This randomized controlled, single-blind clinical trial investigates whether virtual reality (VR)-assisted, video game-based exercise training, added to a conventional pulmonary physiotherapy and rehabilitation program, improves functional level, respiratory parameters, and physical fitness in pediatric patients (5-18 years) following hematopoietic stem cell transplantation (HSCT). Participants attended 24 supervised, face-to-face exercise sessions over 8 weeks (3×/week) under physiotherapist supervision. The Experimental Group received game-based exercise using the Nintendo Wii Fit U platform with the Wii Balance Board and the Breathing Labs Breathing Games software (Slovenia) in addition to the conventional program. Outcomes included the Modified Alpha-Fit Pediatric Test Battery (vertical jump, 6-minute walk test, sit-and-reach, flamingo balance), upper-extremity isometric muscle strength (handheld dynamometry) and handgrip strength (Jamar), pulmonary function tests, maximal inspiratory and expiratory mouth pressures, accessory respiratory muscle architecture by myotonometry (MyotonPro: sternocleidomastoid, upper trapezius, pectoralis major), and ultrasound assessment of pleural thickness, diaphragm thickness, and diaphragm excursion.
Design: A randomized controlled, single-blind (assessor-blinded), parallel-group trial conducted at the Cardiopulmonary Rehabilitation Unit, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istinye University. Pediatric patients who had undergone HSCT were referred from the Pediatric Bone Marrow Transplantation Unit of Medicalpark Bahçelievler Hospital, Istanbul. Eligible patients (5-18 years) who met clinical-stability criteria and had no history of orthopedic, neurological, or cardiac disease were enrolled after written parental consent and child assent. Randomization: Stratified by sex using a computer-generated 1:1:1:1 sequence to ensure homogeneous sex distribution across the two arms. Concealment was achieved through computer allocation. Participants were assigned to (1) Control Group (CG): conventional pulmonary physiotherapy and rehabilitation, or (2) Experimental Group (EG): the same conventional program PLUS supervised, virtual reality-assisted, video game-based exercise. The outcomes assessor was blinded to group allocation; participants and treating physiotherapists could not be blinded due to the nature of the intervention. Conventional pulmonary physiotherapy program (both groups): diaphragmatic breathing; thoracic expansion exercises (chest and bilateral segmental breathing); incentive spirometry (Triflo® or Voldyne®); postural drainage and percussion; cough technique training; breathing control; range-of-motion exercises. Each session lasted 25 minutes and consisted of 2 sets × 5 repetitions with 5-6 tidal-breath rest intervals to avoid respiratory-muscle fatigue. Exercise intensity was titrated using the Modified Borg Scale, targeting perceived dyspnea/fatigue between 4 and 6 (moderate intensity). VR-assisted, video game-based program (Experimental Group only): delivered concurrently with the conventional program in 24 supervised face-to-face sessions over 8 weeks (3×/week). Two platforms were used in combination. (a) Breathing Labs Breathing Games (Breathing Labs, Slovenia): five games selected per patient preference - Balloon (level 1 weeks 1-4 → level 2 weeks 5-8), Plane (6 s → 8 s), Wolf (easy → moderate), Flowers (sunflower → rose), and Pluto (easy → moderate). Patients were seated on a backless chair to prevent falls; sessions were paused if dizziness or loss of control occurred. Visual score feedback was used to reinforce engagement. (b) Nintendo Wii Fit U with the Wii Balance Board: 8 balance/mobility-targeted games, with 4 of 8 played per session for 5 minutes each. Weight-shifting games (Balance Bubble, Table Tilt, Perfect 10, Super Hula Hoop) required mediolateral and anteroposterior weight shifts on the balance board; stepping/squatting games (Obstacle Course, Advanced Obstacle Course, Ski Jump, Basic Step) required marching, squatting, leg extension, or stepping. Participants stood with or without chair-back hand support depending on tolerance. Assessments: A blinded assessor performed pre- and post-intervention testing in fixed order across separate days to prevent fatigue. The full battery comprised: sociodemographic and disease-related variables (diagnosis, transplant type, donor type, stem-cell source, time since transplant, conditioning regimen, HLA matching) extracted from the hospital electronic medical record; bioelectrical impedance analysis (Tanita) for body composition; waist and hip circumferences and waist-to-hip ratio; pulmonary function testing on a portable spirometer (Cosmed Pony FX, Italy) per ATS/ERS criteria with single-use mouthpieces and filters (FVC, FEV1, FEV1/FVC, PEF expressed in liters and as % predicted); respiratory muscle strength using a portable electronic mouth-pressure device (Micro Medical Micro RPM, Rochester, UK) recording MIP and MEP in cmH2O (best of three trials, expressed as % age- and sex-predicted); inspiratory muscle endurance with the Powerbreath Plus MR (HaB International, Southam, UK) at 60% MIP for up to 10 minutes; peripheral muscle strength using a handheld dynamometer (Lafayette Model 01165, IN, USA) for shoulder flexors/abductors and elbow flexors/extensors bilaterally; handgrip strength with a Jamar dynamometer (Nottinghamshire, UK) in seated position with elbow at 90° and wrist neutral, best of three trials, recorded in Newtons; respiratory muscle tone of sternocleidomastoid, upper trapezius, and pectoralis major using MyotonPro (Myoton AS, Tallinn, Estonia) with the device perpendicular to the marked muscle belly, recording frequency (Hz), stiffness (N/m), decrement, relaxation time (ms), and creep; diaphragm thickness measured at the 9th intercostal space (anterior axillary line) at end-expiration using B-mode 7 MHz ultrasound (Toshiba Aplio XG, Tokyo, Japan), and right-hemidiaphragm excursion during quiet breathing, deep breathing, and sniff testing using M-mode with a 3.5 MHz curved-array transducer (left hemidiaphragm not assessed due to image-quality limitations); pleural thickness assessed by the same ultrasound system. Functional fitness was assessed via the Modified Alpha-Fit Pediatric Test Battery: 6-minute walk test on a 30 m flat corridor (cardiovascular fitness); standing long jump and Jamar handgrip (musculoskeletal fitness); sit-and-reach test using a 35 × 45 × 32 cm box (flexibility); flamingo balance test on a 50 × 4 × 3 cm beam over 1 minute (balance); waist circumference and BMI (body composition; Turkish pediatric reference values per Neyzi et al., 2015). Statistical plan: Sample size was calculated a priori with G\*Power v3.1 (two-tailed, α=0.05, power=0.80, medium effect size d=0.40), targeting n=40 (20 per group). Given the achieved sample size and the resulting Type II error risk, all variables were analyzed with non-parametric tests. Within-group changes were tested with the Wilcoxon signed-rank test; between-group comparisons used the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables. Descriptive statistics are reported as mean ± standard deviation. Post-hoc power analysis using the primary outcome (vertical jump test) within the Experimental Group yielded an effect size of 0.98 with α=0.05 and power of 0.80. Of 38 enrolled, 22 were withdrawn during the intervention (3 incomplete final assessments due to clinical instability or refusal; 1 scabies; 5 cutaneous GvHD with high-dose steroid therapy; 1 respiratory-tract infection; 6 systemic infections requiring isolation; 3 new psychiatric complications with poor prognosis; 3 relocation precluding follow-up). Sixteen participants completed the trial (CG n=8; EG n=8). Funding: Health Instıtutes of Turkiye (TÜSEB), Project No 31278, Program Code 2022-ACİL-11 Group A. The investigators declared no conflicts of interest.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
38
Physiotherapist-led pulmonary rehabilitation program (24 sessions; 3×/week × 8 weeks). Components: diaphragmatic breathing, thoracic expansion exercises, incentive spirometry, postural drainage with percussion, cough techniques, breathing control, and range-of-motion exercises. Intensity titrated by Modified Borg Scale (target 4-6).
Game-based exercise sessions delivered concurrently with the conventional program. Breathing Labs games (Balloon, Plane, Wolf, Flowers, Pluto) progressed in difficulty between weeks 1-4 and 5-8. Wii Fit U weight-shifting games (Balance Bubble, Table Tilt, Perfect 10, Super Hula Hoop) and stepping/squatting games (Obstacle Course, Advanced Obstacle Course, Ski Jump, Basic Step) were played 4 per session for 5 minutes each on the Wii Balance Board, with or without chair-back support based on tolerance. Total 24 sessions over 8 weeks.
Istinye University
Istanbul, Turkey (Türkiye)
Vertical Jump Test
Component of the Modified Alpha-Fit Pediatric Test Battery. Participant first reaches the maximum standing-reach height with one arm, then jumps vertically to the maximum reachable height; the difference between the two marks is recorded in centimeters. The best of two trials is retained. Higher values indicate greater lower-extremity power. Safety Issue: No.
Time frame: Baseline to Week 8
Diaphragm Ultrasound
Right-hemidiaphragm thickness measured at end-expiration in the 9th intercostal space (anterior axillary line) using B-mode ultrasonography with a 7 MHz transducer (Toshiba Aplio XG, Tokyo, Japan). Right-hemidiaphragm excursion measured by M-mode with a 3.5 MHz curved-array transducer during quiet breathing, deep breathing, and sniff testing. Mean of three respiratory cycles reported in millimeters. Left hemidiaphragm not assessed due to image-quality limitations.
Time frame: Baseline to Week 8
Six-Minute Walk Test
Distance walked at a self-selected pace without running on a 30 m flat corridor for 6 minutes; cardiovascular fitness measure within the Modified Alpha-Fit Pediatric Test Battery. Higher values indicate better cardiovascular endurance. Safety Issue: No.
Time frame: Baseline to Week 8
Sit-and-Reach Test
Flexibility component of the Modified Alpha-Fit Pediatric Test Battery; performed on a 35 × 45 × 32 cm sit-and-reach box. Participant pushes the marker forward as far as possible with both hands; the furthest position reached is recorded in centimeters. Higher values indicate greater hamstring/lower-back flexibility. Safety Issue: No
Time frame: Baseline to Week 8
Flamingo Balance Test
Static balance component of the Modified Alpha-Fit Pediatric Test Battery; performed barefoot on a 50 × 4 × 3 cm wooden/metal beam. The participant stands single-leg with the contralateral leg flexed against the supporting knee for 1 minute; the number of imbalances is recorded. Test is terminated and scored zero if more than 15 imbalances occur within the first 30 seconds. Lower values indicate better balance. Safety Issue: No.
Time frame: Baseline to Week 8
Upper-Extremity Isometric Muscle Strength
Maximal isometric strength of shoulder flexion, shoulder abduction, shoulder adduction, elbow flexion, and elbow extension measured bilaterally with a handheld dynamometer (Lafayette Model 01165, IN, USA) in standardized positions; the best of trials recorded per side in Newtons. Higher values indicate greater muscle strength. Safety Issue: No.
Time frame: Baseline to Week 8
Handgrip Strength
Maximal handgrip force measured bilaterally with a Jamar handheld dynamometer (Nottinghamshire, UK) in seated position with the elbow flexed to 90° and wrist in neutral; the best of three trials per side recorded in Newtons. Higher values indicate greater grip strength. Safety Issue: No.
Time frame: Baseline to Week 8
Pulmonary Function Test
Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and peak expiratory flow (PEF) measured with a portable spirometer (Cosmed Pony FX, Italy) per ATS/ERS criteria, using single-use individualized mouthpieces and filters. Reported in liters and as percent of age- and sex-predicted values. Higher values indicate better pulmonary function. Safety Issue: No.
Time frame: Baseline to Week 8
Maximal Mouth Pressures
Respiratory muscle strength assessed with a portable electronic mouth-pressure device (Micro Medical Micro RPM, Rochester, UK). MIP measured during maximal inspiration against a closed valve following maximal expiration (held 1-3 s); MEP measured during maximal expiration against a closed valve following maximal inspiration. Best of three trials reported in cmH2O and as percent predicted. Higher values indicate greater respiratory muscle strength. Safety Issue: No.
Time frame: Baseline to Week 8
Accessory Respiratory Muscle Architecture
Sternocleidomastoid, upper trapezius, and pectoralis major muscle architecture parameters quantified with a MyotonPro (Myoton AS, Tallinn, Estonia) placed perpendicular to the skin-marked muscle belly: oscillation frequency (Hz; tone), dynamic stiffness (N/m), logarithmic decrement (elasticity), mechanical relaxation time (ms), and creep. Standardized resting position. Safety Issue: No.
Time frame: Baseline to Week 8
Pleural Thickness
Right-sided pleural thickness measured by ultrasonography (Toshiba Aplio XG; B-mode 7 MHz). Reported in millimeters. Safety Issue: No.
Time frame: Baseline to Week 8
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