Effects of Mud Bath Therapy in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Rehabilitation and physical therapy strategies targeting extra pulmonary manifestations of Chronic Obstructive Pulmonary Disease (COPD)are far from being well defined. Studies, performed in healthy subjects using threshold breathing device [a simple method to increase inspiratory muscle load] have shown that ventilatory muscle overactivation during loaded breathing may prime reactive oxygen species (ROS) production, thus initiating an inflammatory response that results in elevation of pro-inflammatory cytokines, particularly IL_6. Increase of cytokine IL_6 in turn, elicits a cascade of systemic responses, involving hormone like glucoregulatory mechanisms, lipolysis and fat oxidation, as well as control of breathing. Thermal mud bath therapy has been acknowledged for its antioxidant and anti-inflammatory effects in several chronic diseases. However, it is not considered among treatment options of chronic pulmonary disease. Previous experimental studies indicate that trace elements of thermal treatments, particularly iodide and bromide, may positively intervene in the setup and maintenance of active state in skeletal muscle. These findings suggest that in COPD patients these elements may improve the loading and endurance of respiratory muscles and therefore blunt ventilatory muscle overactivation and the ensuing inflammatory cytokine response. In this study the investigators want to test two major hypotheses. First, that mud bath therapy reduces systemic inflammatory processes in COPD patients, increases respiratory muscle endurance and normalizes the ventilatory response. Second, that the increase in systemic inflammation after IRB exercise is blunted by mud bath therapy.

Detailed Description
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The impact of extra pulmonary manifestations of Chronic Obstructive Pulmonary Disease (COPD) on physical performance and quality of life, together with the notion that plasma cytokines in COPD is not due to an overflow of inflammatory mediators from the lung compartment, raise interest in understanding the potential link between lung and systemic inflammation. Recent studies, performed in normal subjects using threshold breathing device [a simple method to increase respiratory resistance and inspiratory muscle load] have shown that ventilatory muscle activation during loaded breathing may prime reactive oxygen species (ROS) production, thus initiating an inflammatory response within diaphragm that results in systemic elevation of pro-inflammatory cytokines. These findings provide a sound working hypothesis about the origin of systemic inflammation in COPD. Endurance and task failure of inspiratory muscles can be challenged during inspiratory resistive breathing (IRB) exercise performed with either nonlinear or threshold loading devices [4-6], thus allowing to simulate resistive breathing caused by airway narrowing occurring during COPD exacerbations Therapy with mineral water is a widely used modality of physical therapy in countries rich in mineral water. Up to date, however, it is not considered among treatment options of chronic pulmonary disease by recent guidelines. Mud bath therapy has been acknowledged for its antioxidant and anti-inflammatory effects in several chronic diseases. Although full mechanisms of such effects have not yet been fully elucidated, previous in vivo studies on the effects of several anions on the duration of active state in skeletal muscle indicate that trace elements of thermal treatments, particularly iodide and bromide, may positively intervene in the setup and maintenance of this active state. These findings suggest that in COPD patients these elements may improve the loading and endurance of respiratory muscles and therefore blunt ventilatory muscle overactivation and the ensuing inflammatory cytokine response. In this study the investigators want to test two major hypotheses. First, that mud bath therapy reduces systemic inflammatory processes in COPD patients, increases respiratory muscle endurance and normalizes the ventilatory response. Second, that the increase in systemic inflammation after IRB exercise is blunted by mud bath therapy.

Official Title
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Effects of Mud Bath Therapy in Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Other: Mud bath Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >/= 45 years 34% </= FEV1 </= 70% stable clinical conditions Exclusion Criteria: idiopathic or acquired bronchiectasis cardiovascular, peripheral vascular or cerebrovascular disease systemic confounding inflammatory disease (e.g rheumatoid arthritis,Crohn's disease, systemic vasculitis etc.) malignancies

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mud Bath therapy<br> | Other: Mud bath Therapy<br>* patients will be randomized to Mud bath Therapy ( 12 sessions) or no treatment<br>* Other names: Thermal treatment;|
| No Intervention: no Mud Bath Therapy<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in cytokine IL6 at 2weeks +2days (after Mud Bath Therapy) | Subjects for the study will be 42 mild-to-severe COPD outpatients. They will carry out baseline venous and arterial capillary blood sampling, ventilatory response tests and assessment of pulmonary function, before and after loaded breathing (IRB)test. Patients will then be randomized to standard mud bath therapy (12 sessions) or no-treatment. All tests and measurements will be repeated afterwards. | baseline test before IRB, at Day 17 | 
| Change before-after IRB test in cytokine IL_6, at baseline | Subjects for the study will be 42 mild-to-severe COPD outpatients. They will carry out baseline venous blood sampling, before and after loaded breathing (IRB)test. Change before-after IRB test in IL_6 will be assessed at baseline(day 0). | before-after IRB test, at Day 0 | 
| Change before-after IRB test in cytokine IL_6, at 2 weeks +2 days | Subjects for the study will be 42 mild-to-severe COPD outpatients. They will carry out baseline venous blood sampling, before and after loaded breathing (IRB) test. Change before-after IRB test in IL_6 will be assessed again at 2 weeks + 2days(day 17, after Mud Bath Therapy). | before-after IRB test, at Day 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in respiratory muscle endurance time, at 2weeks +2days | Time duration of sustainable inspiratory pressure, set at 50% of MIP | IRB test duration, at Day 17 | 
| Change from baseline in Ventilatory Response to CO2, at 2weeks +2days | Ventilatory response to CO2 (VRCO2), is conducted according to Read's technique. The subjects will be seated comfortably, attached to the mouthpiece with a noseclip in place and breathing room air until the end-tidal PCO2 (Pet,CO2) stabilized. They then will start rebreathing a mixture of approximately 7% CO2 and 93% O2. Rebreathing was continued for at least 3 minutes. | Baseline test at day 17 | 
| Change before-after IRB test in VRCO2, at day 0 | Ventilatory response to CO2 (VRCO2), conducted according to Read's technique, will be obtained before and after IRB test, at day 0 | before-after IRB test, at Day 0 | 
| Change before-after IRB test in VRCO2, at day 17 | Ventilatory response to CO2 (VRCO2), conducted according to Read's technique, will be obtained before and after IRB test, at day 17 | before-after IRB test, at Day 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Intensive Resistive Breathing, Cytokine IL6,