Diaphragmatic Function as a Biomarker

Recruiting

• Conditions: Fibrosis; Dyspnea; Asthmatic; Pulmonary Hypertension; Dyspnea; COPD; Asthma

• Registration Number: NCT05903001
• Lead Sponsor: RWTH Aachen University

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.

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 Timeline

• Study First Submitted: 2023-05-18
• Study First Submitted QC: 2023-06-05
• Study First Posted: 2023-06-15
• Study Start: 2023-07-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-21
• Last Update Posted: 2023-11-22
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 800

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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 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.
Blood Gas Analysis in cmH2O	6 months recruiting	carbon dioxide partial pressure (pCO2)
6 minute walking distance in m	6 months recruiting	Measurement of achieved walking distance in 6 minutes
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.
Diaphragm thickness at functional capacity (FRC)	6 months recruiting	Via ultrasound, the diaphragm thickness at FRC is measured after a normal expiration.
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.
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.
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	6 months recruiting	pH scale
Blood Gas Analysis in mmol/l	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).
Blood Gas Analysis in (I1/s) percent	6 months recruiting	Base Excess
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.
Body Plethysmography	6 months recruiting	TLC (Total lung capacity) in percent predicted.

Trial Locations

Locations (1)

RWTH Aachen University Hospital; 🇩🇪 Aachen, North Rhine-westphalia, Germany