Effects of Adding Yoga Respiratory Training to Osteopathic Manipulative Treatment in Pulmonary Arterial Hypertension

Study Overview
=================
Brief Summary
-----------------
The investigators planned a randomized controlled study to investigate the effects of adding yoga respiratory training to osteopathic manipulative treatment (OMT), and OMT alone on exhaled nitric oxide level and cardiopulmonary function in patients with pulmonary arterial hypertension (PAH). Our hypothesis is that combined intervention including OMT and yoga respiratory training may improve exhaled nitric oxide level and cardiopulmonary function in patients with PAH.

Detailed Description
-----------------
Pulmonary arterial hypertension (PAH) is characterized by a mean pulmonary arterial pressure of >20 mmHg, measured by right heart catheterization at rest. PAH begins in the small arteries of the pulmonary vasculature and is characterized by increased vasoconstriction. Pulmonary vasodilatation induced by perivascular nerve stimulation usually occurs with nitric oxide (NO). A decrease in the airway wall concentration of NO was detected in patients with PAH. It has been reported that patients with PAH have a mild to moderate decrease in lung volumes associated with disease severity. A decrease in exercise capacity and respiratory muscle strength has been reported in patients with PAH. Osteopathic Manipulative Therapy (OMT) is a well-known manual therapy approved by World Health Organization. A single-session of OMT was found to increase pulmonary function, inspiratory muscle strength, oxygen saturation, and to reduce dyspnea and fatigue in individuals with severe chronic obstructive pulmonary disease. It has been observed that OMT increases parasympathetic activity and reduces blood pressure in patients with hypertension. Pranayama breathing is an important component of of yoga. It has been reported that yoga respiratory training increases vagal tone and reduces sympathetic activity, increases vital capacity, controls heart rate and blood pressure, and improves respiratory muscle strength. No study investigating the effects of adding yoga respiratory training to osteopathic manipulative treatment in patients with PAH was found in the literature. The investigators aimed to explore the effects of a combined intervention consisting of OMT and yoga breathing exercises, as well as OMT alone on exhaled NO level, pulmonary function, respiratory and peripheral muscle strength, and exercise capacity in patients with PAH.

Official Title
-----------------
Effects of Adding Yoga Respiratory Training to Osteopathic Manipulative Treatment on Exhaled Nitric Oxide Level and Cardiopulmonary Function in Patients With Pulmonary Arterial Hypertension

Conditions
-----------------
Pulmonary Arterial Hypertension

Intervention / Treatment
-----------------
* Other: Osteopathic manipulative treatment
* Other: Yoga respiratory training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pulmonary hypertension patients that are clinically and hemodynamically stable Resting mean pulmonary arterial pressure > 20 millimeter of mercury (mmHg) during a right heart catheterization Being over 18 years old Volunteering to participate in the study and to sign a written informed consent form Patients with New York Heart Association (NYHA) functional class I-II-III Stable pulmonary hypertension patients that takes medication at least 3 months. Exclusion Criteria: Acute decompensated heart failure Unstable angina pectoris Recent thoracic or abdominal surgical procedures Severe neurological impairments Severe cognitive impairment Recent syncope Using the immune system drugs as a result of organ or tissue transplants Fractures within the past six months Osteoporosis Tumors Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined intervention<br>Combined intervention group consisted of 16 pulmonary arterial hypertension (PAH) patients. Three different yoga breathing exercises were applied after osteopathic manipulative treatment (OMT). This combined intervention was applied 2 times a week for a period of 8 weeks with a total of 16 training sessions. There remained a 3-workday gap between two sessions. Patients in this group were thought about pathophysiology of PAH, benefits of physical activity, airway clearance, oxygen therapy, and importance of proper nutrition, adequate sleep, effective breathing after baseline assessment. | Other: Osteopathic manipulative treatment<br>* The investigators applied six different OMT techniques including rib raising, diaphragm release, suboccipital decompression, first rib mobilization, mediastinum mobilization and thoracic inlet myofascial release. Rib raising is used to increase the mobility of the rib cage and to reduce vasoconstriction by regulating sympathetic tone. Diaphragm release is used to increase diaphragm movement. Suboccipital decompression involves traction of the base of the skull. We aim to improve respiration with mobilization of the first rib which is associated with sternum, sympathetic truncus and important vascular structures. Thoracic inlet is an important structure resisting intrathoracic pressure changes during respiration. Finally, the goal of the mediastinum mobilization is to increase the mobility of the rib cage by providing relaxation in the tension of the facial tissues.<br>Other: Yoga respiratory training<br>* Nadishodhana pranayama (Alternate nostril breathing), Ujjayi pranayama (Psychic breath) and Bhramari pranayama (Humming bee breath) were used for the study. Nadishodhana is one of the most common yoga breathing exercises and involves breathing through one nostril while closing the other one. The patients performed 2 sets of 8 breathing cycles with a resting time of 2 minutes between the sets. Ujjayi Pranayama involves soft contraction of laryngeal muscles and the partial closure of the glottis. The patients performed 2 sets of 10 breathing cycles per session with an inspiration:expiration phase as 1:2. Bhramari Pranayama includes a nasal humming sound during exhalation to create slight vibrations on the laryngeal walls, and the inner walls of the nostrils. The patients applied 2 sets of 10 breathing cycles per session with a respiration rate of 3-4/min.<br>|
| Active Comparator: Osteopathic manipulative treatment<br>OMT group consisted of 16 PAH patients. Six different OMT techniques were applied 2 times a week for a period of 8 weeks with a total of 16 sessions. The same osteopathic manipulative treatment techniques applied to combined intervention group were used for this study group. There remained a 3-workday gap between two sessions. Patients in this group were thought about pathophysiology of PAH, benefits of physical activity, airway clearance, oxygen therapy, and importance of proper nutrition, adequate sleep, effective breathing after baseline assessment. | Other: Osteopathic manipulative treatment<br>* The investigators applied six different OMT techniques including rib raising, diaphragm release, suboccipital decompression, first rib mobilization, mediastinum mobilization and thoracic inlet myofascial release. Rib raising is used to increase the mobility of the rib cage and to reduce vasoconstriction by regulating sympathetic tone. Diaphragm release is used to increase diaphragm movement. Suboccipital decompression involves traction of the base of the skull. We aim to improve respiration with mobilization of the first rib which is associated with sternum, sympathetic truncus and important vascular structures. Thoracic inlet is an important structure resisting intrathoracic pressure changes during respiration. Finally, the goal of the mediastinum mobilization is to increase the mobility of the rib cage by providing relaxation in the tension of the facial tissues.<br>|
| No Intervention: Control<br>Control group also consisted of 16 PAH patients and serves as the controls. No interventions were applied for the patients in this group. Similar with the patients in other two groups, pharmacological treatment of the patients in this group continued and they were advised for using their medication properly, Patients in this group were also thought about pathophysiology of PAH, benefits of physical activity, airway clearance, oxygen therapy, and importance of proper nutrition, adequate sleep, effective breathing after baseline assessment. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Forced Vital Capacity (FVC), Forced Expiratory Volume in One Second (FEV1) at 8 weeks | FVC and FEV1 were recorded in liter (l) by using spirometry (Spiro USB, CareFusion US). Measurements were performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations. | Baseline and week 8 | 
| Change from Baseline Forced Expiratory Volume in One Second/Forced Vital Capacity (FEV1/FVC) at 8 weeks | FEV1/FVC ratio (%) was recorded with regards to the highest FEV1 and FVC values measured by spirometry. | Baseline and week 8 | 
| Change from Baseline Forced Expiratory Flow at 25-75% of FVC (FEF25-75) at 8 weeks | FEF25-75 was recorded in liter/second (l/s) by using spirometry (Spiro USB, CareFusion US). Measurements were performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations. | Baseline and week 8 | 
| Change from Baseline Peak Expiratory Flow (PEF) at 8 weeks | PEF was recorded in liter/minute (l/min) by using spirometry (Spiro USB, CareFusion US). Measurements were performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) recommendations. | Baseline and week 8 | 
| Change from Baseline FVC%, FEV1%, FEF25-75%, PEF% at 8 weeks | FVC%, FEV1%, FEF25-75% and PEF% were recorded as the percentage of predicted values. | Baseline and week 8 | 
| Change from Baseline Nitric Oxide Level at 8 weeks | Fractional Exhaled Nitric Oxide (FeNO) was measured according to ATS/ERS recommendations with a hand-held, portable device (NObreath, Bedfont, UK). After inhaling the ambient air for 2-3 seconds until the total lung capacity, the patient is asked to exhale into the device for more than 6 seconds at constant flow rate (50 milliliter/second) without holding breath. The mean of two technically acceptable values within 10% was recorded in parts per billion (ppb) and maximum six attempts were performed. | Baseline and week 8 | 
| Change from Baseline Exercise Capacity at 8 weeks | Exercise capacity was measured with the 6 Minute Walk Test (6MWT) according to the ATS guidelines. The 6 minutes wallking distance (6MWD) was recorded in meters. Higher scores indicate a better outcome. | Baseline and week 8 | 
| Change from Baseline 6MWD% at 8 weeks | 6MWD% was recorded as the percentage of predicted distances. Higher scores indicate a better outcome. | Baseline and week 8 | 
| Change from Baseline Changes of Perceived Dyspnea and Fatigue at 8 weeks | Perceived dyspnea and fatigue were measured before and immediately after 6MWT with modified Borg scale ranging from 0 to 10. Higher scores indicate a worse outcome. Changes of perceived dyspnea and fatigue were recorded. | Baseline and week 8 | 
| Change from Baseline Resting Peripheral Oxygen Saturation (SpO2) at 8 weeks | SpO2 was measured by using a pulse oximeter and was recorded as percentage. | Baseline and week 8 | 
| Change from Baseline Change of Blood Pressure at 8 weeks | Systolic and diastolic blood pressures were measured before and immediately after 6MWT with sphygmomanometer. Change of systolic blood pressure and change of diastolic blood pressure were recorded. | Baseline and week 8 | 
| Change from Baseline Resting Heart Rate at 8 weeks | Resting heart rate was measured with a pulse oximeter and was recorded as beats per minute (bpm). | Baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Respiratory Muscle Strength at 8 weeks | MIP and MEP were recorded as cmH2O, as well as MIP% and MEP% were recorded as the percentage of predicted values according to age and gender, as described by Black and Hyatt. | Baseline and week 8 | 
| Change from Baseline Peripheral Muscle Strength at 8 weeks | Hand grip strength was measured with a hand-held dynamometer bilaterally. Three measurements on both hands were performed and the highest values were recorded in kilograms. | Baseline and week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pulmonary arterial hypertension, Yoga respiratory training, Osteopathic manipulative treatment, Exhaled nitric oxide, Cardiopulmonary function