Diaphragmatic Function as a Biomarker

Study Overview
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Brief Summary
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Dyspnea is among the most common symptoms in patients with respiratory diseases such as Asthma, chronic obstructive pulmonary disease (COPD), Fibrosis, and Pulmonary Hypertension. However, the pathophysiology and underlying mechanisms of dyspnea in patients with respiratory diseases are still poorly understood. Diaphragm dysfunction might be highly prevalent in patients with dyspnea and respiratory diseases. The association of diaphragm function and potential prognostic significance in patients with respiratory diseases has not yet been investigated.

Detailed Description
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The aim of the present project is to comprehensively measure respiratory muscle function and strength in patients with respiratory diseases. The investigators attempt to recruit 800 patients across four disease groups (Asthma, COPD, Fibrosis, and Pulmonary Hypertension) and the investigators intend to measure diaphragm and accessory respiratory muscle function and strength, lung function, and exercise tolerance, as well as the participants' symptom burden during one day at baseline in the investigators' lab. Thereafter, the investigators will follow up on patients by phone 3 months, 6 months, 12 months and 18 months after the investigators have seen them in the investigators' lab. Based on these results, not only the association between dyspnea exercise tolerance and diaphragm function in patients with respiratory diseases can be assessed, but also the prognostic significance of diaphragm dysfunction in these patients can be determined. As such, hospitalization and exacerbation requiring the intake of steroids will be assessed and followed up on by phone, and therefore the prognostic significance of diaphragm dysfunction in predicting hospitalization and the intake of steroids can be determined.

Official Title
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Diaphragmatic Function as a Biomarker in Patients With Respiratory Diseases

Conditions
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Dyspnea, COPD, Asthma, Dyspnea; Asthmatic, Fibrosis, Pulmonary Hypertension

Intervention / Treatment
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* Diagnostic Test: Diaphragm Ultrasound
* Diagnostic Test: Intercostal Muscle Ultrasound
* Diagnostic Test: Borg scale
* Diagnostic Test: MRC Breathlessness Scale
* Diagnostic Test: Respiratory Questionaire
* Diagnostic Test: GINA classification of Asthma
* Diagnostic Test: Measurement of respiratory mouth pressure
* Diagnostic Test: SNIP
* Diagnostic Test: 6-minute walking distance
* Diagnostic Test: 60 seconds sit-to-stand test
* Diagnostic Test: Electromyography
* Diagnostic Test: Lung Function
* Diagnostic Test: CAT-Questionnaire
* Diagnostic Test: European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient has one of the following lung diseases: COPD, bronchial asthma, pulmonary fibrosis, pulmonary hypertension is 18 years or older is mentally and physically able to understand the study and to follow instructions are legally competent signed declaration of consent Exclusion Criteria: BMI > 35 current or treatments or diseases in the past which could influence the evaluation of the study Expected lack of willingness to actively participate in study-related measures alcohol or drug abuse disc herniation/prolapse epilepsy wheelchair bound in custody due to an official or court order in a dependent relationship or employment relationship with investigating physician or one of their deputy emergency inpatient hospital stay within 4 weeks before study-specific examinations

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Asthma<br> | Diagnostic Test: Diaphragm Ultrasound<br>* Ultrasound of the Diaphragm at the end of inspiration and expiration<br>Diagnostic Test: Intercostal Muscle Ultrasound<br>* Ultrasound of the Intercostal Muscles at the end of inspiration and expiration<br>Diagnostic Test: Borg scale<br>* Questionnaire for Perceived Exertion (Borg Rating of Perceived Exertion Scale)<br>Diagnostic Test: MRC Breathlessness Scale<br>* The MRC Dyspnoea Scale allows the patients to indicate the extent to which their breathlessness affects their mobility.<br>Diagnostic Test: Respiratory Questionaire<br>* Specialized respiratory questionnaire with different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain)<br>Diagnostic Test: GINA classification of Asthma<br>* Patients are classified according to the GINA classification of Asthma.<br>Diagnostic Test: Measurement of respiratory mouth pressure<br>* Inspiratory and expiratory Measurement of respiratory mouth pressure<br>Diagnostic Test: SNIP<br>* Measurement of Sniff Nasal Inspiratory Pressure<br>Diagnostic Test: 6-minute walking distance<br>* The maximum walking distance achieved in 6 minutes<br>Diagnostic Test: 60 seconds sit-to-stand test<br>* number of repetitions achieved in sitting down and standing up in 60 seconds<br>Diagnostic Test: Electromyography<br>* electromyography of the muscles of respiration via superficial electrodes<br>Diagnostic Test: Lung Function<br>* Measurement of lung function via body plethysmography<br>|
| Patients with COPD<br> | Diagnostic Test: Diaphragm Ultrasound<br>* Ultrasound of the Diaphragm at the end of inspiration and expiration<br>Diagnostic Test: Intercostal Muscle Ultrasound<br>* Ultrasound of the Intercostal Muscles at the end of inspiration and expiration<br>Diagnostic Test: Borg scale<br>* Questionnaire for Perceived Exertion (Borg Rating of Perceived Exertion Scale)<br>Diagnostic Test: MRC Breathlessness Scale<br>* The MRC Dyspnoea Scale allows the patients to indicate the extent to which their breathlessness affects their mobility.<br>Diagnostic Test: Respiratory Questionaire<br>* Specialized respiratory questionnaire with different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain)<br>Diagnostic Test: Measurement of respiratory mouth pressure<br>* Inspiratory and expiratory Measurement of respiratory mouth pressure<br>Diagnostic Test: SNIP<br>* Measurement of Sniff Nasal Inspiratory Pressure<br>Diagnostic Test: 6-minute walking distance<br>* The maximum walking distance achieved in 6 minutes<br>Diagnostic Test: 60 seconds sit-to-stand test<br>* number of repetitions achieved in sitting down and standing up in 60 seconds<br>Diagnostic Test: Electromyography<br>* electromyography of the muscles of respiration via superficial electrodes<br>Diagnostic Test: Lung Function<br>* Measurement of lung function via body plethysmography<br>Diagnostic Test: CAT-Questionnaire<br>* COPD Assessment Test (CAT)<br>|
| Patients with Fibrosis<br> | Diagnostic Test: Diaphragm Ultrasound<br>* Ultrasound of the Diaphragm at the end of inspiration and expiration<br>Diagnostic Test: Intercostal Muscle Ultrasound<br>* Ultrasound of the Intercostal Muscles at the end of inspiration and expiration<br>Diagnostic Test: Borg scale<br>* Questionnaire for Perceived Exertion (Borg Rating of Perceived Exertion Scale)<br>Diagnostic Test: MRC Breathlessness Scale<br>* The MRC Dyspnoea Scale allows the patients to indicate the extent to which their breathlessness affects their mobility.<br>Diagnostic Test: Respiratory Questionaire<br>* Specialized respiratory questionnaire with different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain)<br>Diagnostic Test: Measurement of respiratory mouth pressure<br>* Inspiratory and expiratory Measurement of respiratory mouth pressure<br>Diagnostic Test: SNIP<br>* Measurement of Sniff Nasal Inspiratory Pressure<br>Diagnostic Test: 6-minute walking distance<br>* The maximum walking distance achieved in 6 minutes<br>Diagnostic Test: 60 seconds sit-to-stand test<br>* number of repetitions achieved in sitting down and standing up in 60 seconds<br>Diagnostic Test: Electromyography<br>* electromyography of the muscles of respiration via superficial electrodes<br>Diagnostic Test: Lung Function<br>* Measurement of lung function via body plethysmography<br>|
| Patients with Pulmonary Hypertension<br> | Diagnostic Test: Diaphragm Ultrasound<br>* Ultrasound of the Diaphragm at the end of inspiration and expiration<br>Diagnostic Test: Intercostal Muscle Ultrasound<br>* Ultrasound of the Intercostal Muscles at the end of inspiration and expiration<br>Diagnostic Test: Borg scale<br>* Questionnaire for Perceived Exertion (Borg Rating of Perceived Exertion Scale)<br>Diagnostic Test: MRC Breathlessness Scale<br>* The MRC Dyspnoea Scale allows the patients to indicate the extent to which their breathlessness affects their mobility.<br>Diagnostic Test: Respiratory Questionaire<br>* Specialized respiratory questionnaire with different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain)<br>Diagnostic Test: Measurement of respiratory mouth pressure<br>* Inspiratory and expiratory Measurement of respiratory mouth pressure<br>Diagnostic Test: SNIP<br>* Measurement of Sniff Nasal Inspiratory Pressure<br>Diagnostic Test: 6-minute walking distance<br>* The maximum walking distance achieved in 6 minutes<br>Diagnostic Test: 60 seconds sit-to-stand test<br>* number of repetitions achieved in sitting down and standing up in 60 seconds<br>Diagnostic Test: Electromyography<br>* electromyography of the muscles of respiration via superficial electrodes<br>Diagnostic Test: Lung Function<br>* Measurement of lung function via body plethysmography<br>Diagnostic Test: European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk group<br>* Patients with pulmonary hypertension are classified according to the ESC/ERS risk group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea Borg scale 1 to 10 | Borg scale before and after 6 minute walking distance test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | 6 months recruiting | 
| Dyspnea Borg scale 1 to 10 | Borg scale before and after 6 minute walking distance test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | follow up 3 months after recruitment | 
| Dyspnea Borg scale 1 to 10 | Borg scale before and after 6 minute walking distance test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | follow up 6 months after recruitment | 
| Dyspnea Borg scale 1 to 10 | Borg scale before and after 6 minute walking distance test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | follow up 12 months after recruitment | 
| Dyspnea Borg scale 1 to 10 | Borg scale before and after 6 minute walking distance test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | follow up 18 months after recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 minute walking distance in m | Measurement of achieved walking distance in 6 minutes | 6 months recruiting | 
| Sit-to stand-test (60 seconds) | Measurement of achieved repetitions of standing up and sitting down from an initial seated position in 60 seconds. | 6 months recruiting | 
| New York Heart Association (NYHA) classification scale 1 to 4 | Patients are linked to a NYHA degree. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | 6 months recruiting, follow up up to 18 months after last recruitment | 
| Modified Medical Research Council (MRC) Breathlessness Scale 1 to 5 | Patients are assessed and grouped according to their MRC Breathlessness Scale. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | 6 months recruiting, follow up up to 18 months after last recruitment | 
| Chronic Respiratory Questionnaire (CRQ) | Assessments of different domains (Emotional Domain, Dyspnea Domain, Mastery Domain, Fatigue Domain) in a standardized questionnaire on a scale from 1 to 7. The scores for each question of each dimension are added together and divided by the number of completed questions in each domain. In general, higher scores mean a worse outcome and lower scores mean a better outcome. For the dyspnea domain for example, a high score means that patients have less dyspnea, and a low score means that patients have more dyspnea. | 6 months recruiting, follow up up to 18 months after last recruitment | 
| COPD Assessment Test (CAT-Questionnaire) from 0 to 40 points. | Patients are evaluated and placed into the corresponding groups. Lower scores show fewer dyspnea, higher scores indicate more dyspnea. | 6 months recruiting, follow up up to 18 months after last recruitment | 
| Global Initiative for Asthma (GINA) classification | Patients are assessed and grouped as mild, moderate, or severe according to the GINA classification. | 6 months recruiting, follow up up to 18 months after last recruitment | 
| Body Plethysmography | TLC (Total lung capacity) in percent predicted. | 6 months recruiting | 
| Diaphragm Thickening Ratio (DTR) in percent | Via ultrasound, the diaphragm thickening ratio (DTR) was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC). | 6 months recruiting | 
| Diaphragm thickness at Total lung capacity (TLC) | Via ultrasound, the diaphragm thickness at TLC is measured at the maximum point of inspiration. | 6 months recruiting | 
| Diaphragm thickness at functional capacity (FRC) | Via ultrasound, the diaphragm thickness at FRC is measured after a normal expiration. | 6 months recruiting | 
| Diaphragm ultrasound sniff velocity in cm/s | Via ultrasound, the diaphragm sniff velocity was assessed during tidal breathing and following a maximum sniff. | 6 months recruiting | 
| Intercostal Muscle ultrasound thickness at Total lung capacity (TLC) in cm | Via ultrasound, the intercostal thickness at TLC is measured at the maximum point of inspiration. | 6 months recruiting | 
| Intercostal Muscle ultrasound thickness at functional capacity (FRC) in cm | Via ultrasound, the intercostal thickness at FRC is measured after a normal expiration. | 6 months recruiting | 
| Intercostal Muscle Thickening Ratio in percent | Via ultrasound, the intercostal muscle thickening ratio was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC). | 6 months recruiting | 
| Maximum Inspiratory Pressure (MIP) in percent predicted | Measurement of Maximum Inspiratory Pressure | 6 months recruiting | 
| Maximum Expiratory Pressure (MEP) in percent predicted | Measurement of Maximum Expiratory Pressure | 6 months recruiting | 
| Sniff Nasal Inspiratory Pressure (SNIP) in percent predicted | Measurement of Sniff Nasal Inspiratory Pressure | 6 months recruiting | 
| Blood Gas Analysis in cmH2O | oxygen partial pressure (pO2) | 6 months recruiting | 
| Blood Gas Analysis in cmH2O | carbon dioxide partial pressure (pCO2) | 6 months recruiting | 
| Blood Gas Analysis | pH scale | 6 months recruiting | 
| Blood Gas Analysis in mmol/l | Base Excess | 6 months recruiting | 
| Blood Gas Analysis in (I1/s) percent | Base Excess | 6 months recruiting | 
| Electromyography (EMG) | Measurement of electrical activity during different breathing maneuvers (Sniff, Cough, Valsalva, Mueller) via superficial electrodes placed on the diaphragm and accessory respiratory muscles (Sternocleidomastoideus muscle, intercostal muscles). | 6 months recruiting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumology, dyspnea, COPD, asthma, fibrosis, pulmonary hypertension