A Protocol for Multidisciplinary Rehabilitation Combined with Enzyme Replacement Therapy for Ventilator Weaning in Late-Onset Pompe Disease

Podsumowanie

This protocol describes a multidisciplinary rehabilitation approach integrated with enzyme replacement therapy to support ventilator weaning in a patient with late-onset Pompe disease through structured respiratory training, physical rehabilitation, nutritional management, psychological support, and standardized extubation assessment.

Streszczenie

Late-onset Pompe disease (LOPD) is a rare autosomal recessive lysosomal storage disorder caused by acid alpha-glucosidase deficiency, resulting in progressive skeletal and respiratory muscle weakness that may lead to chronic respiratory insufficiency and prolonged dependence on mechanical ventilation. Although enzyme replacement therapy (ERT) can slow disease progression, successful ventilator weaning often requires coordinated multidisciplinary management. This protocol describes a reproducible rehabilitation approach integrated with ERT to support ventilator weaning and extubation in patients with LOPD. The method combines pharmacological treatment with structured respiratory rehabilitation, physical training, nutritional management, psychological support, and traditional Chinese medicine–based interventions, including auricular acupuncture and seated Tai Chi. The protocol also incorporates standardized assessment procedures, individualized treatment planning, ventilator weaning strategies, and objective criteria for evaluating extubation readiness. Emphasis is placed on collaboration among physicians, rehabilitation therapists, nurses, nutritionists, and psychologists to address the complex needs of patients with neuromuscular respiratory impairment. The approach is illustrated through its application in an adult patient with LOPD who required prolonged mechanical ventilation. This protocol provides a practical framework that may be adapted across clinical settings to support respiratory recovery, rehabilitation participation, and ventilator weaning in patients with LOPD and related neuromuscular disorders.

Wprowadzenie

Pompe disease is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the acid alpha-glucosidase (GAA) gene. The resulting deficiency of lysosomal GAA impairs glycogen degradation and leads to progressive glycogen accumulation, particularly in skeletal, cardiac, and respiratory muscles. The reported frequency of Pompe disease varies among populations and according to the methods used for case identification. In a nationwide Belgian cohort, the prevalence of late-onset Pompe disease (LOPD) was estimated at 3.9 cases per million individuals¹.

Pompe disease is generally classified into infantile-OPD (IOPD) and LOPD according to the age at clinical presentation, cardiac involvement, residual enzyme activity, and rate of disease progression. IOPD commonly presents during the first year of life with generalized hypotonia, profound muscle weakness, feeding difficulty, respiratory distress, and hypertrophic cardiomyopathy. In contrast, LOPD may become clinically apparent during childhood, adolescence, or adulthood and is more commonly characterized by progressive axial and proximal limb-girdle weakness and respiratory insufficiency, with severe cardiomyopathy occurring less frequently². Without timely diagnosis and treatment, rapidly progressive cardiac and respiratory involvement in IOPD may lead to early cardiopulmonary failure, whereas LOPD generally follows a more variable and gradually progressive course³.

Although the two phenotypes differ in their age at onset and predominant organ involvement, both may affect multiple physiological and functional domains. Patients may require coordinated surveillance and treatment involving neuromuscular function, respiratory status, cardiac involvement, swallowing, nutrition, mobility, psychological well-being, and caregiver support. LOPD should therefore not be regarded exclusively as a limb-girdle myopathy, because clinically relevant involvement of respiratory, bulbar, vascular, gastrointestinal, and other systems has increasingly been recognized⁴.

Respiratory impairment may appear early in LOPD and can develop independently of, or become disproportionately severe relative to, limb weakness. Weakness of the diaphragm and accessory respiratory muscles reduces inspiratory capacity and may produce a marked decrease in vital capacity when the patient moves from an upright to a supine position. Respiratory dysfunction may also involve expiratory and abdominal muscles, thereby reducing cough effectiveness and the ability to clear airway secretions⁵. Progressive respiratory muscle weakness can subsequently lead to sleep-disordered breathing, nocturnal hypoventilation, daytime hypercapnia, recurrent respiratory infection, atelectasis, and chronic ventilatory failure⁶.

As respiratory function deteriorates, some patients require nocturnal or intermittent non-invasive ventilation. Continuous ventilatory assistance may later become necessary, particularly when respiratory muscle reserve declines or an acute infection, secretion retention, aspiration, or another physiological stressor precipitates acute-on-chronic respiratory failure. Invasive mechanical ventilation may be required when non-invasive support fails, airway protection is inadequate, or the secretion burden cannot be managed safely. Liberation from invasive ventilation is particularly difficult when inspiratory muscle weakness, ineffective cough, retained secretions, physical deconditioning, anxiety, and poor tolerance of spontaneous breathing occur simultaneously.

Enzyme replacement therapy (ERT) with recombinant human GAA is an established disease-specific treatment for Pompe disease. In a randomized controlled trial involving patients with LOPD, alglucosidase alfa was associated with improvement in walking capacity and stabilization of forced vital capacity during an 18-month treatment period⁷. Nevertheless, treatment responses vary, and ERT may not fully reverse advanced respiratory muscle damage, prolonged immobility, ineffective airway clearance, or the functional consequences of critical illness. Pharmacological treatment therefore needs to be combined with respiratory and rehabilitative management when a patient has developed substantial ventilatory impairment.

Existing respiratory-care guidelines for neuromuscular disease recommend serial evaluation of respiratory function, individualized non-invasive or invasive ventilatory support, assessment of cough effectiveness, assisted airway-clearance techniques, and coordinated planning for transitions between ventilatory modalities⁸. These principles are applicable to patients with LOPD and provide the clinical foundation for ventilator-weaning decisions. Readiness for extubation should therefore not be determined by a single respiratory index. Respiratory mechanics, gas exchange, secretion burden, cough effectiveness, bulbar function, mental status, hemodynamic stability, spontaneous-breathing tolerance, and the availability of post-extubation non-invasive support should be considered together.

Physical rehabilitation may complement respiratory management by reducing secondary deconditioning and preserving mobility, postural control, transfer capacity, and participation in daily activities. A 12-week program combining aerobic, resistance, and core-stability exercises was feasible and beneficial in ambulatory adults with Pompe disease receiving ERT⁹. However, findings obtained from clinically stable ambulatory patients cannot be transferred directly to individuals receiving prolonged invasive mechanical ventilation. In ventilated patients, rehabilitation intensity must be adjusted according to hemodynamic stability, ventilatory support, oxygenation, perceived exertion, muscle fatigue, and recovery after each session.

Nutritional management is also relevant because reduced mobility, muscle loss, swallowing impairment, insufficient protein intake, and altered energy expenditure may influence functional recovery. Nutritional assessment should therefore accompany exercise and respiratory rehabilitation, with energy and protein provision individualized according to body composition, swallowing safety, clinical stress, and rehabilitation demands¹⁰. In addition, anxiety, fear of breathlessness, and distress during spontaneous-breathing trials may reduce treatment participation and should be assessed as part of multidisciplinary care.

Despite growing recognition of rehabilitation in LOPD, the available literature provides limited operational detail on how ERT, invasive ventilator weaning, airway-clearance procedures, physical training, nutritional care, and psychological support should be coordinated within a single clinical pathway¹¹. The present article addresses this practical gap by describing a structured multidisciplinary rehabilitation protocol as it was implemented in one adult patient with confirmed LOPD who required prolonged invasive mechanical ventilation after respiratory deterioration and an unsuccessful initial weaning attempt.

The protocol combined continued ERT with respiratory rehabilitation, airway-clearance procedures, progressive physical training, nutritional management, psychological support, repeated assessment of spontaneous-breathing tolerance, and selected traditional Chinese medicine-based interventions, including auricular acupuncture and seated Tai Chi. The traditional Chinese medicine-based components were used as adjunctive measures within this individualized rehabilitation program. They were not intended to replace ERT, invasive or non-invasive ventilatory support, airway management, or established neuromuscular respiratory care.

This article does not propose a universally applicable treatment guideline or suggest that every component should be used in all patients with Pompe disease. Rather, it provides a reproducible account of the clinical sequence, monitoring procedures, progression criteria, safety thresholds, and multidisciplinary responsibilities used in this representative case. The core elements may be adapted for other patients with Pompe disease or related neuromuscular disorders who require prolonged mechanical ventilation. Any adaptation should be guided by disease severity, respiratory mechanics, bulbar function, secretion burden, comorbidities, treatment tolerance, patient preferences, and locally available clinical expertise.

To demonstrate implementation of the protocol, the following representative case describes an adult patient with confirmed LOPD who required prolonged invasive mechanical ventilation after respiratory deterioration and an unsuccessful initial weaning attempt. A 21-year-old Han Chinese male university student was admitted because of severe pneumonia, respiratory failure, and difficulty with ventilator liberation. Diagnostic evaluation confirmed LOPD through markedly reduced peripheral leukocyte GAA activity, pathogenic GAA variants, and skeletal muscle biopsy findings compatible with glycogen storage disease type II. The patient presented with respiratory-muscle weakness, ineffective cough, secretion retention, severe malnutrition, and failed ventilator weaning despite prior medical management, providing the clinical basis for implementation of the multidisciplinary rehabilitation protocol combined with ERT.

Protokół

Conduct all procedures involving the patient in accordance with the Declaration of Helsinki and the requirements of the Institutional Research Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. ZSLL-ZN-2024-039-01). This protocol was developed from and implemented in the representative adult patient with confirmed LOPD described above. Obtain written informed consent from the patient or the patient’s legally authorized representative for treatment, study-related data collection, and publication of de-identified clinical information before protocol implementation.

1. Patient Preparation and Initial Assessment

1. Review eligibility and source records.
   1. Confirm that the patient has LOPD, requires invasive or recently invasive ventilatory support, is medically stable enough to participate in staged rehabilitation, and has provided informed consent through the patient or legally authorized representative.
   2. Review the clinical history for neuromuscular weakness, respiratory-muscle involvement, ineffective cough, secretion retention, previous ventilatory support, previous ERT, and the acute event associated with the current respiratory deterioration.
   3. Verify that diagnostic and treatment records contain consistent patient and specimen identifiers.
2. Confirm the biochemical, genetic, and pathological diagnosis.
   1. Confirm the diagnosis using GAA enzyme testing, GAA molecular analysis, and muscle histopathology when available, in accordance with established diagnostic recommendations and variant-classification frameworks for Pompe disease and genetic testing^12,13,14,15 (see Supplementary File 1).
3. Obtain the baseline clinical assessment.
   1. Perform the baseline assessment within 24 h after cardiorespiratory stabilization and before the first structured rehabilitation session.
   2. Position the patient with the head of the bed elevated by 30°–45° and allow at least 10 min of rest before measurement. Record ventilator settings, vital signs, oxygenation, consciousness level, secretion burden, suction frequency, and end-tidal carbon dioxide when available.
   3. Obtain an arterial blood gas sample and record pH, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, bicarbonate, base excess, and lactate.
   4. Assess muscle strength using the Medical Research Council scale and assess cough effectiveness, swallowing ability, aspiration risk, and airway-protection ability.
4. Assess psychological and functional status.
   1. Record the Richmond Agitation-Sedation Scale score and administer the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 when the patient can communicate reliably.
   2. Record functional status using the Barthel Index, Medical Research Council sum score, sitting tolerance, transfer ability, standing tolerance, and walking status.
5. Determine the mode of ventilatory support.
   1. Use non-invasive ventilation when the patient is conscious, cooperative, hemodynamically stable, able to protect the airway, and able to manage secretions.
   2. Proceed to orotracheal intubation when respiratory failure progresses despite optimized non-invasive ventilation or when airway protection, gas exchange, or secretion management becomes inadequate.
   3. Consider tracheostomy when prolonged invasive ventilation is anticipated, repeated extubation attempts fail, airway protection remains inadequate, or secretions remain unmanageable despite optimized airway clearance.
6. Establish the multidisciplinary treatment plan.
   1. Convene the multidisciplinary team (MDT) within 24 h after protocol initiation. Define treatment objectives, intervention frequency, responsible team members, progression criteria, and safety thresholds.
   2. Conduct a daily multidisciplinary review of respiratory status, ventilator support, rehabilitation progress, nutritional status, and psychological tolerance.
7. Confirm eligibility for active rehabilitation and spontaneous breathing assessment.
   1. Proceed with active rehabilitation when LOPD is confirmed, ventilatory support is required, medical stability permits participation, and informed consent has been obtained.
   2. Before spontaneous breathing assessment, confirm hemodynamic stability, adequate oxygenation, manageable secretions, and an appropriate level of consciousness.
8. Measure baseline respiratory mechanics.
   1. Measure maximal inspiratory pressure or negative inspiratory force, maximal expiratory pressure when feasible, and peak cough flow using calibrated equipment. Obtain at least three technically acceptable measurements and record the best value.
   2. Calculate the rapid shallow breathing index as respiratory rate divided by tidal volume in liters and interpret the result together with respiratory mechanics, gas exchange, secretion burden, and spontaneous-breathing tolerance.
9. Perform scheduled and unscheduled monitoring.
   1. Record vital signs, ventilator parameters, sedation level, symptom scores, secretion characteristics, and interventions at standardized monitoring intervals.
   2. Repeat assessments immediately when clinically significant deterioration or respiratory distress occurs.
      NOTE: Detailed source-record review, diagnostic methods, molecular testing procedures, sequencing quality-control criteria, histopathology methods, ventilatory-support documentation, tracheostomy criteria, respiratory-mechanics calibration procedures, and monitoring documentation requirements are provided in Supplementary File 1. References supporting the diagnostic framework and variant-classification procedures are cited in the main protocol text^12,13,14,15.

2. Administration of ERT

1. Calculate and verify the alglucosidase alfa dose.
   1. Measure actual body weight within 24 h before each infusion using a calibrated standing, chair, or bed scale according to mobility status.
   2. Calculate alglucosidase alfa at 20 mg/kg every 2 weeks using actual body weight. Use ideal or adjusted body weight only when substantial fluid overload makes actual body weight unsuitable and the alternative calculation is approved by the metabolic-disease specialist.
   3. Require two licensed clinicians to independently verify patient identity, body weight, calculated dose, number of 50 mg vials, lot numbers, expiration dates, dilution volume, and infusion-pump settings.
2. Reconstitute, dilute, and administer alglucosidase alfa.
   1. Reconstitute each 50 mg vial with 10.3 mL of sterile water for injection. Confirm a final reconstituted concentration of 5 mg/mL and inspect the solution before dilution.
   2. Dilute the calculated dose in 0.9% sodium chloride injection to 0.5–4 mg/mL.
   3. Use a dedicated infusion pump, low-protein-binding tubing, and an in-line low-protein-binding 0.2 µm filter. Do not administer another medication through the same line.
   4. Begin infusion at 1 mg/kg/h. If no infusion-associated reaction occurs, increase every 30 min to 3 mg/kg/h, 5 mg/kg/h, and a maximum of 7 mg/kg/h.
   5. Follow the current prescribing information for alglucosidase alfa during dose calculation, reconstitution, dilution, filtration, storage, and administration¹⁶.
3. Monitor the patient during infusion.
   1. Position the patient in a monitored bed or reclining chair with immediate access to oxygen, suction, and airway equipment. Use continuous electrocardiography and pulse oximetry during infusion.
   2. Record heart rate, respiratory rate, blood pressure, mean arterial pressure, oxygen saturation, temperature, consciousness level, ventilator settings, and end-tidal carbon dioxide when available before infusion and throughout monitoring.
   3. Assess for flushing, pruritus, rash, urticaria, facial or oral swelling, throat tightness, wheezing, stridor, chest discomfort, nausea, headache, chills, fever, dyspnea, and anxiety.
   4. Record vital signs and symptoms every 15 min during the first 30 min, immediately before each rate increase, and every 30 min thereafter. Increase monitoring frequency when symptoms or clinically important physiological changes occur.
   5. Stop rate escalation when clinical instability occurs. Reduce the infusion to the previously tolerated rate or temporarily stop it, assess airway, breathing, and circulation, notify the physician, and document the event and response.
4. Prepare for and manage infusion-associated reactions.
   1. Keep emergency medications, oxygen, suction, airway equipment, defibrillator, and emergency cart immediately accessible during each infusion. Stop the infusion immediately and activate the institutional emergency response when anaphylaxis or severe respiratory deterioration is suspected.
   2. Apply established anaphylaxis diagnostic criteria and first-line epinephrine treatment recommendations¹⁷. Continue, postpone, reduce, or discontinue ERT according to infusion tolerance, clinical stability, and metabolic-disease specialist review.
   3. Apply risk-based premedication and post-infusion observation for patients with previous infusion reactions or other high-risk features.
   4. Grade and report infusion-associated adverse events according to institutional pharmacovigilance requirements.
      NOTE: Resume rehabilitation only after the patient has returned to the pre-infusion cardiorespiratory baseline and has no unresolved infusion-associated symptoms. Detailed procedures for dose verification, infusion preparation, monitoring thresholds, emergency management, premedication, adverse-event grading, and pharmacovigilance documentation are provided in Supplementary File 2. References supporting alglucosidase alfa administration and anaphylaxis management are cited in the main protocol text^16,17.

3. Physical Rehabilitation

1. Determine readiness and rehabilitation level.
   1. Conduct rehabilitation under a licensed physiotherapist trained in neuromuscular rehabilitation, mechanical ventilation, cardiopulmonary monitoring, airway-emergency recognition, and safe patient handling.
   2. Perform physiotherapy for approximately 30 min per session, 5 days per week. Divide the session into shorter blocks when continuous activity is not tolerated.
   3. Assign the initial rehabilitation level according to functional capacity. Use Level 1 for positioning and in-bed activity, Level 2 for bed mobility and supported sitting, Level 3 for sitting balance and low-load resistance exercise, and Level 4 for sit-to-stand practice, standing balance, stepping, and assisted walking.
   4. Advance by one level after two consecutive sessions are completed without a stop criterion and after cardiovascular, respiratory, neurological, and musculoskeletal safety screening¹⁸.
2. Perform mobility and strengthening exercises.
   1. Perform postural transitions from supine to head elevation, sitting, and standing as tolerated.
   2. Begin strengthening with 3–5 min of active-assisted range-of-motion exercise.
   3. Train upper-limb, lower-limb, and core muscle groups using gravity-reduced movement, elastic bands, cuff weights, hand weights, body weight, or therapist-applied resistance according to muscle strength and ventilatory tolerance.
   4. Select an initial resistance that allows 10–12 repetitions with correct technique and a Borg Category-Ratio 10 score no higher than 4.
   5. Perform one set for muscles graded 2–3 on the Medical Research Council scale and two sets for muscles graded at least 4. Progress to a maximum of three sets after two tolerated sessions.
   6. Do not train to muscular failure or use heavy eccentric loading. Use published Pompe disease exercise evidence as the basis for low-to-moderate resistance training while reducing the dose for a mechanically ventilated patient¹⁹.
3. Progress exercise intensity and apply stop criteria.
   1. Assess exercise tolerance using heart rate, blood pressure, oxygen saturation, respiratory rate, Borg exertion and dyspnea scores, movement quality, and recovery time.
   2. Increase resistance by approximately 5%, and by no more than 10% at one time, after two consecutive tolerated sessions.
   3. Reduce workload by 20%–30% when excessive fatigue, dyspnea, delayed recovery, oxygen desaturation, or compensatory movement occurs.
   4. Provide a planned 2–5 min rest interval after approximately every 10 min of activity and whenever Borg score reaches 5 or physiological tolerance deteriorates.
   5. Suspend or terminate rehabilitation when major physiological instability, oxygen desaturation, clinically significant arrhythmia, severe dyspnea, marked anxiety, or failure to recover occurs.
4. Reassess functional progress weekly.
   1. Reassess the Medical Research Council sum score, Intensive Care Unit Mobility Scale, sitting duration, transfer assistance, standing duration, and walking distance every 7 days.
   2. Use the Intensive Care Unit Mobility Scale to record the highest mobility level achieved²⁰.
   3. Perform the 30-s chair-stand test when the patient can stand from a stable chair without physical lifting assistance²¹.
   4. Progress rehabilitation when at least two functional indicators improve without a safety violation.
      NOTE: Pause rehabilitation when mean arterial pressure falls below 65 mmHg, temperature exceeds 38.5°C, a clinically significant arrhythmia develops, oxygen saturation remains below 92% for at least 1 min, end-tidal carbon dioxide increases by more than 10 mmHg with intolerance, or anxiety prevents safe participation. Resume rehabilitation only after correction of the precipitating condition and confirmation of cardiorespiratory stability. Detailed rehabilitation levels, transfer support procedures, orthostatic-intolerance criteria, exercise sequences, progression rules, termination definitions, and weekly reassessment procedures are provided in Supplementary File 3. References supporting rehabilitation safety screening, Pompe disease exercise prescription, mobility scoring, and chair-stand testing are cited in the main protocol text^18,19,20,21.

4. Respiratory Rehabilitation

1. Review and adjust ventilatory support.
   1. Review ventilator settings, respiratory mechanics, gas exchange, secretion burden, respiratory pattern, and work of breathing at least once daily and after any clinically important change.
   2. Record ventilator mode, oxygen concentration, positive end-expiratory pressure or expiratory positive airway pressure, pressure support or inspiratory pressure, respiratory rate, tidal volume, minute ventilation, peak airway pressure, trigger sensitivity, and alarm limits.
   3. Increase ventilatory support when respiratory rate exceeds 30 breaths/min with distress, tidal volume decreases, carbon dioxide rises with acidemia, accessory-muscle use or paradoxical breathing develops, or the patient cannot sustain the current support level.
   4. Reduce pressure support by 1–2 cmH₂O only when respiratory rate, oxygenation, pH, tidal volume, comfort, and consciousness remain stable.
2. Perform airway-clearance and respiratory-muscle training.
   1. Maintain oxygen saturation at 92%–96% in patients without chronic hypercapnia and 88%–92% in documented chronic carbon dioxide retainers.
   2. Perform active cycle of breathing techniques two to three times daily using breathing control, thoracic expansion, huffing, and directed cough as needed²².
   3. Perform diaphragmatic breathing in a semi-recumbent or seated position.
   4. Perform inspiratory muscle training using a pressure-threshold device or validated ventilator-based function. Set the initial load at 30% of the most recent maximal inspiratory pressure or negative inspiratory force, perform three sets of 6–10 resisted breaths two to three times daily, and do not exceed 40% of maximal inspiratory pressure during the initial phase²³.
   5. Reduce inspiratory-muscle training resistance when fewer than six breaths can be completed, accessory-muscle use increases, or Borg dyspnea reaches at least 5.
3. Conduct the spontaneous breathing trial.
   1. Confirm readiness by verifying improvement of the acute cause of respiratory deterioration, hemodynamic stability, oxygen saturation of at least 92% with fraction of inspired oxygen no greater than 0.40 and positive end-expiratory pressure no greater than 8 cmH₂O, manageable secretions, appropriate consciousness, and absence of major metabolic instability.
   2. Conduct the spontaneous breathing trial (SBT) using either a T-piece or low-level pressure support because current guidance does not require a single SBT method or mandatory rapid shallow breathing index calculation before starting the trial²⁴.
   3. Begin pressure-support trials at 5 cmH₂O with positive end-expiratory pressure no greater than 5 cmH₂O and increase pressure support to no more than 8 cmH₂O only when immediate excessive work of breathing occurs.
   4. Conduct the first trial for 30 min. Extend to 60 min after previous failure or uncertain tolerance and to a maximum of 120 min when prolonged observation is required.
   5. Continuously monitor respiratory rate, oxygen saturation, heart rate, electrocardiographic rhythm, respiratory pattern, mental status, dyspnea, and secretion burden during the trial.
   6. Terminate the trial when sustained tachypnea, oxygen desaturation, severe distress, hemodynamic instability, clinically significant arrhythmia, worsening consciousness, or inability to clear secretions occurs.
   7. Return the patient to pretrial support, correct reversible causes, and repeat the trial approximately 24 h later when stability is restored.
4. Assess respiratory mechanics and cough effectiveness.
   1. Calculate the rapid shallow breathing index at approximately 30 min by dividing respiratory rate by tidal volume in liters. Use the result as supportive information only and do not use it as the sole extubation criterion.
   2. Measure negative inspiratory force through the endotracheal tube using the ventilator function or a calibrated pressure manometer. Treat −20 cmH₂O or more negative as minimum supportive evidence and −30 cmH₂O or more negative as a preferred, but not mandatory, target.
   3. Measure peak cough flow using a calibrated flow-measurement device. Treat unassisted peak cough flow below 270 L/min as an indication to plan cough assistance and below 160 L/min as evidence of severely ineffective cough²⁵.
   4. Provide breath stacking, lung-volume recruitment, manually assisted cough, or mechanical insufflation-exsufflation when cough effectiveness remains inadequate. Individualize mechanical insufflation-exsufflation pressures rather than applying one fixed setting to every patient²⁶.
5. Confirm extubation-related respiratory readiness.
   1. Recommend extubation only when the SBT is tolerated, gas exchange and hemodynamics are acceptable, airway protection is adequate, mental status is appropriate, cough is effective, and secretions are manageable.
   2. Perform cuff-leak assessment only when the patient otherwise meets extubation criteria and has increased risk of post-extubation stridor. Do not use a failed cuff-leak test as the sole reason for indefinite delay; when the patient is otherwise ready, administer physician-prescribed systemic corticosteroid for at least 4 h before extubation²⁷.
   3. Confirm arterial oxygen tension of at least 60 mmHg on fraction of inspired oxygen no greater than 0.40, pH of at least 7.32, and arterial carbon dioxide increase no greater than 10 mmHg from baseline when arterial blood gas testing is clinically indicated.
   4. Record the trial method, duration, settings, oxygen level, respiratory-mechanics findings, gas-exchange results, secretion burden, cough assessment, failure criteria, corrective actions, and final extubation decision.
      NOTE: After a failed spontaneous breathing trial, return the patient to comfortable non-fatiguing support. Repeat the trial after reversible causes have been corrected and hemodynamics, oxygenation, mental status, and secretion control are stable. Detailed ventilator-adjustment procedures, oxygen titration rationale, active-cycle technique details, equipment maintenance, spontaneous-breathing-trial monitoring definitions, failure thresholds, reversible-cause correction, cough-assistance settings, cuff-leak calculation, and gas-exchange documentation procedures are provided in Supplementary File 4. References supporting airway-clearance techniques, inspiratory muscle training, spontaneous breathing trials, cough-flow thresholds, mechanical insufflation-exsufflation, and cuff-leak management are cited in the main protocol text^{22,23,24,25,26,27}.

5. Nutritional and Psychological Support

1. Determine nutritional targets.
   1. Complete the initial nutritional assessment within 24 h after protocol initiation.
   2. Prescribe 25 kcal/kg/day during the early low-activity or medically unstable phase and increase toward 30 kcal/kg/day when cardiorespiratory status is stable and rehabilitation intensity increases. Use indirect calorimetry when available.
   3. Use actual body weight when body mass index is below 30 kg/m² and adjusted body weight when body mass index is at least 30 kg/m².
   4. Prescribe protein at 1.2 g/kg/day during the initial low-activity phase and increase progressively to 1.3–1.5 g/kg/day during active resistance, mobility, and respiratory-muscle training when renal and metabolic tolerance is adequate. Prefer measured energy expenditure when available and increase protein progressively during acute critical illness²⁸.
2. Provide fluid, fiber, and enteral nutrition.
   1. Begin with a total fluid target of 25–30 mL/kg/day and adjust according to fluid balance, renal function, cardiac status, respiratory status, and secretion characteristics.
   2. Provide 20–25 g of fiber daily when gastrointestinal function is intact and suspend fiber when gastrointestinal contraindications or severe feeding intolerance occurs.
   3. Use continuous pump feeding when the patient is mechanically ventilated or has high aspiration risk. Maintain head-of-bed elevation at 30°–45° during feeding.
   4. Confirm initial feeding-tube position radiographically before first use and verify tube position before subsequent use according to institutional procedures. Use a standardized enteral-feeding process to reduce preventable feeding errors²⁹.
3. Reassess nutrition and monitor complications.
   1. Reassess body weight, cumulative energy and protein delivery, metabolic status, renal function, hepatic function, inflammatory status, and complete blood count every 7 days.
   2. Assess refeeding-syndrome risk before initiating or substantially increasing nutrition. In high-risk patients, begin at 10–20 kcal/kg during the first 24 h, administer thiamine 100 mg before initiating nutrition, and monitor electrolytes closely³⁰.
   3. Record feeding tolerance, aspiration signs, gastrointestinal symptoms, stool frequency, stool consistency, and actual feeding delivery each day.
   4. Manage bowel function using the Bristol Stool Form Scale, targeting one comfortable bowel movement every 1–2 days with Bristol type 3–4 stool³¹.
4. Provide psychological support and relaxation training.
   1. Provide individual bedside counseling twice weekly for 20–30 min by a licensed psychologist, psychiatrist, or mental-health professional trained in medically complex or critical-care patients.
   2. Review anxiety related to breathlessness, ventilator weaning, sleep disruption, coping resources, communication difficulty, treatment expectations, and family support.
   3. Repeat the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 every 7 days and after clinically important psychological change.
   4. Increase counseling to three to five brief sessions per week when either Generalized Anxiety Disorder-7 or Patient Health Questionnaire-9 score is at least 10, and request psychiatric consultation when either score is at least 15, symptoms substantially interfere with participation, or an immediate safety concern is identified^32,33.
   5. Perform paced breathing for 15–20 min when anxiety is associated with tachypnea, breath-holding, or spontaneous-breathing trials. Use guided imagery for 10–15 min when respiratory pacing is stable but persistent worry, sleep difficulty, or anticipatory anxiety remains.
      NOTE: Detailed nutritional calculations, enteral-feeding procedures, refeeding-syndrome monitoring, bowel-management procedures, psychological escalation criteria, and relaxation-training documentation are provided in Supplementary File 5. References supporting nutrition support, enteral-feeding safety, refeeding-syndrome classification, stool assessment, anxiety screening, and depression screening are cited in the main protocol text^{28,29,30,31,32,33}.

6. Integration of Traditional Chinese Medicine Interventions

1. Prepare for auricular acupuncture.
   1. Perform auricular acupuncture once daily for 20 min using single-use sterile needles administered by a licensed traditional Chinese medicine physician or acupuncturist trained in auricular acupuncture, infection prevention, and emergency response.
   2. Position the patient semi-recumbent at 30°–45° or seated with head and neck support. Inspect the auricle and do not perform needling when local infection, severe skin disease, active bleeding, or other contraindications are present.
   3. Locate Shenmen (TF4), Heart (CO15), and Sympathetic (AH6a) according to the Chinese national standard GB/T 13734—2008³⁴.
   4. Insert needles superficially into the selected auricular points, retain for 20 min, monitor patient tolerance throughout treatment, and remove needles with confirmation of hemostasis after treatment completion.
2. Conduct seated Tai Chi.
   1. Perform seated Tai Chi under supervision of a licensed physiotherapist or traditional Chinese medicine rehabilitation therapist trained in Tai Chi, cardiopulmonary monitoring, and basic life support.
   2. Use a simplified Yang-style seated program consisting of opening and closing, cloud hands, wave hands like clouds, parting the wild horse’s mane, brush knee and push, and closing movements.
   3. Begin with a warm-up period, perform movements at a slow continuous pace coordinated with relaxed breathing, avoid breath-holding and painful movements, and conclude with relaxation breathing exercises.
   4. Perform one session daily during the initial phase and increase to two sessions daily only when oxygen saturation remains at least 92%, heart-rate increase remains below 20 beats/min, respiratory rate remains 8–20 breaths/min, Borg exertion and dyspnea scores remain no higher than 3, and recovery occurs within 5 min.
   5. Use Tai Chi only as an adjunctive low-intensity mind–body exercise and not as a replacement for conventional respiratory or physical rehabilitation. Tai Chi has been studied as an adjunct or alternative form of pulmonary rehabilitation in chronic respiratory disease³⁵.
3. Monitor safety and treatment tolerance.
   1. Record heart rate, respiratory rate, oxygen saturation, Borg Category-Ratio 10 exertion and dyspnea scores, and pain score before, during, and after Tai Chi sessions.
   2. Reduce exercise intensity or provide additional rest when symptoms, physiological intolerance, excessive exertion, dyspnea, or pain develop.
   3. Stop Tai Chi when oxygen saturation falls below 92% or decreases by at least 3 percentage points from baseline, or when dizziness, chest discomfort, marked dyspnea, arrhythmia, loss of postural control, or distress develops.
   4. Monitor auricular acupuncture for local or systemic adverse events and monitor Tai Chi for exercise-related adverse events. Grade and document all traditional Chinese medicine-related adverse events and review them during MDT meetings before resuming treatment.
      NOTE: Detailed auricular-acupuncture procedures, needling techniques, contraindication thresholds, Tai Chi progression criteria, intensity-adjustment algorithms, adverse-event grading, and documentation requirements are provided in Supplementary File 6.

7. Extubation and Weaning Process

1. Confirm extubation readiness.
   1. Confirm readiness using integrated assessment of spontaneous-breathing-trial tolerance, respiratory strength, cough effectiveness, secretion burden, airway protection, mental status, gas exchange, and hemodynamic stability.
   2. Use maximal inspiratory pressure or negative inspiratory force, peak cough flow, respiratory pattern, and spontaneous-breathing tolerance rather than respiratory-muscle Medical Research Council grading.
   3. Confirm successful completion of a SBT lasting 30–120 min without predefined failure criteria.
   4. Complete the standardized extubation-readiness checklist before tube removal.
2. Perform extubation.
   1. Confirm immediate availability of trained personnel, suction equipment, oxygen-delivery devices, non-invasive ventilation equipment, cough-assistance devices, emergency airway equipment, and reintubation medications.
   2. Position the patient with 45°–60° head elevation, suction oral and endotracheal secretions, remove the endotracheal tube according to institutional practice, and immediately apply the planned post-extubation respiratory support.
   3. Assess airway patency, cough effectiveness, secretion clearance, respiratory pattern, oxygenation, and mental status immediately after extubation.
3. Select post-extubation respiratory support.
   1. Use conventional oxygen therapy in clinically stable low-risk patients.
   2. Apply prophylactic non-invasive ventilation immediately or within 1 h after extubation in high-risk patients ventilated for more than 24 h, consistent with ATS/CHEST guidance³⁶.
   3. Use high-flow nasal oxygen when non-invasive ventilation is not immediately required or during breaks from non-invasive ventilation.
   4. Reassess respiratory status regularly and reduce support progressively when respiratory stability is maintained.
4. Identify and manage post-extubation respiratory distress.
   1. Recognize post-extubation respiratory distress by worsening oxygenation, increasing respiratory effort, secretion retention, impaired airway protection, deteriorating consciousness, or escalating oxygen or ventilatory requirements.
   2. Intensify airway-clearance measures and non-invasive support when deterioration is potentially reversible and airway protection remains adequate.
   3. Do not delay reintubation when respiratory arrest, refractory hypoxemia, worsening acidemia, inability to protect the airway, uncontrolled secretions, severe upper-airway obstruction, hemodynamic instability, or deteriorating consciousness occurs.
5. Manage extubation failure and respiratory retraining.
   1. Define extubation failure as reintubation within 72 h after planned extubation.
   2. Identify the principal cause of failure and initiate targeted correction.
   3. When respiratory-muscle weakness contributes to failure, implement respiratory retraining with inspiratory-muscle training, diaphragmatic breathing, airway-clearance therapy, assisted cough, graded mobilization, nutritional optimization, and reduction of unnecessary sedation.
   4. Use mechanical insufflation–exsufflation when cough effectiveness remains inadequate or peak cough flow remains severely reduced, in accordance with established neuromuscular-airway-clearance recommendations³⁷.
   5. Reassess respiratory mechanics, cough effectiveness, secretion burden, gas exchange, airway protection, and spontaneous-breathing tolerance before another extubation attempt.
      NOTE: Detailed extubation-readiness thresholds, secretion-management criteria, post-extubation support settings, monitoring schedules, extubation-failure classification, respiratory-retraining procedures, independent breathing practice, mechanical insufflation–exsufflation parameters, and documentation requirements are provided in Supplementary File 7. References supporting post-extubation non-invasive ventilation and cough-assistance strategies are retained in the main protocol text^36,37.

8. Post-extubation Monitoring and Follow-up

1. Continue post-extubation rehabilitation and monitoring.
   1. Continue breathing control, thoracic expansion, active cycle of breathing, assisted cough, inspiratory-muscle training, physical rehabilitation, and nutritional support after extubation.
   2. Perform airway-clearance interventions at least three times daily and additionally when secretion retention, ineffective cough, desaturation, or abnormal breath sounds develop.
   3. Monitor respiratory status, hemodynamics, oxygenation, mental status, cough effectiveness, secretion burden, airway findings, oxygen therapy, and ventilatory-support requirements during the first 72 h after extubation.
   4. Increase monitoring frequency and escalate airway-clearance interventions or medical review when respiratory, cardiovascular, neurological, or airway instability develops.
2. Conduct follow-up and home rehabilitation.
   1. Perform weekly follow-up assessments for 4 weeks after extubation using in-person or remote evaluation as appropriate. Assess respiratory endurance, maximal inspiratory pressure, peak cough flow, Medical Research Council sum score, mobility status, functional recovery, and psychological status.
   2. Prescribe home breathing exercises, inspiratory-muscle training, airway-clearance exercises, and mobility activities. Instruct the patient to stop exercise and seek clinical review for worsening respiratory symptoms, oxygen saturation below 92%, fever, chest pain, confusion, hemoptysis, or inability to clear secretions.
3. Define and document outcomes.
   1. Define primary treatment success as liberation from invasive mechanical ventilation within 30 days of protocol initiation without reintubation during the first 72 h after final extubation.
   2. Define improvement in limb strength as an increase of at least 3 points in the Medical Research Council sum score.
   3. Define improvement in cough function as an increase in peak cough flow of at least 10% from baseline or movement across a clinically relevant cough-assistance threshold.
   4. Define psychological improvement as a reduction of at least 5 points in the Generalized Anxiety Disorder-7 score or movement to a lower severity category.
   5. Record ventilator-free status, reintubation, tracheostomy, non-invasive ventilatory support, oxygen requirement, respiratory complications, functional status, nutritional status, adverse events, readmission, and patient-reported outcomes.
4. Review deviations and archive records.
   1. Review safety events, outcomes, missed interventions, modified interventions, and protocol deviations during multidisciplinary review. Store source documents and study records in secure institutional systems and maintain de-identification of research datasets.
   2. Retain inpatient and outpatient medical records in accordance with Chinese medical-record regulations³⁸. Retain study-specific research records according to institutional, ethical, and regulatory requirements.
   3. Maintain electronic audit trails and modification histories in accordance with Chinese electronic medical-record requirements³⁹.
      NOTE: Detailed post-extubation monitoring schedules, instability criteria, airway-clearance procedures, home-program prescriptions, adherence calculations, outcome-reporting procedures, protocol-deviation documentation requirements, and record-archiving specifications are provided in Supplementary File 8. References supporting medical-record retention and electronic-record requirements are retained in the main protocol text^38,39.

Wyniki

Reprezentatywny kliniczny profil wyjściowy

Przed przeniesieniem pacjent rozwinął w domu niemożność wykrztuszania wydzieliny z dróg oddechowych, po czym nastąpiło zatrzymanie krążenia i oddechu. Został on reanimowany w lokalnym szpitalu i przekazany na oddział chirurgicznej intensywnej terapii o wyższym stopniu referencyjności. Przed przyjęciem na oddział rehabilitacyjny otrzymał alglucosidase alfa, piperacylinę sodową i sulbaktam sodowy, enoksaparinę sodową, terapię supresji kwasu żołądkowego, leczenie wykrztuśne oraz przerywane odsysanie treści za pomocą bronchoskopu. Zalecono tracheostomię ze względu na przewidywaną długotrwałą wentylację inwazyjną, jednak rodzina odmówiła wykonania tego zabiegu.

W momencie przyjęcia na oddział rehabilitacyjny pacjent pozostawał z intubacją ustną, z rurką endotrachealną utrwaloną na głębokości 27 cm od siekaczy. Stosowano inwazyjną wentylację w trybie przerywanej obowiązkowej wentylacji synchronizowanej ciśnieniowo, przy FiO₂ wynoszącej 50%, ciśnieniu inspiracyjnym 12 cmH₂O oraz wsparciu ciśnieniowym 12 cmH₂O. Parametry życiowe wynosiły: temperatura 36,7°C; tętno 125 uderzeń/min; częstość oddechów 25 oddechów/min; ciśnienie tętnicze 119/71 mmHg; a saturacja tlenem 98% przy wsparciu wentylacyjnym. Pacjent był przytomny, lecz w stanie znacznego wyniszczenia. Szmery oddechowe były osłabione obustronnie, stwierdzono obecność wilgotnych rzężeń, siła kaszlu była słaba, a plwocina biała i ropna.

Manualne badanie siły mięśni wykazało wyraźne osłabienie proksymalne. Obustronna siła mięśni proksymalnych kończyn górnych była w stopniu 1, siła mięśni dystalnych kończyn górnych w stopniu 4, obustronna siła mięśni proksymalnych kończyn dolnych w stopniu 1, a siła mięśni dystalnych kończyn dolnych w stopniu 3. Formalna ocena głosu i połykania była ograniczona ze względu na intubację orotrakchealną. Ciężka dysfunkcja opuszkowa nie została odnotowana jako główna przyczyna intubacji w dostępnej dokumentacji przekazania pacjenta.

Badania laboratoryjne przy przyjęciu wykazały liczbę leukocytów wynoszącą 13,8 × 10⁹/L, odsetek neutrofili 88,6%, hemoglobinę 108 g/L, białko C-reaktywne 96,4 mg/L, prokalcytoninę 0,62 ng/mL, albuminy surowicy 28,4 g/L, aktywnośćy aminotransferazy alaninowej 86 U/L, aminotransferazy asparaginianowej 74 U/L, bilirubinę całkowitą 22,6 µmol/L, kinazę kreatynową 614 U/L, potas 3,7 mmol/L oraz fosforany 0,82 mmol/L. Początkowe wartości gazometrii krwi tętniczej przed intubacją były niedostępne, ponieważ przed przekazaniem pacjenta przeprowadzono reanimację i intubację przezrotniczą. Pierwsza dostępna gazometria krwi tętniczej po przekazaniu, uzyskana podczas wentylacji inwazyjnej przy FiO₂ 0,50, wykazała pH 7,36, PaO₂ 92 mmHg, PaCO₂ 48 mmHg, HCO₃− 27,1 mmol/L, nadmiar zasad 1,4 mmol/L oraz mleczany 1,5 mmol/L.

Tomografia komputerowa klatki piersiowej wykazała obustronne zapalenie płuc, ogniskową konsolidację i niedodmę w dolnym płacie lewym oraz czopy śluzowe w tchawicy, lewym oskrzelu głównym i oskrzelu dolnego płata lewego. Bronchoskopia potwierdziła obecność obfitej, białej wydzieliny ropnej w lewym drzewie oskrzelowym.

Ramy wdrażania i monitorowania protokołu

Wielodyscyplinarny protokół rehabilitacyjny wdrożono po ustabilizowaniu reprezentatywnego pacjenta podłączonego do inwazyjnej wentylacji mechanicznej oraz po potwierdzeniu LOPD na podstawie historii klinicznej, obniżonej aktywności GAA, patomorfologii mięśni oraz testów molekularnych GAA. Protokół obejmował kontynuację ERT, rehabilitację oddechową, wsparcie w oczyszczaniu dróg oddechowych, progresywną rehabilitację fizyczną, dietoterapię, wsparcie psychologiczne oraz pomocnicze interwencje oparte na tradycyjnej medycynie chińskiej. Cały schemat postępowania, obejmujący ocenę pacjenta, podawanie ERT, rehabilitację oddechową i fizyczną, ponowną ocenę SBT, podejmowanie decyzji o ekstubacji oraz opiekę poekstubacyjną, przedstawiono na Rysunku 1.

Rycina 1. Schemat interdyscyplinarnego protokołu rehabilitacji połączonego z terapią enzymatyczną w celu odstawienia od respiratora w późnej postaci choroby Pompego. Schemat przedstawia sekwencję obejmującą potwierdzenie diagnostyczne, ocenę wyjściową, kontynuację terapii enzymatycznej, rehabilitację oddechową i udrażnianie dróg oddechowych, progresywną rehabilitację fizyczną, wsparcie żywieniowe i psychologiczne, pomocnicze interwencje z zakresu tradycyjnej medycyny chińskiej, ponowną ocenę próby samodzielnego oddychania, ocenę gotowości do ekstubacji, planowaną ekstubację, monitorowanie po ekstubacji oraz 4-tygodniową obserwację. Skróty: ABG, gazometria krwi tętniczej; ERT, terapia enzymatyczna; GAA, alfa-glukozydaza kwasowa; GAD-7, kwestionariusz GAD-7 (Generalized Anxiety Disorder-7); MRC, Medical Research Council; NIF, maksymalny ujemny ciśnienie wdechowe; NIV, wentylacja nieinwazyjna; PCF, szczytowy przepływ kaszlu; PHQ-9, kwestionariusz PHQ-9 (Patient Health Questionnaire-9); RSBI, wskaźnik szybkiego, płytkiego oddychania; SBT, próba samodzielnego oddychania; TCM, tradycyjna medycyna chińska. Kliknij tutaj, aby wyświetlić powiększoną wersję tej ryciny.

W ciągu 3-miesięcznego okresu interwencji monitorowano seryjne wyniki oddechowe, funkcjonalne, żywieniowe, psychologiczne oraz w zakresie bezpieczeństwa. Główny przebieg kliniczny i reprezentatywne punkty końcowe monitorowania podsumowano w Tabeli 1.

Miesiąc ERTa	FiO2 (%)	Ciśnienie inspiracyjne lub poziom wsparcia ciśnieniowego (cmH2O)2O)	Kluczowy etap odstawiania od respiratora			RSBI (częstość oddechów na minutę·min-1·L-1)	NIF (cmH2O)2O)	PCF (l/min)	Wyniki gazometrycznego badania krwi tętniczej			skala MRC	wynik w skali BBS	wynik w skali GAD-7	wynik w skali PHQ-9	Wyniki analizy wartości odżywczych i bezpieczeństwa
1	50	12	Podjęto próbę SBT na prośbę rodziny; ekstubacja nie powiodła się; pacjent został ponownie zaintubowany			NR	NR	NR	Gazometria krwi tętniczej przed intubacją niedostępna ze względu na przeprowadzenie resuscytacji w trybie pilnym oraz intubację przezrotoową przed transportem			32	0	1	2	Podaż energii na poziomie 68% i podaż białka na poziomie 65% wartości docelowych; albuminy wyjściowe 28,4 g/L; brak ciężkich reakcji związanych z wlewem ERT
1.5	33	7	Przerwa od wentylacji inwazyjnej przez 2 h podczas treningu mięśni oddechowych			NR	NR	NR	NR			34	5	0	1	Żywienie enteralne tolerowane bez aspiracji ani ciężkiej nietolerancji żywienia
2	30	7	Przerwa od wentylacji inwazyjnej przez 8 h podczas treningu mięśni oddechowych			NR	NR	NR	NR			37	8	0	0	Podaż energii i białka została zwiększona w kierunku wyznaczonych celów
2.5	30	6	Przerwa od wentylacji inwazyjnej przez 10 h podczas treningu mięśni oddechowych			NR	NR	NR	NR			39	17	0	3	Nie odnotowano upadków związanych z rehabilitacją, klinicznie istotnych arytmii, krwawień lub zakażeń związanych z akupunkturą ani urazów związanych z Tai Chi
3	29	Ponieważ nie dostarczono tekstu źródłowego do przetłumaczenia, proszę o przesłanie materiałów, które mają zostać przełożone na język polski.b	Próba oddychania samodzielnego (SBT) zakończona pomyślnie; ekstubacja przebiegła pomyślnie; osiągnięto odłączenie od inwazyjnej wentylacji mechanicznej			86	−28	178	pH 7,39, PaO22 84 mmHg, PaCO22 45 mmHg, HCO3-3- 26,8 mmol/l, mleczan 1,2 mmol/l (FiO2 ≤0.40)			40	21	0	0	Dostarczenie energii na poziomie 91% i białka na poziomie 93% założonych celów; albuminy 32,1 g/L; brak reintubacji w ciągu 72 h

Tabela 1: Zmiany w wsparciu wentylacyjnym, funkcji oddechowej, efektach rehabilitacji, stanie odżywienia i bezpieczeństwie podczas enzymatycznej terapii zastępczej i rehabilitacji wielodyscyplinarnej.Tabela podsumowuje podłużne zmiany w zapotrzebowaniu na wsparcie wentylacyjne, wynikach prób samodzielnego oddychania (SBT), mechanice oddychania, skuteczności kaszlu, wynikach gazometrii krwi tętniczej, sile mięśniowej, równowadze, stanie psychologicznym, podaży żywieniowej oraz wynikach bezpieczeństwa związanych z protokołem podczas enzymatycznej terapii zastępczej (ERT) i rehabilitacji wielodyscyplinarnej. Przedstawiono kluczowe etapy odstawiania respiratora prowadzące do udanej ekstubacji, uniezależnienia od inwazyjnej wentylacji mechanicznej oraz braku reintubacji w ciągu 72 h. Skala równowagi Berga (BBS) obejmuje zakres od 0 do 56, gdzie wyższe wyniki wskazują na lepszą równowagę. Skróty: ABG, gazometria krwi tętniczej; BBS, Skala równowagi Berga; ERT, enzymatyczna terapia zastępcza; FiO₂, frakcja tlenu w mieszaninie wdechowej; GAD-7, kwestionariusz uogólnionego lęku GAD-7; HCO₃⁻, wodorowęglany; MRC, sumaryczna skala Medical Research Council; N/A, nie dotyczy; NIF, maksymalny ujemny ciśnienie wdechowe; NR, nie zapisano; PaCO₂, ciśnienie parcjalne dwutlenku węgla w krwi tętniczej; PaO₂, ciśnienie parcjalne tlenu w krwi tętniczej; PCF, szczytowy przepływ kaszlu; PHQ-9, kwestionariusz zdrowia pacjenta PHQ-9; RSBI, wskaźnik szybkiego płytkiego oddechu; SBT, próba samodzielnego oddychania. ^aMiesiąc ERT podano w przyrostach 0,5 miesiąca. ^bCiśnienie wdechowe lub poziom wsparcia ciśnieniowego przestało być stosowane po udanej ekstubacji i uniezależnieniu od inwazyjnej wentylacji mechanicznej.

Wymagania dotyczące wsparcia wentylacyjnego i tolerancja oddychania spontanicznego

W ciągu pierwszego miesiąca ERT i rehabilitacji wielodyscyplinarnej, na prośbę rodziny podjęto próbę przeprowadzenia SBT, która zakończyła się niepowodzeniem z powodu zmęczenia mięśni oddechowych i retencji wydzieliny, co wymagało ponownej intubacji.

Zapotrzebowanie na wsparcie wentylacyjne stopniowo malało w okresie interwencji. FiO₂ spadło z 50% w 1. miesiącu do 33% w 1,5. miesiącu, 30% w 2. i 2,5. miesiącu oraz 29% w 3. miesiącu. Poziom ciśnienia wdechowego/wsparcia ciśnieniowego spadł z 12 cmH₂O w 1. miesiącu do 7 cmH₂O w 1,5. i 2. miesiącu, a następnie do 6 cmH₂O w 2,5. miesiącu. Do 1,5. miesiąca pacjent tolerował 2 h przerwy od inwazyjnego wsparcia wentylacyjnego podczas treningu mięśni oddechowych. Tolerancja ta wzrosła do 8 h w 2. miesiącu i do 10 h w 2,5. miesiącu. W 3. miesiącu pacjent przeszedł pomyślnie SBT, poddano go udanej ekstubacji i zaprzestano stosowania inwazyjnego wsparcia wentylacyjnego.

Podczas ostatniego udanego SBT wskaźnik szybkiego płytkiego oddechu wynosił 86 breaths·min⁻¹·L⁻¹, ujemne ciśnienie wdechowe wynosiło −28 cmH₂O, a szczytowy przepływ kaszlu wynosił 178 L/min. Wartości gazometryczne krwi tętniczej uzyskane podczas SBT przy FiO₂ ≤ 0.40 wykazały pH 7.39, PaO₂ 84 mmHg, PaCO₂ 45 mmHg, HCO₃⁻ 26.8 mmol/L oraz poziom mleczanów 1.2 mmol/L. Wyniki te były zgodne z zdefiniowaną w protokole gotowości do ekstubacji.

Funkcje motoryczne, równowaga i wyniki psychologiczne

Obiektywna regeneracja ruchowa następowała równolegle z poprawą tolerancji oddechowej. Wynik siły mięśniowej według skali Medical Research Council wzrósł z 32 w 1. miesiącu do 34 w 1,5 miesiącu, 37 w 2. miesiącu, 39 w 2,5 miesiącu i 40 w 3. miesiącu.

Zdolność do utrzymania równowagi również uległa poprawie w okresie interwencji. Wynik w skali równowagi Berga wzrósł z 0 w 1. miesiącu do 5 w 1,5. miesiącu, 8 w 2. miesiącu, 17 w 2,5. miesiącu i 21 w 3. miesiącu.

Wyniki psychologiczne pozostały ogólnie niskie i uległy poprawie do końca okresu obserwacji. Wynik w skali Generalized Anxiety Disorder-7 spadł z 1 w 1. miesiącu do 0 od 1,5 miesiąca wzwyż. Wynik w kwestionariuszu Patient Health Questionnaire-9 wynosił 2 w 1. miesiącu, 1 w 1,5 miesiącu, 0 w 2. miesiącu, 3 w 2,5 miesiącu i 0 w 3. miesiącu.

Wsparcie żywieniowe i bezpieczeństwo protokołu

Żywienie dojelitowe było tolerowane przez cały okres interwencji bez podejrzenia aspiracji, ciężkiej nietolerancji żywienia, krwawień z przewodu pokarmowego ani przerw wymagających zaprzestania wsparcia żywieniowego. Dobowa podaż energii wzrosła z około 68% zaplanowanego celu w 1. miesiącu do 91% w 3. miesiącu, a dobowa podaż białka wzrosła z około 65% do 93% zaplanowanego celu w tym samym okresie. Poziom albuminy w surowicy wzrósł z 28,4 g/L przy pomiarze wyjściowym do 32,1 g/L w 3. miesiącu.

W ciągu 3-miesięcznego okresu protokołu nie odnotowano żadnych ciężkich reakcji związanych z infuzją, wstrząsu anafilaktycznego, upadków związanych z rehabilitacją, klinicznie istotnych arytmii, krwawień lub infekcji związanych z nakłuciami, urazów związanych z praktyką Tai Chi ani poważnych zdarzeń niepożądanych związanych z protokołem. Żadna infuzja ERT nie została trwale przerwana z powodu reakcji związanej z infuzją.

Wynik ekstubacji i stabilność po ekstubacji

W 3. miesiącu, po kontynuacji zintegrowanej terapii ERT oraz wielodyscyplinarnej rehabilitacji, pacjent przeszedł pomyślnie próbę odłączenia od respiratora (SBT) i został pomyślnie ekstubowany po spełnieniu kryteriów gotowości do ekstubacji zdefiniowanych w protokole.

Wstępne wartości gazometrii krwi tętniczej sprzed intubacji były niedostępne, ponieważ przed przekazaniem pacjenta na oddział rehabilitacyjny przeprowadzono reanimację nagłą oraz intubację przezrotoową. Pierwszy dostępny wynik gazometrii krwi tętniczej po przekazaniu wykazał pH 7.36, PaO₂ 92 mmHg przy wsparciu wentylacyjnym, PaCO₂ 48 mmHg, HCO₃⁻ 27.1 mmol/L oraz mleczany 1.5 mmol/L.

W ciągu 2 h po ekstubacji u pacjenta wystąpiła przejściowa tachypnoe oraz niepokój. Objawy te ustąpiły po zastosowaniu ćwiczeń z prowadzeniem oddechowym, zapewnieniu spokoju, wsparciu w oczyszczaniu dróg oddechowych oraz ścisłym monitorowaniu przy łóżku pacjenta. W ciągu 72 h po ekstubacji nie było konieczności ponownej intubacji, a saturacja tlenem pozostała stabilna. W trakcie następującego po tym 4-tygodniowego okresu obserwacji pacjent utrzymywał spontaniczne oddychanie i nie wymagał inwazyjnej wentylacji mechanicznej.

Porównanie z opisanymi w literaturze przypadkami LOPD leczonymi wentylacją mechaniczną

Przeprowadzono porównanie z literaturą przedmiotu, aby osadzić obecny przypadek w kontekście i wyjaśnić lukę w powtarzalności, której dotyczy niniejszy protokół. Do porównania wybrano dwa opublikowane przypadki LOPD wymagające wsparcia wentylacyjnego, po wykluczeniu jednego wcześniej wymienionego przypadku z powodu niewystarczających informacji demograficznych, genetycznych, wentylacyjnych oraz dotyczących leczenia^40,41. Przypadki porównawcze podsumowano w Tabeli 2.

Przypadek

Płeć

Kraj/pochodzenie etniczne

Wiek (lata)

Wzrost (cm)

Masa (kg)

mutacja(cje) GAA

Wiek w momencie rozpoczęcia pierwszej ERT (lata)

Leczenie/wsparcie

Czas trwania inwazyjnej wentylacji mechanicznej

Literatura

Opublikowany przypadek 1

F

Włochy/Kaukazoid

52

NR

NR

c.-32-13T>G; c.1551+1G>C

52

Intubacja orotrachealna, a następnie tracheotomia; długotrwała wentylacja mechaniczna; ERT z zastosowaniem alglukozydazy alfa; rehabilitacja oddechowa; stopniowe ograniczanie wsparcia wentylacyjnego do użytkowania nocnego; powrót do samodzielnego chodzenia

Długotrwała wentylacja mechaniczna przez 24 h/dobę do momentu poprawy; dokładny czas trwania IMV nie został podany

Menzella i wsp.40

Opublikowany przypadek 2

F

Malezja

28

NR

NR

c.444C>G; c.2238G>C

28

Dieta wysokobiałkowa; ciągła fizjoterapia i wsparcie rehabilitacyjne; ERT, jeśli jest dostępna

9 miesięcy

Liong i wsp.41

Prezentacja przypadku

M

Chiny/etniczni Hanowie

21

NR

NR

Złożone warianty heterozygotyczne GAA: c.-32-13T>G oraz c.2238G>C (p.Trp746Cys)

21

ERT w połączeniu z wielodyscyplinarną rehabilitacją, wsparciem w oczyszczaniu dróg oddechowych, treningiem mięśni oddechowych, progresywną rehabilitacją fizyczną, opieką żywieniową, wsparciem psychologicznym, akupunkturą małżowinową oraz Tai Chi w pozycji siedzącej

Około 1 miesiąc intubacji przed przyjęciem na oddział rehabilitacyjny; pomyślne odłączenie od inwazyjnej wentylacji mechanicznej po wdrożeniu protokołu

Przedstaw raport

Tabela 2: Opublikowane przypadki późnej postaci choroby Pompego wymagające wsparcia wentylacyjnego w porównaniu z obecnym reprezentatywnym pacjentem. Tabela ta podsumowuje charakterystykę demograficzną, wyniki genetyczne, wiek w momencie rozpoczęcia terapii enzymatycznej (ERT), interwencje wspomagające oraz czas trwania inwazyjnej wentylacji mechanicznej w dwóch opublikowanych przypadkach późnej postaci choroby Pompego (LOPD) wymagających wsparcia wentylacyjnego oraz u obecnego reprezentatywnego pacjenta. Jeden wcześniej zidentyfikowany opublikowany przypadek został wykluczony ze względu na niewystarczające informacje demograficzne, genetyczne, wentylacyjne i terapeutyczne do przeprowadzenia strukturalnego porównania. Tabela podkreśla różnice w wymaganiach dotyczących wsparcia oddechowego i podejść do rehabilitacji oraz dostarcza kontekstu klinicznego dla luki w powtarzalności, której dotyczy niniejszy protokół. Skróty: ERT, terapia enzymatyczna; F, kobieta; GAA, gen kwaśnej alfa-glukozydazy; IMV, inwazyjna wentylacja mechaniczna; LOPD, późna postać choroby Pompego; M, mężczyzna; NR, nie podano.

Opublikowane przypadki opisywały wsparcie wentylacyjne, ERT, rehabilitację oddechową, wsparcie żywieniowe lub ogólne leczenie wspomagające; jednak szczegółowe procedury odstawiania respiratora były ograniczone. W przeciwieństwie do nich, niniejszy protokół zapewnia ustrukturyzowane, multidyscyplinarne ramy odstawiania respiratora i rehabilitacji.

Podsumowanie reprezentatywnych wyników

Ogólnie wdrożenie skoordynowanego protokołu ERT i rehabilitacji multidyscyplinarnej wiązało się z przejściem od nieudanych prób SBT i reintubacji w pierwszym miesiącu do pomyślnego SBT, ekstubacji i trwałego odłączenia od inwazyjnej wentylacji mechanicznej do 3. miesiąca. Zmniejszyło się zapotrzebowanie na wsparcie oddechowe, wzrosła tolerancja oddychania spontanicznego, poprawiły się wyniki siły mięśniowej i równowagi, wzrosła podaż żywienia i poziom albuminy w surowicy, wskaźniki psychologiczne pozostały na niskim poziomie, a w ciągu 72 h po ostatecznej ekstubacji nie wystąpiła reintubacja. Wyniki te potwierdzają wykonalność protokołu u tego reprezentatywnego pacjenta z LOPD, choć projekt oparty na pojedynczym przypadku nie pozwala na wyciągnięcie wniosków dotyczących skuteczności lub przyczynowości.

Dostępność danych:

Zanonimizowany zbiór danych stanowiący podstawę tego artykułu jest publicznie dostępny w serwisie Figshare: https://doi.org/10.6084/m9.figshare.30194968.v1

Plik uzupełniający 1. Szczegółowe procedury potwierdzenia diagnostycznego, mechaniki oddychania i monitorowania. Plik ten zawiera rozszerzone procedury potwierdzenia diagnostycznego późnozaczynającej się choroby Pompego, w tym oceny biochemiczne, molekularne i histopatologiczne, a także szczegółowe pomiary mechaniki oddychania, dokumentację wsparcia wentylacyjnego, ocenę tracheostomii, oceny wyjściowe oraz procedury monitorowania. Kliknij tutaj, aby pobrać ten plik.

Plik uzupełniający 2. Szczegółowe procedury podawania, monitorowania i bezpieczeństwa terapii enzymatycznej substytucyjnej. Plik ten opisuje obliczanie dawki alglukozydazy alfa, jej przygotowanie, podawanie, monitorowanie, dostosowanie szybkości wlewu, postępowanie w przypadku reakcji związanych z infuzją, procedury w przypadku anafilaksji, zgłaszanie farmakowigilancji oraz kryteria kontynuacji leczenia. Prosimy kliknąć tutaj, aby pobrać ten plik.

Plik uzupełniający 3. Szczegółowe procedury rehabilitacji fizycznej. Plik ten zawiera rozszerzone procedury rehabilitacji fizycznej, w tym przypisywanie poziomu rehabilitacji, techniki mobilizacji i transferu, progresję treningu oporowego, monitorowanie fizjologiczne, kryteria bezpieczeństwa, progi zakończenia sesji oraz metody ponownej oceny funkcjonalnej. Prosimy kliknąć tutaj, aby pobrać ten plik.

Plik uzupełniający 4. Szczegółowe procedury rehabilitacji oddechowej. Plik ten zawiera szczegółowe procedury dotyczące regulacji respiratora, interwencji w celu udrożnienia dróg oddechowych, treningu mięśni wdechowych, prób spontanicznego oddychania, badania mechaniki oddechowej, technik wspomagania kaszlu, oceny gotowości do ekstubacji oraz monitorowania oddechu. Proszę kliknąć tutaj, aby pobrać ten plik.

Plik uzupełniający 5. Szczegółowe procedury wsparcia żywieniowego i psychologicznego. Plik ten zawiera rozszerzone metody oceny stanu odżywienia, zarządzania żywieniem enteralnym, zapobiegania zespołowi ponownego żywienia, monitorowania czynności jelit, oceny psychologicznej, interwencji doradczych oraz procedury treningu relaksacyjnego. Kliknij tutaj, aby pobrać ten plik.

Plik uzupełniający 6. Szczegółowe procedury akupunktury małżowinowej i Tai Chi. Plik ten opisuje lokalizację punktów akupunktury małżowinowej, procedury nakłuwania, środki ostrożności, wdrożenie ćwiczeń Tai Chi, progresję leczenia, wymagania dotyczące monitorowania oraz procedury postępowania w przypadku wystąpienia zdarzeń niepożądanych. Kliknij tutaj, aby pobrać ten plik.

Plik uzupełniający 7. Szczegółowe procedury ekstubacji, wsparcia poekstubacyjnego oraz postępowania w przypadku niepowodzenia ekstubacji. Plik ten zawiera rozszerzone procedury oceny gotowości do ekstubacji, oddechowego wsparcia po ekstubacji, postępowania w przypadku pogorszenia funkcji oddechowych, klasyfikacji niepowodzeń ekstubacji, reedukacji oddechowej oraz interwencji wspomagających kaszel. Kliknij tutaj, aby pobrać ten plik.

Plik uzupełniający 8. Szczegółowe procedury monitorowania po ekstubacji, obserwacji, dokumentowania wyników i zarządzania dokumentacją. Plik ten zawiera szczegółowe procedury monitorowania po ekstubacji, oceny w ramach obserwacji, wytyczne dotyczące rehabilitacji domowej, definicje wyników, raportowanie odchyleń od protokołu, zarządzanie danymi oraz wymagania dotyczące przechowywania dokumentacji.Kliknij tutaj, aby pobrać ten plik.

Dyskusja

ERT remains the disease-specific biochemical foundation for Pompe disease because it increases exogenous GAA availability and reduces lysosomal glycogen accumulation. However, published evidence demonstrates that the clinical response in LOPD is heterogeneous, and respiratory weakness may remain a major determinant of ventilator dependence despite continued ERT⁴². This observation explains why the present protocol did not treat ERT as a standalone solution. Instead, ERT was combined with respiratory rehabilitation, airway-clearance support, progressive physical rehabilitation, nutritional optimization, psychological support, and adjunctive traditional Chinese medicine-based interventions to address the mechanical, functional, and behavioral factors contributing to ventilator-weaning difficulty.

The respiratory and extubation components of this protocol were intentionally aligned with established neuromuscular disease respiratory-management principles rather than presented as entirely novel Pompe-specific procedures. Current neuromuscular disease guidance emphasizes cough effectiveness, secretion management, non-invasive ventilatory support, respiratory-muscle assessment, and planned post-extubation support in patients with neuromuscular weakness⁴³. The protocol-specific contribution of the present work is therefore not the introduction of new respiratory maneuvers, but the operational integration of these standard elements into a reproducible sequence for a ventilated patient with LOPD, including biochemical treatment, daily multidisciplinary review, objective SBT reassessment, interpretation of RSBI, NIF, and PCF, secretion-control criteria, post-extubation monitoring, and 4-week follow-up.

The findings support the clinical value of a MDT model in this setting. In LOPD, respiratory insufficiency, proximal muscle weakness, malnutrition, secretion retention, anxiety, and treatment fatigue are interdependent rather than isolated problems⁴⁴. A fragmented approach may therefore delay recognition of the factor most responsible for weaning failure at a given time point. In the present protocol, predefined roles, daily bedside huddles, safety thresholds, and measurable milestones allowed the team to adjust respiratory training, physical rehabilitation, nutritional delivery, and psychological support in parallel. This coordinated structure was particularly important after the initial failed SBT because the subsequent management plan addressed respiratory-muscle fatigue, secretion burden, nutritional insufficiency, and anxiety simultaneously rather than sequentially.

The International Classification of Functioning, Disability and Health (ICF) framework is useful for interpreting these changes because successful ventilator weaning is not only a physiological endpoint but also a functional and participation-related outcome⁴⁵. In the present case, improvements in ventilatory tolerance, muscle strength, balance, nutritional status, and confidence in breathing practice supported progression from invasive ventilation to spontaneous respiration and subsequent rehabilitation. The discordance between low GAD-7 and PHQ-9 scores and the patient’s observable transient post-extubation anxiety further suggests that generic screening tools may underestimate situational distress during ventilator liberation. Rather than proposing a completely separate extubation-readiness system for Pompe disease, future work may benefit from developing and evaluating a Pompe-adapted checklist nested within existing neuromuscular disease frameworks and incorporating respiratory mechanics, cough effectiveness, secretion burden, bulbar function, gas exchange, and psychological readiness⁴⁶.

The comparison with published ventilated cases highlights an important reproducibility gap. Previous reports have described ERT, ventilatory support, rehabilitation, nutritional management, or general supportive care, but often provide limited procedural detail regarding the coordination of respiratory training, airway-clearance strategies, SBT reassessment, extubation criteria, and post-extubation monitoring. This limitation is common in rare-disease case-based literature, where incomplete reporting reduces comparability and limits clinical replication⁴⁷. In the revised comparison table, each retained published case is linked to its source reference, and a previously considered case with insufficient demographic, genetic, ventilatory, and treatment information was excluded from structured analysis. This approach improves transparency and avoids overstating the strength of the available evidence.

Several limitations should be acknowledged. The study is based on a single representative case, precluding causal inference and limiting generalizability. The favorable clinical trajectory may have been influenced by baseline muscle reserve, family preference, caregiver support, center-specific expertise, timing of infection control, and continued access to ERT. Future studies should prospectively evaluate this protocol in multicenter cohorts using predefined outcome measures, including ventilator-free days, reintubation within 48–72 h, NIF, PCF, MRC sum score, secretion burden, nutritional delivery, psychological readiness, and patient participation.

Overall, the present case supports the feasibility of a structured multidisciplinary protocol that combines ERT with respiratory, physical, nutritional, psychological, and adjunctive supportive interventions for ventilator liberation in LOPD. Future validation should build upon established neuromuscular disease respiratory-management principles while determining whether protocol standardization can improve reproducibility and clinical outcomes in this rare patient population.

Materiały

Lista materiałów użytych w tym artykule

Nazwa	Firma	Numer katalogowy	Komentarze
0.9% sodium chloride injection	Baxter or equivalent hospital-grade sterile infusion fluid	N/A	Used for dilution of reconstituted alglucosidase alfa before IV infusion.
3 L calibration syringe	Vitalograph	Model 2040; catalog no. 36020	Calibration verification for spirometry or flow/volume measurement equipment.
4-Methylumbelliferyl alpha-D-glucopyranoside	Sigma-Aldrich / Merck	M9766	Fluorogenic substrate for acid alpha-glucosidase activity assay.
Acarbose	Sigma-Aldrich / Merck	A8980	Inhibitor used to suppress maltase-glucoamylase interference during acid alpha-glucosidase activity testing.
Airway management/reintubation kit	Institutional emergency airway cart	N/A	Includes laryngoscope/video laryngoscope, endotracheal tubes, stylet, suction catheter, bag-valve-mask, oxygen source, and emergency medications according to institutional policy.
Alglucosidase alfa	Sanofi / Genzyme	Myozyme or Lumizyme; 50 mg vial	Enzyme replacement therapy; 20 mg/kg IV every 2 weeks; administer with stepwise infusion-rate escalation according to product label.
Antiseptic skin preparation swabs	Embecta / BD	BD Alcohol Swabs; 326895	70% isopropyl alcohol swabs for auricular skin preparation before needle insertion.
Auricular acupuncture needles	TCMSupply	E-S 240901	Single-use sterile auricular acupuncture needles for Shenmen, Heart, and Sympathetic points.
Bag-valve-mask device	Institutional emergency airway cart	N/A	Emergency ventilation support during airway or infusion-related deterioration.
Barthel Index	Publicly available clinical instrument	N/A	Functional status assessment.
Bedside multiparameter monitor	Shenzhen Mindray Bio-Medical Electronics Co., Ltd.	iMEC8	Continuous monitoring of ECG, heart rate, respiratory rate, non-invasive blood pressure, SpO2, and temperature.
Berg Balance Scale	Publicly available clinical instrument	N/A	Balance assessment; score range 0–56.
Biological microscope	MINGHUI	NE710	Muscle-biopsy histopathology review and calibrated image acquisition.
Blood gas analyzer	Radiometer Medical ApS	ABL90 FLEX	Arterial blood gas analysis, including pH, PaO2, PaCO2, bicarbonate, base excess, and lactate.
Borg Category-Ratio 10 scale	Publicly available clinical instrument	N/A	Perceived exertion and dyspnea-related exertional tolerance monitoring.
Bristol Stool Form Scale	Publicly available clinical instrument	N/A	Stool-consistency assessment during bowel-function monitoring.
Case report form / MDT documentation template	Institution-developed form	N/A	Used to record protocol adherence, outcomes, adverse events, deviations, and follow-up data.
EDTA blood collection tube	BD Vacutainer or equivalent	N/A	Peripheral blood collection for leukocyte acid alpha-glucosidase activity testing and GAA molecular testing.
Electric suction apparatus	Yuwell	7A-23D	Airway secretion suction; 20 L/min suction-capacity model suitable for hospital secretion management.
Emergency medications for anaphylaxis	Institutional emergency medication supply	N/A	Includes epinephrine, antihistamine, corticosteroid, bronchodilator, and isotonic crystalloid according to institutional policy.
Enteral feeding pump	MDKMed Medical Technology Co., Ltd.	ME11	Continuous enteral nutrition pump for controlled infusion of nutritional solutions.
Enteral feeding tube	Hospital-approved supplier	N/A	Nasogastric or nasoenteric tube for enteral nutrition when clinically required.
Enteral nutrition formula	Hospital-approved supplier	N/A	Formula selected by dietitian according to energy/protein targets and gastrointestinal tolerance.
GAD-7 questionnaire	Publicly available clinical instrument	N/A	Anxiety assessment.
Genomic DNA extraction kit	QIAGEN	QIAamp DNA Blood Mini Kit; 51104 or 51106	Extraction of genomic DNA from peripheral blood leukocytes for GAA sequencing.
Hand weights	CanDo / Fabrication Enterprises	CanDo vinyl-coated dumbbells	Low-load progressive resistance training for upper-limb strengthening.
High-flow oxygen system	Fisher & Paykel Healthcare	AIRVO 2	Optional post-extubation high-flow nasal oxygen support; flow range 2–60 L/min.
High-protein oral nutritional supplement	Abbott Laboratories	Ensure Plus or equivalent	Oral nutritional support when swallowing and gastrointestinal tolerance permit.
High-throughput sequencing platform	MGI Tech Co., Ltd.	MGISEQ-2000	Sequencing platform used for GAA molecular testing.
Infusion pump	Shenzhen Mindray Bio-Medical Electronics Co., Ltd.	BeneFusion VP1 Ex	Controlled ERT administration through programmable infusion pump.
Inline infusion filter	B. Braun	Sterifix 0.2 μm infusion filter	0.2 μm low-protein-binding in-line filter for alglucosidase alfa administration.
Inspiratory muscle training device	Philips Respironics	Threshold IMT; HS730	Threshold-loading inspiratory muscle trainer for respiratory muscle strengthening.
Intensive Care Unit Mobility Scale	Publicly available clinical instrument	N/A	Mobility-level assessment during rehabilitation.
Invasive ventilator	Shenzhen Comen Medical Instruments Co., Ltd.	COMEN V3A	Used for invasive ventilatory support; representative patient was ventilated in p-SIMV mode on admission.
Low-protein-binding infusion extension set	Becton, Dickinson and Company (BD)	SmartSite Extension Set, 0.2 micron filter; product code 20027E	Low-protein-binding extension set used for filtered IV infusion when available.
Mechanical insufflation-exsufflation device	Philips Respironics	CoughAssist E70; catalog/model 1098163 or 1098159	Used for assisted cough and secretion clearance when cough effectiveness remains inadequate or peak cough flow is severely reduced.
Medical Research Council muscle-strength scale	Publicly available clinical instrument	N/A	Muscle-strength grading and MRC sum score calculation.
Microscope camera	MINGHUI	MHS900 camera	Digital pathology image capture for representative histopathology images.
Non-invasive ventilation system	ResMed	Stellar 150	Used for post-extubation or weaning support when NIV is clinically required.
Nose clip	GVS	Disposable nose clip; product line: Accessories for Spirometry	Used during respiratory mechanics testing when a mouthpiece method is feasible.
Periodic acid-Schiff staining system	Sigma-Aldrich / Merck	395B-1KT	PAS staining of muscle-biopsy sections to demonstrate glycogen accumulation.
PHQ-9 questionnaire	Publicly available clinical instrument	N/A	Depression assessment.
Pulmonary function / peak-flow measurement device	Zhejiang E-Linkcare Meditech Co., Ltd. /	PF680	Used for pulmonary-function assessment and peak expiratory/cough-flow-related measurement; records FVC, FEV1, PEF, and related spirometric parameters.
Respiratory pressure meter for MIP/MEP	XEEK	X1	Used for maximal inspiratory pressure and maximal expiratory pressure measurement.
Respiratory testing mask	Ambu	Ambu Disposable Face Mask; adult size selected according to patient fit	Mask interface for respiratory testing or airway support when a mouthpiece cannot be used.
Respiratory testing mouthpiece	GVS	Ergonomic spirometry mouthpiece; product line: Accessories for Spirometry	Single-patient-use mouthpiece for spirometry or respiratory mechanics testing.
Resistance bands	THERABAND	Professional latex or non-latex resistance bands	Progressive resistance exercises; select resistance level according to therapist assessment.
Richmond Agitation-Sedation Scale	Publicly available clinical instrument	N/A	Sedation and arousal assessment before psychological or functional assessment.
Secure electronic medical record or research-data system	Institutional system	N/A	Used for secure storage of source documents, study records, audit trails, and de-identified research data.
Sharps disposal container	BD or equivalent medical sharps-disposal supplier	N/A	Rigid puncture-resistant sharps container for immediate disposal of used acupuncture needles.
Stable armless chair	Hospital-approved rehabilitation equipment supplier	N/A	Used for 30-s chair-stand test; chair height approximately 43–45 cm.
Sterile water for injection	Baxter or equivalent hospital-grade sterile diluent	N/A	Used for reconstitution of alglucosidase alfa according to manufacturer’s instructions.
Stopwatch/timer	Hospital-approved supplier	N/A	Used for SBT timing, respiratory-training intervals, exercise sessions, Tai Chi sessions, and monitoring intervals.
Tai Chi instructional materials	Dr. Paul Lam Tai Chi Productions or institution-developed seated Tai Chi protocol	N/A	Used to standardize seated Tai Chi movement sequence and breathing coordination.
Transfer aid	Arjo	Sara Stedy	Sit-to-stand and transfer support during early mobilization and standing practice.
Whole-chest oscillation sputum-clearance device	Changzhou Siya Medical Device Co., Ltd. / Yasi	YSQ01B	Whole-chest oscillation airway-clearance device used for secretion mobilization and sputum clearance.