Side-Alternating Vibration Training Improves Muscle Performance in a Patient with Late-Onset Pompe Disease

Side-alternating vibration training (SAVT) was used for 15 weeks in a patient with Late-onset Pompe disease who had never used enzyme replacement or chaperone therapy. Prior to the use of SAVT, the patient had experienced declining muscle performance and her 6-minute walk distance decreased from 210 to 155 metres in 6 months. After SAVT, her 6-minute walk distance increased 70% from 166 to 282 metres, muscle jumping power increased by 64% from 83 to 166 watts, isometric knee extensor strength increased 17% from 38 to 44 Nm, and she achieved a more normal pattern of ankle, knee, and joint kinematics and kinetics. Her functional ability measured through the Rotterdam 9-item score was unchanged at 19/36. There were no elevations in serum creatine kinase or lactate. This is the first report, to our knowledge, of a performance improvement in a patient with Pompe disease using SAVT.

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Respiratory manifestations in late-onset Pompe disease: a case series conducted in Brazil

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562015000000343 ◽

2017 ◽

Vol 43 (1) ◽

pp. 54-59 ◽

Cited By ~ 2

Author(s):

Bruna de Souza Sixel ◽

Luanda Dias da Silva ◽

Nicolette Celani Cavalcanti ◽

Glória Maria Cardoso de Andrade Penque ◽

Sandra Lisboa ◽

...

Keyword(s):

Symptom Onset ◽

Pompe Disease ◽

Late Onset ◽

Case Series ◽

Definitive Diagnosis ◽

Walk Distance ◽

Enzyme Replacement ◽

Initial Symptoms ◽

Minute Walk Distance ◽

Minute Walk

ABSTRACT Objective: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy. Methods: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability. Analyses were carried out using frequencies, medians, minimum values, and maximum values. Results: Six patients were included in the study. The median age at symptom onset was 15 years (range, 13-50 years), and the median age at diagnosis was 39.5 years (range, 10-64 years). The median time from symptom onset to diagnosis was 8 years (range, 0-45 years). In all cases, the initial manifestation of the disease had been motor weakness. The median FVC in percentage of the predicted value (FVC%) in the sitting and supine positions was 71.0% (range, 22.9-104.6%) and 58.0% (range, 10.9-106.9%), respectively. The median ΔFVC% was 24.5% (range, −4.59 to 52.40%).The median six-minute walk distance was 391.7 m (range, 97-702 m) . Conclusions: In this case series, the time from symptom onset to diagnosis was long. Although respiratory signs or symptoms were not the initial manifestations of the disease, 66.7% of the patients showed reduced FVC% in the sitting and supine positions at diagnosis.

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Use of the patient-reported outcomes measurement information system (PROMIS®) to assess late-onset Pompe disease severity

Journal of Patient-Reported Outcomes ◽

10.1186/s41687-020-00245-2 ◽

2020 ◽

Vol 4 (1) ◽

Author(s):

Melodi Harfouche ◽

Priya S. Kishnani ◽

Eva Krusinska ◽

Jamie Gault ◽

Sheela Sitaraman ◽

...

Keyword(s):

Clinical Outcome ◽

Outcome Measures ◽

Pompe Disease ◽

Patient Reported Outcomes ◽

Vital Capacity ◽

Late Onset ◽

Walk Distance ◽

Patient Reported ◽

Minute Walk Distance ◽

Minute Walk

Abstract Background Patient-Reported Outcomes provide an opportunity for patients to establish dialogue with pharmaceutical or biotechnology companies about their health conditions without interpretation by a clinician or anyone else. However, Patient-Reported Outcomes that can be widely applicable for use in patient-focused drug development or clinical trial designs are not yet validated for all diseases. The aim of this study report was to provide supportive evidence of the construct and content validity of selected Patient-Reported Outcomes Measurement Information System (PROMIS®) questionnaires compared with other disease-relevant clinical outcome measures, including the 6-Minute Walk Distance, forced vital capacity, and Manual Muscle Test, in late-onset Pompe disease and to provide supportive evidence that the selected PROMIS measures are relevant and important to these patients. Methods Thirty patients with late-onset Pompe disease completed five PROMIS questionnaires that were chosen based on patient and provider feedback, along with discussion with key opinion leaders who are experts in Pompe disease. The Amicus Pompe Patient Advisory Board also provided patient experience feedback using the PROMIS questionnaires. Clinical outcome measures (6-Minute Walk Distance, forced vital capacity, and Manual Muscle Test) were collected at the Duke University Pompe Disease Clinical Research Program during a single visit. Results The Patient Advisory Board rated the questionnaires as representative of an unmet need. Correlation data demonstrated moderate to strong correlations of PROMIS questionnaires with the specified clinical outcome measures (6-Minute Walk Distance, forced vital capacity, and Manual Muscle Test). These data supported the construct and content validity of the PROMIS questionnaires because they confirmed the motor signs and symptoms of functional disability observed in patients with Pompe disease. Conclusions The correlations indicate that the clinical outcome measures assess important concepts related to patient-reported experiences. The Patient Advisory Board findings suggest that the selected PROMIS questionnaires are meaningful and address important concepts to patients with Pompe disease. The data were collected from a small number of patients at a single time point; further studies are needed with additional PROMIS questionnaires, which should include measures of motor function and health-related quality of life, in a larger number of patients followed up longitudinally.

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The Utility of the Sit-to-Stand Test for Inpatients in the Acute Hospital Setting After Lung Transplantation

Physical Therapy ◽

10.1093/ptj/pzaa057 ◽

2020 ◽

Vol 100 (7) ◽

pp. 1217-1228

Author(s):

Benjamin J Tarrant ◽

Rebecca Robinson ◽

Caitlin Le Maitre ◽

Megan Poulsen ◽

Monique Corbett ◽

...

Keyword(s):

Lung Transplantation ◽

Interrater Reliability ◽

Intraclass Correlation ◽

Hospital Setting ◽

Knee Extensor ◽

Effect Sizes ◽

Walk Distance ◽

Sit To Stand ◽

Minute Walk Distance ◽

Minute Walk

Abstract Objective Measurement of physical function is important to guide physical therapy for patients post-lung transplantation (LTx). The Sit-to-Stand (STS) test has proven utility in chronic disease, but psychometric properties post-LTx are unknown. The study aimed to assess reliability, validity, responsiveness, and feasibility of the 60-second STS post-LTx. Methods This was a measurement study in 62 inpatients post-LTx (31 acute postoperative; 31 medical readmissions). Interrater reliability was assessed with 2 STS tests undertaken by different assessors at baseline. Known group validity was assessed by comparing STS repetitions in postoperative and medical groups. Content validity was assessed using comparisons to knee extensor and grip strength, measured with hand-held dynamometry. Criterion validity was assessed by comparison of STS repetitions and 6-minute walk distance postoperatively. Responsiveness was assessed using effect sizes over inpatient admission. Results Median (interquartile range) age was 62 (56–67) years; time post-LTx was 5 (5–7) days postoperative and 696 (244–1849) days for medical readmissions. Interrater reliability was excellent (intraclass correlation coefficient type 2,1 = 0.96), with a mean learning effect of 2 repetitions. Repetitions were greater for medical at baseline (mean 18 vs 8). More STS repetitions were associated with greater knee extensor strength (postoperative r = 0.57; medical r = 0.47) and 6-minute walk distance (postoperative r = 0.68). Effect sizes were 0.94 and 0.09, with a floor effect of 23% and 3% at baseline (postoperative/medical) improving to 10% at discharge. Patients incapable of attempting a STS test were excluded, reducing generalizability to critical care. Physical rehabilitation was not standardized, possibly reducing responsiveness. Conclusions The 60-second STS demonstrated excellent interrater reliability and moderate validity and was responsive to change postoperatively. Impact The 60-second STS represents a safe, feasible functional performance tool for inpatients post-LTx. Two tests should be completed at each time point.

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The Impact of Yoga on Inspiratory Muscle Performance in Veterans with COPD: A Pilot Study

International Journal of Yoga Therapy ◽

10.17761/2021-d-19-00066 ◽

2021 ◽

Author(s):

Nicole D. DeLuca ◽

Jackeline P. Vajta Gomez ◽

Isabel Vital ◽

Lawrence P. Cahalin ◽

Michael A. Campos

Keyword(s):

Muscle Weakness ◽

Depression Scale ◽

Inspiratory Muscle ◽

Muscle Performance ◽

Inspiratory Pressure ◽

Anxiety And Depression ◽

Maximal Inspiratory Pressure ◽

Walk Distance ◽

Minute Walk Distance ◽

Minute Walk

Abstract Chronic obstructive pulmonary disease (COPD) causes respiratory muscle weakness that leads to disabling dyspnea and poor functional performance. Therapies are often geared to improve inspiratory muscle performance. Yoga has been shown to improve exercise capacity, quality of life, and some pulmonary function measures in COPD, but little research has examined the effects of yoga training on inspiratory muscle performance. The purpose of this study was to investigate the effects of yoga training on inspiratory muscle performance in military veterans using the Test of Incremental Respiratory Endurance (TIRE). A prospective pilot study examined a 6-week yoga training program consisting of asana (poses) and pranayama (controlled breathing). Subjects had baseline inspiratory muscle weakness. The TIRE measured inspiratory muscle performance via the PrO2 device, providing maximal inspiratory pressure, sustained maximal inspiratory pressure, and inspiratory duration. Secondary measures included 6-minute walk distance, St. George Respiratory Questionnaire, Hospital Anxiety and Depression Scale, and spirometry. Mean age and BMI of subjects were 67 ± 3.6 years and 20.7 ± 3.3, respectively. The majority of subjects had severe (28.7%) or very severe (57.1%) COPD. Statistically significant improve m e n t s were seen in maximal inspiratory pressure (39.0 ± 14.1 cmH2O to 56.4 ± 20.6 cmH2O) and sustained maximal inspiratory pressure (244.1 ± 100.6 PTU to 308.1 ± 121.2 PTU). No statistically significant improvements we re observed in 6-minute walk distance, St. George Respiratory Questionnaire, Hospital Anxiety and Depression Scale, or spirometry. Yoga training has the potential in improve inspiratory muscle performance in veterans with severe to very severe COPD who present with inspiratory muscle weakness. This is of importance because improving inspira-tory muscle performance has been shown to improve COPD outcomes.

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Faculty Opinions recommendation of Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717963542.793465451 ◽

2012 ◽

Author(s):

Luke Howard

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Walk Distance ◽

End Point ◽

Pulmonary Arterial ◽

Minute Walk Distance ◽

Minute Walk

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Characteristics and health status of patients with and without confirmed HFpEF

European Heart Journal ◽

10.1093/ehjci/ehaa946.3139 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Deaton ◽

F Forsyth ◽

J Mant ◽

D Edwards ◽

R Hobbs ◽

...

Keyword(s):

Quality Of Life ◽

Primary Care ◽

Cohort Study ◽

Health Status ◽

Functional Impairment ◽

Funding Source ◽

Walk Distance ◽

Minute Walk Distance ◽

Minute Walk

Abstract Aims Patients with heart failure with preserved ejection fraction (HFpEF) are usually older and multi-morbid and diagnosis can be challenging. The aims of this cohort study were to confirm diagnosis of HFpEF in patients with possible HFpEF recruited from primary care, to compare characteristics and health status between those with and without HFpEF, and to determine factors associated with health status in patients with HFpEF. Methods Patients with presumed HFpEF were recruited from primary care practices and underwent clinical assessment and diagnostic evaluation as part of a longitudinal cohort study. Health status was measured by Montreal Cognitive Assessment (MOCA), 6-minute walk test, symptoms, and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and quality of life (QoL) by EQ-5D-5L visual analogue scale (VAS). Results 151 patients (mean age 78.5±8.6 years, 40% women, mean EF 56% + 9.4) were recruited and 93 (61.6%) were confirmed HFpEF (those without HFpEF had other HF and cardiac diagnoses). Patients with and without HFpEF did not differ by age, MOCA, blood pressure, heart rate, NYHA class, proportion with atrial fibrillation, Charlson Comorbidity Index, or NT-ProBNP levels. Patients with HFpEF were more likely to be women, overweight or obese, frail, and to be more functionally impaired by 6 minute walk distance and gait speed than those without. Although not statistically significant, patients with HFpEF had clinically significant differences (>5 points) on the physical limitations, symptom burden and clinical summary subscales of the KCCQ, but did not differ by other subscales or by EQ-5D-5L VAS (70±17 vs 73±19, p=0.385). More patients with HFpEF reported daytime dyspnoea (63% vs 46%, p=0.035) and fatigue (81% vs 61%, p=0.008), but not other symptoms compared to those without HFpEF. For both groups BMI was moderately negatively correlated with KCCQ subscale scores, and 6 minute walk distance was positively correlated with KCCQ subscales. Conclusions Nearly 40% were not confirmed as HFpEF indicating the challenges of diagnosis. Patients with confirmed HFpEF differed by sex, overweight/obesity, frailty, functional impairment, and symptoms but not by age or comorbidities from those without HFpEF. These differences were reflected in some subscale scores of the KCCQ, but not how patients reported their quality of life on the KCCQ QoL subscale and EQ-5D-5L VAS. Older patients with HFpEF reported relatively high QoL despite poor health status by functional impairment, frailty and symptoms. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research School of Primary Care Research

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Predictors of reduced 6-minute walk distance after COVID-19: a cohort study in Mexico

Pulmonology ◽

10.1016/j.pulmoe.2021.03.004 ◽

2021 ◽

Author(s):

Alyson W. Wong ◽

Stephanie López-Romero ◽

Esperanza Figueroa-Hurtado ◽

Saul Vazquez-Lopez ◽

Kathryn M. Milne ◽

...

Keyword(s):

Cohort Study ◽

Walk Distance ◽

Minute Walk Distance ◽

Minute Walk

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42 Is Mitochondrial Function Measured by 31P Magnetic Resonance Spectroscopy Associated with Physical Performance in Older People with Functional Impairment?

Age and Ageing ◽

10.1093/ageing/afab030.03 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

pp. i12-i42

Author(s):

R R Chungath ◽

M D Witham ◽

C L Clarke ◽

A Hutcheon ◽

S Gandy ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Older People ◽

Physical Performance ◽

Functional Impairment ◽

Resonance Spectroscopy ◽

Walk Distance ◽

31P Magnetic Resonance Spectroscopy ◽

Minute Walk Distance ◽

Minute Walk

Abstract Background Mitochondrial dysfunction has been proposed as a therapeutic target to improve muscle strength and endurance, but the contribution that mitochondrial dysfunction makes to impaired skeletal muscle performance in older people remains unclear. We studied the relationship between phosphocreatine recovery rate (a measure of skeletal muscle mitochondrial function) and physical performance in older people. Methods We analysed data from the Allopurinol in Functional Impairment (ALFIE) trial. Participants aged 65 and over, who were unable to walk 400 m in six minutes, underwent 31P magnetic resonance spectroscopy of the calf after exercise at baseline and at 20 weeks follow up. The phosphocreatine recovery half-life time (t-half) was derived as a measure of mitochondrial function. Participants also undertook the 6-minute walk distance, the Short Physical Performance Battery test (SPPB), and had muscle mass measured using bio-impedance analysis. Bivariate correlations and multivariable regression analyses were conducted to determine associations between t-half and baseline factors. Results One hundred and seventeen people underwent baseline 31P magnetic resonance spectroscopy, mean age 80.4 years (SD 6.0); 56 (48%) were female. Mean 6-minute walk was 291 m (SD 80) and mean SPPB score was 8.4 (SD 1.9). T-half was significantly correlated with SPPB score (r = 0.22, p = 0.02) but not with 6-minute walk distance (r = 0.10, p = 0.29). In multivariable linear regression, muscle mass and weight, but not t-half, were independently associated with SPPB score and with 6-minute walk distance. The change in t-half between baseline and 20 weeks was not significantly associated with the change in SPPB (r = 0.03, p = 0.79) or with the change in 6-minute walk distance (r = −0.11, p = 0.28). Conclusion Muscle mass, but not phosphocreatine recovery time, was associated with Short Physical Performance Battery score and 6-minute walk distance in this cohort of older people with functional impairment.

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Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

International Journal of Molecular Sciences ◽

10.3390/ijms22073625 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3625

Author(s):

Filomena Napolitano ◽

Giorgia Bruno ◽

Chiara Terracciano ◽

Giuseppina Franzese ◽

Nicole Piera Palomba ◽

...

Keyword(s):

Pompe Disease ◽

Rare Variants ◽

Clinical Symptoms ◽

Late Onset ◽

Respiratory Muscles ◽

Autosomal Recessive Disorder ◽

Compound Heterozygous ◽

Enzyme Replacement ◽

Whole Exome ◽

Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

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