Individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) often experience dyspnea. Inspiratory Muscle Training (IMT) has been shown to improve dyspnea and respiratory muscle function; however, the impact of IMT in combination with whole-body exercise training on respiratory muscle strength, dyspnea, and daily function remains unknown. The objectives of this research are i) to evaluate dyspnea, respiratory muscle strength and function, ventilatory parameters, and health-related quality of life (HRQL) in individuals with hEDS and HSD compared to healthy age and sex-matched controls, ii) to explore the contributors to dyspnea during exercise with a specific focus on respiratory muscle structure and function in hEDS and HSD patients and healthy controls, and iii) to assess whether the combination of IMT and whole-body exercise training will be more effective than whole-body exercise training alone in improving participant outcomes in hEDS and HSD participants. It is hypothesized that i) hEDS and HSD participants will have lower respiratory muscle strength, higher peripheral airway resistance, lower HRQL, and higher anxiety and depression levels compared to healthy controls, ii) the contributors to increased exercise induced dyspnea will include decreased respiratory muscle strength, increased airway resistance, and greater prefrontal cortical neural activity, and iii) the combination of IMT and whole-body exercise training will be superior to whole-body training alone for improving dyspnea, respiratory muscle strength and endurance, aerobic capacity, HRQL, anxiety, and depression.
Thirty-four hEDS and HSD participants will be recruited from the University Health Network (Toronto, Canada). Participants will have baseline evaluations of dyspnea, pulmonary function tests (i.e., oscillometry, spirometry, and lung volumes), respiratory muscle structure and function (i.e., diaphragm ultrasound and respiratory muscle strength), HRQL, anxiety and depression. Symptom limited cardiopulmonary exercise testing will be utilized to quantify exertional dyspnea using the 10-item Borg dyspnea scale, 18-point qualitative dyspnea assessment scale, peak oxygen uptake (peak VO2), and assessment of dynamic ventilatory parameters. Neural activity in the pre-frontal cortex will be measured during cardiopulmonary exercise testing via functional near-infrared spectroscopy. These baseline measures will be compared to 17 age and sex-matched healthy controls. After baseline assessments, hEDS and HSD participants will be randomized to one of the following groups: i) Usual Care plus IMT: 8 weeks of whole-body exercises (standard care provided to hEDS and HSD patients at the University Health Network) plus a concurrent IMT intervention 5 times per week); ii) Usual Care: 8 weeks of whole-body exercises (as outlined above). After four and eight weeks, participants will have repeat assessments as described below. Exertional dyspnea is a prevalent and troublesome symptom experienced by individuals living with hEDS and HSD. This study will provide a better understanding of the underlying contributors of dyspnea in hEDS and HSD patients, with a focus on respiratory muscle structure and function, prefrontal cortical neural activity, and ventilatory parameters, both at rest and with exertion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Participants will receive usual care and will also be provided with a personalized prescription for an IMT program for 8 weeks. Participants will perform two daily IMT sessions of 30 breaths (\< 5 minutes/session), 5 days per week in their home environment. IMT intensity will be progressed weekly by 5-10% of the baseline maximal inspiratory pressure if the Borg Dyspnea score is \< 7.
University Health Network
Toronto, Ontario, Canada
Maximal Inspiratory Pressure
Maximal inspiratory pressure will be evaluated using standard methods in the pulmonary function laboratory, with the highest value (cm H2O) taken within 10 percent of the other readings as per American Thoracic Society recommendations.
Time frame: Change from baseline at 8 weeks
Maximal Expiratory Pressure
Maximal expiratory pressure will be evaluated using standard methods in the pulmonary function laboratory, with the highest value (cm H2O) taken within 10 percent of the other readings as per American Thoracic Society recommendations.
Time frame: Change from baseline at 8 weeks
Respiratory Muscle Endurance
Respiratory muscle endurance (endurance time measured in seconds) will be assessed using a manual threshold loading device (Philips Threshold trainer).
Time frame: Change from baseline at 4 weeks and 8 weeks
Inspiratory Muscle Training Workload
Total IMT workload per session (product of inspiratory muscle force and inhaled volume expressed in Joules) will be extracted from the IMT device in the experimental group.
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Load
Inspiratory muscle training Load (cm H2O) will be abstracted from the IMT device in the experimental group.
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Power
Inspiratory muscle training mean power per breath (Watts) will be abstracted from the IMT device in the experimental group.
Time frame: Through study completion, an average of 8 weeks
Inspiratory Muscle Training Mean Volume
Inspiratory muscle training mean volume per breath (Litres) will be abstracted from the IMT device in the experimental group.
Time frame: Through study completion, an average of 8 weeks
Medical Research Council Dyspnea Scale
The Medical Research Council Dyspnea Scale will be used to assess the effect of breathlessness on daily activities. The scale comprises five statements that describe the range of respiratory dyspnea from none (Grade 1) to severe with difficulties performing self-care (Grade 5).
Time frame: Change from baseline at 8 weeks
Borg Dyspnea Scale
The 10-point Borg Dyspnea Scale will be used throughout the study to adjust the intensity of inspiratory muscle training sessions The lowest score (0) corresponds to the sensation of normal breathing (absence of dyspnea) and the highest score (10) corresponds to the maximum possible sensation of dyspnea.
Time frame: Through study completion, an average of 8 weeks
Borg Dyspnea Scale
The 10-point Borg Dyspnea Scale will be used during cardiopulmonary exercise testing to characterize degree of dyspnea. The lowest score (0) corresponds to the sensation of normal breathing (absence of dyspnea) and the highest score (10) corresponds to the maximum possible sensation of dyspnea.
Time frame: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
The 18-point Qualitative Dyspnea Scale will be ascertained at the end of cardiopulmonary exercise testing. Participants will be presented with a list of 18 descriptors characterizing their dyspnea and will be asked to rank the top three.
Time frame: Change from baseline at 8 weeks
Qualitative Assessment of Dyspnea
The 18-point Qualitative Dyspnea Scale will be ascertained at the end of respiratory muscle endurance testing. Participants will be presented with a list of 18 descriptors characterizing their dyspnea and will be asked to rank the top three.
Time frame: Change from baseline at 4 weeks and 8 weeks
Oscillometry
Oscillometry will be performed in the pulmonary function laboratory following the protocol from the European Respiratory Society.
Time frame: Change from baseline at 8 weeks
Spirometry (Forced Vital Capacity)
Spirometry (forced vital capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Time frame: Change from baseline at 8 weeks
Spirometry (Forced Expiratory Volume in 1 Second)
Spirometry (forced expiratory volume in 1 second) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Time frame: Change from baseline at 8 weeks
Lung Volumes (Total Lung Capacity)
Lung volumes (i.e., Total Lung Capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Time frame: Change from baseline at 8 weeks
Lung Volumes (Inspiratory Capacity)
Lung volumes (i.e., inspiratory capacity) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Time frame: Change from baseline at 8 weeks
Lung Volumes (Residual Volume)
Lung volumes (i.e., Residual Volume) will be measured in the pulmonary function laboratory following the American Thoracic Society Guidelines.
Time frame: Change from baseline at 8 weeks
Diaphragm Thickness
The right hemi-diaphragm thickness will be measured using a 13 megahertz ultrasound transducer.
Time frame: Change from baseline at 8 weeks
Diaphragm Thickening Fraction
The right hemi-diaphragm thickening fraction will be measured using a 13 megahertz ultrasound transducer.
Time frame: Change from baseline at 8 weeks
Peak Oxygen Uptake During Cardiopulmonary Exercise Testing
Cardiopulmonary exercise test-based assessment of peak oxygen uptake (VO2 peak) will be performed on a cycle ergometer.
Time frame: Change from baseline at 8 weeks
Ventilatory Response During Cardiopulmonary Exercise Testing
Ventilatory response will be assessed during cardiopulmonary exercise testing (on a cycle ergometer) with exhaled gas measurements captured breath by breath.
Time frame: Change from baseline at 8 weeks
Heart Rate Response During Cardiopulmonary Exercise Testing
Heart rate response will be assessed during cardiopulmonary exercise testing on a cycle ergometer.
Time frame: Change from baseline at 8 weeks
Pre-frontal Cortical Neural Activity During Cardiopulmonary Exercise Testing
Oxygenated and total hemoglobin of the prefrontal cortex will be measured with Functional Near Infrared Spectroscopy during cardiopulmonary exercise testing.
Time frame: Change from baseline at 8 weeks
Physical Activity Levels
Physical activity (daily steps) will be measured via a tracking device (Fitbit, San Francisco, USA) for a 7-day period.
Time frame: Change from baseline at 4 weeks and 8 weeks
Leisure-Time Exercise
Leisure-time exercise will be measured via the 3-item Godin Leisure-Time Exercise Questionnaire - Leisure Score Index. The Leisure Score Index is used to rank individuals from the lowest to highest exercise levels: sedentary (score less than 14 units); moderately active (score of 14-23 units); and active (24 units or more).
Time frame: Baseline
Health-Related Quality of Life
The Short-Form 36 Health Survey (SF-36) will be used to assess general health-related quality of life. The SF-36 consists of eight scaled scores (total score ranging from 0 to 100), with lower scores representing lower health-related quality of life.
Time frame: Change from baseline at 8 weeks
Depression, Anxiety and Stress Scale
The Depression, Anxiety and Stress Scale (DASS-21) questionnaire has 21 items to assess mood (anxiety, depression, and stress). Each statement for the three domains is given a score of 0 (not applicable) to 3 (applicable most of the time) with scores categorized as follows: Normal, Mild, Moderate, Severe, and Extremely Severe.
Time frame: Change from baseline at 8 weeks
Participant Study Recruitment
Recruitment-success percentage and reasons for participation/non-participation in the study will be collected.
Time frame: Over the study period (8 weeks)
Participant Retention in the Study
Participant retention will be assessed by measuring participant follow-up with testing throughout the study period.
Time frame: Over the study period (8 weeks)
Adherence to Inspiratory Muscle Training Load
Adherence to the IMT intervention will be tracked electronically via the IMT device (i.e., percentage of the maximal inspiratory pressure prescribed).
Time frame: Over the intervention period (8 weeks)
Adherence to Inspiratory Muscle Training Days
Adherence to the IMT intervention will be tracked using a participant log to record the number of training days completed each week.
Time frame: Over the intervention period (8 weeks)
Adverse Events During Inspiratory Muscle Training Practice (Safety and Tolerability)
Any adverse events (i.e. prolonged muscle soreness, pneumothorax) with IMT will be assessed throughout the study period.
Time frame: Over the intervention period (8 weeks)
Participant Satisfaction with the IMT Intervention
A multiple-choice and free-form questionnaire assessing the participants' satisfaction with the IMT intervention will be completed by study participants.
Time frame: Change from baseline at weeks 1, 4 and 8
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.