@Article{info:doi/10.2196/44832,
author="Rozenberg, Dmitry
and Al Kaabi, Noor
and Camacho Perez, Encarna
and Nourouzpour, Sahar
and Lopez-Hernandez, Laura
and McGillis, Laura
and Goligher, Ewan
and Reid, W Darlene
and Chow, Chung-Wai
and Ryan, Clodagh M
and Kumbhare, Dinesh
and Huszti, Ella
and Champagne, Kateri
and Raj, Satish
and Mak, Susanna
and Santa Mina, Daniel
and Clarke, Hance
and Mittal, Nimish",
title="Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Generalized Hypermobility Spectrum Disorder: Protocol for a Pilot and Feasibility Randomized Controlled Trial",
journal="JMIR Res Protoc",
year="2023",
month="Mar",
day="20",
volume="12",
pages="e44832",
keywords="Ehlers-Danlos Syndrome; generalized hypermobility spectrum disorders; inspiratory muscle training; rehabilitation; exercise; mobile phone",
abstract="Background: Dyspnea is a prevalent symptom in individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and generalized hypermobility spectrum disorder (G-HSD), yet its contributors have not been identified. 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) in improving respiratory muscle strength and patient-reported outcomes in patients with hEDS or G-HSD have not been evaluated. Objective: This study aims to evaluate dyspnea, respiratory muscle strength, and patient-reported outcome measures (PROMs) in hEDS or G-HSD compared with healthy controls and to assess the feasibility of a randomized controlled trial of IMT and standard-of-care rehabilitation for improving respiratory muscle strength, exercise capacity, and PROMs compared with standard-of-care rehabilitation in hEDS and G-HSD. Methods: The study will include 34 participants with hEDS or G-HSD and 17 healthy, age- and sex-matched controls to compare respiratory muscle structure and function and PROMs. After baseline assessments, participants with hEDS or G-HSD will be randomized into the intervention group and provided IMT combined with Ehlers-Danlos Syndrome standard-of-care rehabilitation or into the usual care group, and provided only standard-of-care rehabilitation for 8 weeks. The intervention group will be prescribed IMT in their home environment using the POWERbreathe K5 IMT device (POWERbreathe International Ltd). IMT will comprise 2 daily sessions of 30 breaths for 5 days per week, with IMT progressing from 20{\%} to 60{\%} of the baseline maximal inspiratory pressure (MIP) over an 8-week period. Feasibility will be assessed through rates of recruitment, attrition, adherence, adverse events, and participant satisfaction. The primary pilot outcome is MIP change over an 8-week period in hEDS or G-HSD. Secondary outcomes will include the evaluation of dyspnea using Medical Research Council Scale and 18-point qualitative dyspnea descriptors; diaphragmatic thickening fraction using ultrasound; respiratory muscle endurance; pulmonary function; prefrontal cortical activity using functional near-infrared spectroscopy; aerobic capacity during cardiopulmonary exercise testing; quality of life using Short Form-36; and scores from the Depression, Anxiety, and Stress scale-21. These measures will also be performed once in healthy controls to compare normative values. Multivariable regression will be used to assess the contributors to dyspnea. Paired 2-tailed t tests will be used to assess the changes in MIP and secondary measures after 8 weeks of IMT. Results: Study recruitment began in August 2021 and, with several disruptions owing to COVID-19, is expected to be completed by December 2023. Conclusions: 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 for improving respiratory muscle function and patient-reported outcomes in individuals with hEDS or G-HSD. Trial Registration: ClinicalTrials.gov NCT04972565; https://clinicaltrials.gov/ct2/show/NCT04972565 International Registered Report Identifier (IRRID): DERR1-10.2196/44832 ",
issn="1929-0748",
doi="10.2196/44832",
url="https://www.researchprotocols.org/2023/1/e44832",
url="https://doi.org/10.2196/44832",
url="http://www.ncbi.nlm.nih.gov/pubmed/36939815"
}