Wyrwol J, et al.
Pulmonary rehabilitation in patients referred for lung transplantation. Adv Exp Med Biol 2013;755:19-25.
Palmer SM, Tapson VF. Pulmonary rehabilitation in the surgical patient. Lung transplantation and lung volume reduction surgery. Respir Care Clin N
Nishiyama O, Kondoh Y, Kimura T, Kato K, Kataoka K, Ogawa T, et al.
Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis. Respirology 2008;13:394-9.
Kenn K, Gloeckl R, Soennichsen A, Sczepanski B, Winterkamp S, Boensch M, et al.
Predictors of success for pulmonary rehabilitation in patients awaiting lung transplantation. Transplantation 2015;99:1072-7.
Li M, Mathur S, Chowdhury NA, Helm D, Singer LG. Pulmonary rehabilitation in lung transplant candidates. J Heart Lung Transplant 2013;32:626-32.
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;13:297-305.
Holland AE, Wadell K, Spruit MA. How to adapt the pulmonary rehabilitation programme to patients with chronic respiratory disease other than COPD. Eur Respir Rev 2013;22:577-86.
Schneeberger T, Gloeckl R, Welte T, Kenn K. Pulmonary rehabilitation outcomes after single or double lung transplantation in patients with chronic obstructive pulmonary disease or interstitial lung disease. Respiration 2017;94:178-85.
Pepin V, Brodeur J, Lacasse Y, Milot J, Leblanc P, Whittom F, et al.
Six-minute walking versus shuttle walking: Responsiveness to bronchodilation in chronic obstructive pulmonary disease. Thora×2007;62:291-8.
Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al.
An official European respiratory society/American thoracic society technical standard: Field walking tests in chronic respiratory disease. Eur Respir J 2014;44:1428-46.
Kaymaz D, Ergün P, Candemir I, Utku E, Demir N, Şengül F, et al.
Pulmonary rehabilitation in interstitial lung diseases. Tuberk Toraks 2013;61:295-302.
Holland AE, Hill CJ, Glaspole I, Goh N, McDonald CF. Predictors of benefit following pulmonary rehabilitation for interstitial lung disease. Respir Med 2012;106:429-35.
Ringbaek TJ, Broendum E, Hemmingsen L, Lybeck K, Nielsen D, Andersen C, et al.
Rehabilitation of patients with chronic obstructive pulmonary disease. Exercise twice a week is not sufficient! Respir Med 2000;94:150-4.
British Thoracic Society Standards of Care Subcommittee on Pulmonary Rehabilitation. Pulmonary rehabilitation. Thorax 2001;56:827-34.
Dowman L, McDonald CF, Hill C, Lee A, Barker K, Boote C, et al.
The benefits of exercise training in interstitial lung disease: Protocol for a multicentre randomised controlled trial. BMC Pulm Med 2013;13:8.
Salhi B, Troosters T, Behaegel M, Joos G, Derom E. Effects of pulmonary rehabilitation in patients with restrictive lung diseases. Chest 2010;137:273-9.
Büyükkale S, Bakan NK, Isgörücü Ö, Çitak N, Cenger D, Demir A, et al
. Late-breaking abstract:First 24 lung transplantations: Single center results from Turkey. Eur Respir J 2014; 44 Suppl 58:2450.
Dabak G, Dalar L, Taşçı E, Clark S. Lung transplantation in Turkey: Lessons from surgeons and pulmonologists. Turk J Med Sci 2016;46:1434-42.
[Table 1], [Table 2]