Modeling of changes in forced vital capacity and late-onset Pompe disease related outcomes

IntroductionObesity can lead to a late-onset nonallergic (LONA) form of asthma for reasons that are not understood. We sought to determine whether this form of asthma is characterised by any unique physiological features.MethodsSpirometry, body plethysmography, multiple breath nitrogen washout (MBNW) and methacholine challenge were performed in four subject groups: Lean Control (n=11), Lean Asthma (n=11), Obese Control (n=11) and LONA Obese Asthma (n=10). The MBNW data were fitted with a novel computational model that estimates functional residual capacity (FRC), dead space volume (VD), the coefficient of variation of regional specific ventilation (CV,V′E) and a measure of structural asymmetry at the level of the acinus (sacin).ResultsBody mass index and waist circumference values were similar in both obese groups, and significantly greater than in lean asthmatic individuals and controls. Forced vital capacity was significantly lower in the LONA Asthma group compared with the other groups (p<0.001). Both asthma groups exhibited similar hyperresponsiveness to methacholine. FRC was reduced in the Obese LONA Asthma group as measured by MBNW, but not in obese controls, whereas FRC was reduced in both obese groups as measured by plethysmography. VD, CV,V′E and sacin were not different between groups.ConclusionsChronic lung compression characterises all obese subjects, as reflected by reduced plethysmographic FRC. Obese LONA asthma is characterised by a reduced ability to recruit closed lung units, as seen by reduced MBNW FRC, and an increased tendency for airway closure as seen by a reduced forced vital capacity.

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Forced vital capacity and cross-domain late-onset Pompe disease outcomes: an individual patient-level data meta-analysis

Journal of Neurology ◽

10.1007/s00415-019-09401-1 ◽

2019 ◽

Vol 266 (9) ◽

pp. 2312-2321

Author(s):

Kenneth I. Berger ◽

Steve Kanters ◽

Jeroen P. Jansen ◽

Andrew Stewart ◽

Susan Sparks ◽

...

Keyword(s):

Forced Vital Capacity ◽

Vital Capacity ◽

Late Onset ◽

Meta Analysis ◽

Patient Level Data ◽

Individual Patient Level ◽

Patient Level ◽

Cross Domain ◽

Disease Outcomes ◽

Level Data

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Chest MRI to diagnose early diaphragmatic weakness in Pompe disease

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01627-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Laurike Harlaar ◽

Pierluigi Ciet ◽

Gijs van Tulder ◽

Alice Pittaro ◽

Harmke A. van Kooten ◽

...

Keyword(s):

Supine Position ◽

Forced Vital Capacity ◽

Pompe Disease ◽

Respiratory Function ◽

Vital Capacity ◽

Healthy Controls ◽

Irreversible Damage ◽

The Mean ◽

Diaphragmatic Weakness ◽

Anterior Posterior

Abstract Background In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. Methods Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior–posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. Results We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior–posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. Conclusions Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.

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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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Quantifying Vocal Power: Correlation of Whole-Body Anaerobic Power to Vocal Function Measures

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-20-00110 ◽

2020 ◽

Vol 63 (8) ◽

pp. 2597-2608

Author(s):

Emily N. Snell ◽

Laura W. Plexico ◽

Aurora J. Weaver ◽

Mary J. Sandage

Keyword(s):

Fundamental Frequency ◽

Forced Vital Capacity ◽

Vital Capacity ◽

Anaerobic Power ◽

Performance Outcomes ◽

Sound Level ◽

Whole Body ◽

Vocal Function ◽

Laryngeal Diadochokinesis ◽

High Sound

Purpose The purpose of this preliminary study was to identify a vocal task that could be used as a clinical indicator of the vocal aptitude or vocal fitness required for vocally demanding occupations in a manner similar to that of the anaerobic power tests commonly used in exercise science. Performance outcomes for vocal tasks that require rapid acceleration and high force production may be useful as an indirect indicator of muscle fiber complement and bioenergetic fitness of the larynx, an organ that is difficult to study directly. Method Sixteen women (age range: 19–24 years, M age = 22 years) were consented for participation and completed the following performance measures: forced vital capacity, three adapted vocal function tasks, and the horizontal sprint test. Results Using a within-participant correlational analyses, results indicated a positive relationship between the rate of the last second of a laryngeal diadochokinesis task that was produced at a high fundamental frequency/high sound level and anaerobic power. Forced vital capacity was not correlated with any of the vocal function tasks. Conclusions These preliminary results indicate that aspects of the laryngeal diadochokinesis task produced at a high fundamental frequency and high sound level may be useful as an ecologically valid measure of vocal power ability. Quantification of vocal power ability may be useful as a vocal fitness assessment or as an outcome measure for voice rehabilitation and habilitation for patients with vocally demanding jobs.

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