DFUNBIO: Diaphragmatic Function as a Biomarker

Sponsor

RWTH Aachen University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05903001

Collaborator

(none)

800

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Dyspnea; Asthmatic COPD Fibrosis Pulmonary Hypertension Asthma Dyspnea	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

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

800 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Diaphragmatic Function as a Biomarker in Patients With Respiratory Diseases

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Dyspnea Borg scale 1 to 10 [6 months recruiting]
Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Dyspnea Borg scale 1 to 10 [follow up 3 months after recruitment]
Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Dyspnea Borg scale 1 to 10 [follow up 6 months after recruitment]
Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Dyspnea Borg scale 1 to 10 [follow up 12 months after recruitment]
Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Dyspnea Borg scale 1 to 10 [follow up 18 months after recruitment]
Borg scale before and after "6 minute walking distance" test. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.

Secondary Outcome Measures

6 minute walking distance in m [6 months recruiting]
Measurement of achieved walking distance in 6 minutes
Sit-to stand-test (60 seconds) [6 months recruiting]
Measurement of achieved repetitions of standing up and sitting down from an initial seated position in 60 seconds.
New York Heart Association (NYHA) classification scale 1 to 4 [6 months recruiting, follow up up to 18 months after last recruitment]
Patients are linked to a NYHA degree. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Modified Medical Research Council (MRC) Breathlessness Scale 1 to 5 [6 months recruiting, follow up up to 18 months after last recruitment]
Patients are assessed and grouped according to their MRC Breathlessness Scale. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Chronic Respiratory Questionnaire (CRQ) [6 months recruiting, follow up up to 18 months after last recruitment]
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.
COPD Assessment Test (CAT-Questionnaire) from 0 to 40 points. [6 months recruiting, follow up up to 18 months after last recruitment]
Patients are evaluated and placed into the corresponding groups. Lower scores show fewer dyspnea, higher scores indicate more dyspnea.
Global Initiative for Asthma (GINA) classification [6 months recruiting, follow up up to 18 months after last recruitment]
Patients are assessed and grouped as mild, moderate, or severe according to the GINA classification.
Body Plethysmography [6 months recruiting]
TLC (Total lung capacity) in percent predicted.
Diaphragm Thickening Ratio (DTR) in percent [6 months recruiting]
Via ultrasound, the diaphragm thickening ratio (DTR) was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC).
Diaphragm thickness at Total lung capacity (TLC) [6 months recruiting]
Via ultrasound, the diaphragm thickness at TLC is measured at the maximum point of inspiration.
Diaphragm thickness at functional capacity (FRC) [6 months recruiting]
Via ultrasound, the diaphragm thickness at FRC is measured after a normal expiration.
Diaphragm ultrasound sniff velocity in cm/s [6 months recruiting]
Via ultrasound, the diaphragm sniff velocity was assessed during tidal breathing and following a maximum sniff.
Intercostal Muscle ultrasound thickness at Total lung capacity (TLC) in cm [6 months recruiting]
Via ultrasound, the intercostal thickness at TLC is measured at the maximum point of inspiration.
Intercostal Muscle ultrasound thickness at functional capacity (FRC) in cm [6 months recruiting]
Via ultrasound, the intercostal thickness at FRC is measured after a normal expiration.
Intercostal Muscle Thickening Ratio in percent [6 months recruiting]
Via ultrasound, the intercostal muscle thickening ratio was calculated as thickness at total lung capacity (TLC) divided by thickness at functional residual capacity (FRC).
Maximum Inspiratory Pressure (MIP) in percent predicted [6 months recruiting]
Measurement of Maximum Inspiratory Pressure
Maximum Expiratory Pressure (MEP) in percent predicted [6 months recruiting]
Measurement of Maximum Expiratory Pressure
Sniff Nasal Inspiratory Pressure (SNIP) in percent predicted [6 months recruiting]
Measurement of Sniff Nasal Inspiratory Pressure
Blood Gas Analysis in cmH2O [6 months recruiting]
oxygen partial pressure (pO2)
Blood Gas Analysis in cmH2O [6 months recruiting]
carbon dioxide partial pressure (pCO2)
Blood Gas Analysis [6 months recruiting]
pH scale
Blood Gas Analysis in mmol/l [6 months recruiting]
Base Excess
Blood Gas Analysis in (I1/s) percent [6 months recruiting]
Base Excess
Electromyography (EMG) [6 months recruiting]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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