Pulmonary rehabilitation in lung transplantation: Its effects on pulmonary function, physical fitness, and quality of life

Table 1 Pulmonary rehabilitation in lung transplantation recipients based on rehabilitation phases

Rehabilitation phase	Objective	Intervention/program
Pre-transplant (pre-LTx)	(1) Maintain or improve functional capacity and muscle strength before surgery; and (2) Reduce the risk of post-operative complications, accelerate recovery, and improve QoL	(1) Aerobic training and upper- and lower-limb strength training performed 2-3 times per week for 6-8 weeks; exercise intensity progressively increased according to individual tolerance; inspiratory breathing exercises; interval, resistance, or single-leg training modalities; (2) Initial assessment: Hemodynamic stability, oxygen requirements, bone mineral status, BMI, comorbidities, respiratory mechanics, functional capacity (6MWT, CPET), muscle strength, and QoL; and (3) Education and supportive care: Familiarization with surgical procedures; secretion management, controlled coughing techniques, incentive spirometry, wound care and pain management, and early mobilization; disease-specific education (oxygen therapy, pharmacological treatment, activities of daily living, pacing, and energy conservation); psychological support, nutritional counseling, and occupational therapy
Post-LTx hospitalization	(1) Reduce weakness associated with ICU-acquired weakness; and (2) Improve lower-extremity muscle strength, balance, and gait performance to minimize the risk of falls	(1) Initiated within 24 hours postoperatively: Early mobilization, breathing exercises, airway clearance, and postural optimization; (2) Respiratory reconditioning, evaluation of supplemental oxygen requirements, strengthening of upper-extremity and lower-extremity ROM, and management of neuropathic pain; (3) Supervised ambulation and bed-to-chair transfer training, with careful management of chest tubes and pain; (4) Gradual lower-extremity resistance training, with attention to upper-limb ROM and loading restrictions during the first approximately 6 weeks; and (5) Provision of medical and adaptive equipment at hospital discharge
Early post-LTx phase (0-12 months)	(1) Improve exercise capacity, muscle strength, QoL, participation in daily activities; and (2) Prevent complications associated with immunosuppression, diabetes, osteoporosis, and tendinopathy	(1) Early initiation of outpatient PR following hospital discharge; (2) Baseline assessment of functional capacity and muscle strength; (3) Progressive exercise training with gradual increases in intensity and duration; (4) Hygiene education to prevent infection and reduce the risk of graft rejection; (5) Interval training, warm-up, and stretching exercises to prevent tendon injury; and (6) Monitoring of comorbidities and postoperative medication adjustments
Long-term post-LTx phase (> 12 months)	(1) Maintain or further improve exercise capacity and muscle function; and (2) Address long-term effects of chronic rejection, reduce dyspnea, and enhance QoL	(1) Combined aerobic and resistance training of the upper and lower extremities, performed 3-5 times per week; (2) Gradual progression of exercise duration (30-120 minutes per week) at an intensity of 50-80% of peak work rate; (3) Remote monitoring or telehealth-based supervision; (4) Emphasis on structural muscle adaptations, including mitochondrial function, strength, type I and II muscle fiber composition, and fiber cross-sectional area; and (5) Supervised outpatient programs for patients experiencing functional decline or chronic rejection

LTx: Lung transplantation; QoL: Quality of life; ICU: Intensive care unit; BMI: Body mass index; 6MWT: Six-minute walk test; CPET: Cardiopulmonary exercise testing; ROM: Range of motion; PR: Pulmonary rehabilitation.

Table 2 Summary of studies on effects of pulmonary rehabilitation on functioning in lung transplantation recipients

No.	Ref.	Study design	Study objective	Study population	Pulmonary rehabilitation intervention	Outcomes assessed	Main results
1	Ambrosino et al[29], 1996	Prospective longitudinal	To evaluate the trajectory of exercise capacity and skeletal and respiratory muscle function after heart-lung transplantation	11 HLT patients (age 38 ± 13 years)	Maximal treadmill exercise, resistive inspiratory training, limb strength training	Pulmonary function; 6MWD; VO2 peak; MIP/MEP; lower-limb muscle strength	No significant change in pulmonary function; gradual improvements in VO2 peak, 6MWD, and muscle strength, but values remained below normal
2	Andrianopoulos et al[17], 2019	Pre-post study	To assess the short-term effects of post-LTx PR on pulmonary function, exercise capacity, and cognitive function	24 LTx recipients with COPD	Comprehensive inpatient PR for 3 weeks	DLCO; RV/TLC; 6MWD; cognitive function	DLCO increased, hyperinflation decreased, 6MWD improved significantly (+ 86 m), and cognitive function improved
3	Candemir et al[22], 2019	Pre-post study	To evaluate the effectiveness of outpatient PR after bilateral LTx	23 bilateral LTx recipients	Multidisciplinary outpatient PR for 8 weeks	Exercise capacity; muscle strength; pulmonary function; QoL; psychological status	Significant improvements in exercise capacity, muscle strength, QoL, and psychological status; static pulmonary function did not change
4	Kerti et al[21], 2021	Pre-post study	To evaluate the effectiveness of PR before and after transplantation	63 LTx candidates and 14 LTx recipients	Four-week PR: Personalized breathing and aerobic exercise	Pulmonary function; 6MWD; CWE; dyspnea; QoL	Pre-LTx PR improved CWE, CAT score, and 6MWD; post-LTx PR improved pulmonary function and quality of life
5	Munro et al[18], 2009	Prospective repeated-measures	To describe functional changes during post-LTx PR	36 LTx recipients	Outpatient PR for 12 weeks (3 times per week)	6MWD; FEV1; FVC; QoL (SF-36)	Significant improvements in pulmonary function, 6MWD, and all SF-36 domains
6	Langer et al[23], 2012	Randomized controlled trial	To evaluate the effect of early supervised exercise after LTx on functional recovery	40 LTx patients (intervention n = 21; control n = 19)	Supervised exercise for 3 months	Daily activity; physical fitness; QoL	The exercise group showed greater daily walking time, higher 6MWD, and greater muscle strength
7	Maury et al[20], 2008	Cohort study	To assess the impact of post-LTx rehabilitation on muscle function and exercise tolerance	36 LTx patients	Outpatient PR for 3 months	Quadriceps strength; 6MWD; pulmonary function	Significant improvements in 6MWD and muscle strength, but values did not reach normal levels
8	Ulvestad et al[31], 2020	Randomized controlled trial	To evaluate the effects of HIIT on fitness and muscle strength after LTx	54 LTx recipients	Supervised HIIT for 20 weeks	VO2 peak; muscle strength; QoL; pulmonary function	No significant difference in VO2 peak (ITT); improvements in muscle strength and mental components of QoL
9	Bartels et al[33], 2011	Observational study	To compare pulmonary function and exercise capacity before and after LTx	153 LTx recipients	Post-LTx PR and physical exercise	Pulmonary function; CPET	Pulmonary function improved significantly, but VO2 peak remained < 50% of predicted values
10	van Adrichem et al[34], 2015	Longitudinal cohort	To analyze changes in 6MWD and its predictors after LTx	108 LTx recipients	Recommendation for regular exercise after LTx	6MWD; pulmonary function; muscle strength	6MWD improved significantly; FEV1 and muscle strength predicted optimal functional recovery
11	Ulvestad et al[24], 2020	Cohort study	To assess respiratory fitness, physical activity, and factors contributing to exercise intolerance after LTx	54 LTx recipients	Postoperative PR up to 6 months	Cardiorespiratory fitness; physical activity	VO2 peak after BLTx remained low due to deconditioning, ventilatory limitation, and impaired gas exchange; most patients were physically inactive
12	Mei et al[25], 2024	Quasi-experimental	To evaluate the effectiveness of early comprehensive PR after LTx	LTx patients at Shanghai Pulmonary Hospital	Multidisciplinary comprehensive PR initiated 24 hours postoperatively	Pulmonary function; 6MWD; QoL; clinical outcomes	Shorter ICU LOS and better pulmonary function, 6MWD, and QoL compared with controls
13	Schneeberger et al[30], 2017	Retrospective cohort	To evaluate PR outcomes in SLTx and DLTx	722 LTx recipients	Multimodal inpatient PR (approximately 6 weeks)	6MWD; HRQoL	Significant improvements in 6MWD and HRQoL with no difference between SLTx and DLTx
14	Orens et al[36], 1995	Prospective	To evaluate exercise responses during the first year after single and double lung transplantation	14 SLTx and 11 DLTx recipients, stable ≥ 3 months post-LTx	Incremental cycle ergometer CPET every 3 months for 1 year	CPET variables; spirometry; DLCO; MVV	Lung function differed between groups, but exercise responses were similar; VO2 peak increased at 3-6 months then declined at 9-12 months
15	Dierich et al[32], 2013	Prospective observational cohort	To observe the influence of postoperative clinical course on inpatient PR success	Single, double, and combined LTx recipients (≥ 18 years)	Three-week inpatient PR: Interval training, strength training, respiratory physiotherapy, education, psychological support	PWR; VO2 peak; 6MWD; VC; FEV1; ADL; HRQoL	All physical function parameters and HRQoL improved significantly; differences observed in PWR, 6MWD, and SF-36 physical functioning
16	Byrd et al[19], 2024	Retrospective non-inferiority	To compare group-based vs individual PR	110 LTx recipients	Outpatient group-based vs individual PR	6MWD; physical function; QoL	Individual PR was non-inferior to group-based PR
17	Song et al[39], 2018	Retrospective cohort	To evaluate feasibility and outcomes of early PR initiated in the ICU after LTx	22 LTx recipients	Early ICU PR: Chest physiotherapy, limb ROM, position changes, functional progression (G1-G4)	Physical functional level	PR initiated at a median of 7.5 days post-LTx without complications; 64% achieved ambulation before discharge
18	Wu et al[35], 2022	Randomized controlled trial	To evaluate the effects of early extubation combined with physical exercise after LTx	96 LTx patients (intervention n = 48; control n = 48)	Early extubation plus early physical exercise 3-5 times per week for 4 weeks	Pulmonary function; 6MWD; MBI; LOS; satisfaction	Intervention group showed better pulmonary function, 6MWD, and MBI (P < 0.001), shorter intubation duration and LOS, and higher satisfaction
19	Fuller et al[38], 2017	Randomized controlled trial	To compare short-duration (7 weeks) vs long-duration (14 weeks) PR after LTx	66 LTx recipients	Supervised PR 3 times per week: Aerobic and resistance training	6MWD; quadriceps/hamstring strength; QoL	Both groups improved in 6MWD and muscle strength with no significant difference between program durations

LTx: Lung transplantation; PR: Pulmonary rehabilitation; HIIT: High-intensity interval training; 6MWD: Six-minute walk distance; SLTx: Single lung transplantation; DLTx: Double lung transplantation; ICU: Intensive care unit; HLT: Heterotopic liver transplantation; COPD: Chronic obstructive pulmonary disease; CPET: Cardiopulmonary exercise testing; ROM: Range of motion; VO₂ peak: Peak oxygen uptake; MIP: Maximal inspiratory pressure; MEP: Maximal expiratory pressure; ; DLCO: Diffusing capacity of the lung for carbon monoxide; MVV: Maximal voluntary ventilation; RV: Residual volume; TLC: Total lung capacity; QoL: Quality of life; CWE: Constant work-rate exercise; FEV1: Forced expiratory volume in one second; FVC: Forced vital capacity; SF-36: Short Form 36; CPET: Cardiopulmonary exercise testing; HRQoL: Health-related quality of life; PWR: Peak work rate; VC: Vital capacity; ADL: Activities of daily living; MBI: Modified Barthel Index; LOS: Length of stay; CAT: Chronic obstructive pulmonary disease assessment test; ITT: Intention-to-treat; BLTx: Bilateral lung transplantation.

Table 3 Physiological mechanism of functional improvements after pulmonary rehabilitation in lung transplantation recipients

Domain/output	Repair mechanism	Factors affecting the amount of improvement
Lung function	Progressive breathing exercises increase respiratory muscle strength and endurance, resulting in increased FEV1, FVC, faster extubation, optimal ventilation	ICU length of stay, transplant type, patient baseline condition, exercise intensity, and adherence
Cardiorespiratory fitness/exercise tolerance	Aerobic and HIIT training improves work capacity, oxygen efficiency, and participation in daily activities. It also leads to increased functional exercise tolerance	Compliance with exercise, achieved HIIT intensity, ventilatory capacity (FEV1, respiratory reserve), time to PR initiation (< 2 years post-LTx), sedentary behavior
Muscle fitness	High-intensity resistance training increases leg muscle strength, facilitating functional activity and exercise capacity. Training respiratory muscles reduces fatigue	Initial muscle weakness, duration of ICU stays, steroid/immunosuppressive use, type of exercise (resistance vs light), compliance
Activities and participation	Increased muscle strength and exercise capacity make daily activities easier to perform with relatively lower stress. Supervised exercise increases self-efficacy	Sedentary behavior, motivation level, outpatient rehabilitation support, exercise compliance
Quality of life	Increased physical capacity, participation, and social/psychological interaction during PR improves perceptions of physical and mental health	Duration and intensity of PR, duration of hospitalization, initial condition of the patient, ceiling effect on mental scores, compliance
Cardiovascular morbidity	Physical activity lowers blood pressure through acute reductions in vascular resistance and chronic adaptations of the autonomic nervous system. Exercise prevents hypertension and diabetes after LTx	Physical activity level, extreme sedentary behavior, post-transplant lifestyle

FEV1: Forced expiratory volume in one second; FVC: Forced vital capacity; HIIT: High-intensity interval training; PR: Pulmonary rehabilitation; LTx: Lung transplantation; ICU: Intensive care unit.