JMIR Publications

ABSTRACT

Background:

Introduction: Dyspnea is a prevalent symptom for individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and generalized hypermobility spectrum disorder (G-HSD). The characteristics and contributors to dyspnea in hEDS/G-HSD have not been well elucidated. One known contributor to dyspnea is respiratory muscle weakness. The feasibility and effectiveness of inspiratory muscle training (IMT) in combination with standard of care rehabilitation (aerobic, resistance, neuromuscular stabilization, and balance and proprioception exercises) to improve respiratory muscle strength and related patient-reported outcomes in hEDS/G-HSD patients have not been evaluated.

Objective:

Objectives: 1) To evaluate dyspnea, respiratory muscle strength, and patient-reported outcome measures (PROMs) in hEDS/G-HSD compared to healthy controls, and 2) to assess the feasibility of a randomized control trial of IMT and standard of care rehabilitation to improve respiratory muscle strength, exercise capacity and PROMs compared to standard of care rehabilitation in hEDS/G-HSD.

Methods:

Methods:

The study will include 34 hEDS/G-HSD participants from the EDS rehabilitation program at Toronto General Hospital and 17 healthy, age-sex matched controls for comparison of respiratory muscle structure and function and PROMs. After baseline assessments, hEDS/G-HSD participants will be randomized into IMT combined with EDS standard of care rehabilitation (intervention group) versus standard of care rehabilitation (usual care) for 8 weeks. The intervention group will be prescribed IMT in the home environment using the POWERbreathe®K5 IMT device. IMT will comprise of 2 daily sessions, 5 days per week of 30 breaths, with IMT progressing from 20% to 60% of baseline maximal inspiratory pressure (MIP) over an 8-week period. Feasibility will be assessed through rates of recruitment, attrition, adherence, and adverse events, as well as participant satisfaction. The primary pilot outcome will be MIP change over an 8-week period in hEDS/G-HSD. Secondary outcomes will include evaluation of dyspnea (Medical Research Council Scale and 18-point Qualitative Dyspnea Descriptors), diaphragmatic thickening fraction with ultrasound, respiratory muscle endurance, pulmonary function including oscillometry, pre-frontal cortical activity using functional near-infrared spectroscopy and aerobic capacity during cardiopulmonary exercise testing, quality of life (Short Form-36), and scores from the depression, anxiety and stress scale (DASS-21). These measures will also be performed once in healthy controls for comparison of normative values. Multivariable regression will be used to assess the contributors to dyspnea. Paired-t-tests will be utilized to assess the change in MIP and secondary measures with 8 weeks of IMT.

Results:

Results:

Study recruitment began in August 2021, with several disruptions due to COVID-19, and is expected to be completed by December 2023.

Conclusions:

Conclusion: This study will provide a better understanding of the factors associated with dyspnea and the feasibility and effectiveness of IMT combined with standard of care rehabilitation. IMT may be a novel therapeutic strategy to improve respiratory muscle function and patient reported outcomes in individuals with hEDS/G-HSD. Clinical Trial: ClinicalTrials.gov (NCT04972565)