Cardiopulmonary exercise test to quantify enzyme replacement response in pediatric Pompe disease

Bar‐Yoseph, Ronen; Mandel, Hanna; Mainzer, Gur; Gur, Michal; Tal, Galit; Shalloufeh, George; Bentur, Lea

doi:10.1002/ppul.23830

Cited by 5 publications

(10 citation statements)

References 31 publications

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“…The reported data on the acute and long-term effects of ERT on CPET parameters is especially in IOPD. The safety of exercise and CPET was demonstrated in LOPD [10,24], and we recently demonstrated the feasibility and safety of CPET in five pediatric Pompe disease patients [11].…”

Section: Discussionmentioning

confidence: 89%

“…Patients' exercise limitations contribute significantly to the patients' perception of impaired well-being. While the focus on metabolic/functional capacity (e.g., cardiopulmonary exercise testing, CPET) in adult late-onset Pompe disease (LOPD) is growing rapidly, the data on pediatric IOPD patients are scarce [10,11]. Our aim was to provide a more objective quantification of the acute and long-term effect of ERT on exercise capacity and explore the possible relationship between the blood enzyme level and exercise capacity.…”

Section: Introductionmentioning

confidence: 99%

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Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease

Bar‐Yoseph¹,

Tal

Dumin

et al. 2021

JPM

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Background: Enzyme replacement therapy (ERT) with alglucosidase alfa improves the prospect of patients with infantile-onset Pompe disease (IOPD). However, a progressive decline has been reported. Objective quantification of the response to ERT when assessing newer strategies is warranted. Methods: This combined retrospective-prospective study assessed the acute and long-term effects of ERT on exercise in IOPD patients. Evaluation included cardiopulmonary exercise testing (CPET), 6-min walking test (6MWT), spirometry, motor function test (GMFM-88) and enzyme blood levels. Results: Thirty-four CPETs (17 pre- and 17 two days-post ERT) over variable follow-up periods were performed in four patients. Two days following ERT, blood enzyme levels increased (median, 1.22 and 10.15 μmol/L/h (p = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO2 were unchanged. Long-term evaluations showed stabilization in young patients but progressive deterioration in adolescents. Clinical deterioration was associated with more pronounced deterioration in peak VO2 followed in the decreasing order by 6MWD, FVC and GMFM-88. Conclusions: The peak VO2 and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO2 and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease

Bar‐Yoseph¹,

Tal

Dumin

et al. 2021

JPM

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“…Pompe Group Size Calculation : The only previous study investigating exercise capacity in children with Pompe disease includes five patients and shows that children with Pompe have a PeakVO 2 between 11.1 and 40.2 ml/kg/min, with a 75%ile of 37.7 ml/kg/min ( 14 ). We have chosen to use the 75%ile to calculate the group size, as we think this value of PeakVO 2 is closest to the PeakVO 2 of our own Pompe children population.…”

Section: Methods and Analysismentioning

confidence: 99%

“…Despite ERT treatment, many Pompe disease patients eventually become ventilator or wheelchair dependent. It is known that patients with Pompe disease has a decreased exercise capacity which is not caused by impaired skeletal muscle glycogenetic capacity but rather by muscle weakness and wasting ( 14 ). A study by van den Berg et al published in 2015 showed that exercise training in adult patients with late onset Pompe disease might be a safe and effective adjuvant therapy for ERT ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions—A Randomized Cross Over Trial

et al. 2022

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Introduction: Physical activity is associated with many physiological and psychological health benefits across the lifespan. Children with a chronic disease often have lower levels of daily physical activity, and a decreased exercise capacity compared to healthy peers. In order to learn more about limitations for physical activity, we investigate children with four different chronic diseases: children with a Fontan circulation, children with Broncho Pulmonary Dysplasia (BPD), Pompe disease and inflammatory bowel disease (IBD). Each of these diseases is likely to interfere with physical activity in a different way. Knowing the specific limitations for physical activity would make it possible to target these, and increase physical activity by a personalized intervention. The aim of this study is to first investigate limitations for physical activity in children with various chronic diseases. Secondly, to measure the effects of a tailored exercise intervention, possibly including a personalized dietary advice and/or psychological counseling, on exercise capacity, endurance, quality of life, fatigue, fear for exercise, safety, muscle strength, physical activity levels, energy balance, and body composition.Methods and Analysis: This randomized crossover trial will aim to include 72 children, aged 6–18 years, with one of the following diagnosis: a Fontan circulation, BPD, Pompe disease and IBD. Eligible patients will participate in the 12-week tailored exercise intervention and are either randomized to start with a control period or start with the intervention. The tailored 12-week exercise interventions, possibly including a personalized dietary advice and/or psychological counseling, will be designed based on the found limitations for physical activity in each disease group during baseline measurements by the Rotterdam Exercise Team. Effects of the tailored training interventions will be measured on the following endpoints: exercise capacity (measured by cardiopulmonary exercise test), endurance, physical activity levels, muscle strength, quality of life, fatigue, fear for exercise, disease activity, cardiac function (in children with a Fontan circulation), energy balance, and body composition.Ethics and Dissemination: Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval was obtained.Trial Registration Number: NL8181, https://www.trialregister.nl/trial/8181.

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“…Ko [12] estimated MCID ranges for GMFM-88 in pediatric CP with a distribution-based approach grounded on effect size (change divided by standard deviation [SD] at enrollment) of 6 months' physical therapy, and determined its correlation to changes in GMFM-66 and Pediatric Evaluation of Disability Inventory mobility (PEDI) scores. GMFM-88 was developed [18] and validated [11] for CP, a nonprogressive motor disability, yet also has precedent (though not yet validation) for use in children and adults with Pompe disease [19,20]. It complements the infant-specific motor measures used in the pivotal IOPD trials of 160L alglucosidase alfa [21,22].…”

Section: Introductionmentioning

confidence: 99%

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

Duong

Kishnani

Haack

et al. 2022

Journal of Neuromuscular Diseases

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Background: ADVANCE (NCT01526785) presented an opportunity to obtain a more nuanced understanding of motor function changes in treatment-experienced children with Pompe disease receiving 4000L-production-scale alglucosidase alfa for 52 weeks. Objective: To estimate minimal detectable change (MDC) and effect size on Gross Motor Function Measure-88 (GMFM-88) after 52 weeks of 4000L alglucosidase alfa (complete data N = 90). Methods: The GMFM-88 mean total % score changes, MDC, and effect size were analyzed post hoc by Pompe Motor Function Level at enrollment, age groups at enrollment, and fraction of life on pre-study 160L-production-scale alglucosidase alfa. Results: Overall, participants aged < 2 years surpassed MDC at Week 52 (change [mean±standard deviation] 21.1±14.1, MDC range 5.7–13.3, effect size 1.1), whereas participants aged≥2 years did not attain this (change –0.9±15.3, MDC range 10.8–25.2, effect size –0.03). In participants aged < 2 years, improvements surpassed the MDC for walkers (change 17.1±13.3, MDC range 3.0–6.9, effect size 1.7), supported standers (change 35.2±18.0, MDC range 5.9–13.7, effect size 1.8) and sitters (change 24.1±12.1, MDC range 2.6–6.2, effect size 2.7). Age-independent MDC ranges were only attained by walkers (change 7.7±12.3, MDC range 6.4–15.0, effect size 0.4) and sitters (change 9.9±17.2, MDC range 3.3–7.7, effect size 0.9). Conclusions: These first GMFM-88 minimal-detectable-change estimates for alglucosidase alfa-treated Pompe disease offer utility for monitoring motor skills. Trial registration: ClinicalTrials.gov; NCT01526785; Registered 6 February 2012; https://clinicaltrials.gov/ct2/show/NCT01526785

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Cardiopulmonary exercise test to quantify enzyme replacement response in pediatric Pompe disease

Cited by 5 publications

References 31 publications

Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease

Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease

Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions—A Randomized Cross Over Trial

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort

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