Lung Clearance Index and Lung Allograft Dysfunction

Study Overview
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Brief Summary
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The aim of this project is to evaluate the ability of the lung clearance index (LCI) to detect early chronic lung allograft failure (CLAD) in adult lung transplant recipients over a period of 3 years.

Detailed Description
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This single center study consists of three parts: Characterisation of the Zurich lung transplant cohort regarding CLAD status and pulmonary function impairment (cross-sectional, study part I) Evaluation of test-retest reliability of LCI in 20 clinically stable lung transplant recipients during three consecutive study visits (study part II) Prospective cohort study to test the ability of LCI to detect early CLAD in patients without prior CLAD (study part III)

Official Title
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Lung Clearance Index for the Early Detection and Monitoring of Lung Allograft Dysfunction After Adult Lung Transplantation

Conditions
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Lung Transplantation, Chronic Lung Allograft Dysfunction, Rejection Lung Transplant

Intervention / Treatment
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* Other: Early detection of CLAD by Lung Clearance Index (LCI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female lung transplant recipients Written informed consent by the participant after information about the research project Exclusion Criteria: Any contraindication to perform pulmonary function tests (e.g., persistent pneumothorax) Acute airway infection Chronic infection due to Burkholderia spp and nontuberculosis mykobacteria NTM

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

| Intervention/Treatment |
| --- |
|Other: Early detection of CLAD by Lung Clearance Index (LCI)|Lung transplant candidates without prior CLAD (evaluated in study part I) will be followed over a period of 3 years to evaluate the potential of LCI to detect early CLAD|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lung clearance index (LCI) | Measured by multiple breath nitrogen washout (Exhalyzer® D; Eco Medics AG) | Change from baseline up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in slope of acinar airways (Sacin) | Measured by multiple breath nitrogen washout (Exhalyzer® D; Eco Medics AG) | Change from baseline up to 3 years | 
| Change in slope of conducting airways (Scond) | Measured by multiple breath nitrogen washout (Exhalyzer® D; Eco Medics AG) | Change from baseline up to 3 years | 
| Change in forced expiratory volume in 1s (FEV1) | Measured by Spirometry (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in forced vital capacity (FVC) | Measured by Spirometry (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in forced expiratory flows at 25-75 of vital capacity (FEF25-75) | Measured by Spirometry (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in total lung capacity (TLC) | Measured by Bodyplethysmography (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in residual volume (RV) | Measured by Bodyplethysmography (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in total lung capacity (TLC) / residual volume (RV) ratio | Measured by Bodyplethysmography (Geratherm Respiratory GmbH) | Change from baseline up to 3 years | 
| Change in diffusing capacity for nitric oxide (DLNO) | Single-breath measurements (Jaeger MasterScreenTM PFT system) | Change from baseline up to 3 years | 
| Change in diffusing capacity for carbon monoxide oxide (DLCO) | Single-breath measurements (Jaeger MasterScreenTM PFT system) | Change from baseline up to 3 years | 
| Change in DLNO/DLCO ratio | Single-breath measurements (Jaeger MasterScreenTM PFT system) | Change from baseline up to 3 years | 
| Change in transfer coefficient for nitric oxide (DLNO/VA) | Single-breath measurements (Jaeger MasterScreenTM PFT system) | Change from baseline up to 3 years | 
| Change in transfer coefficient for carbon monoxide (DLCO/VA) | Single-breath measurements (Jaeger MasterScreenTM PFT system) | Change from baseline up to 3 years | 
| Change in computed tomography score | Measured by Computed Tomography: Semiquantative score (i.e., Brody Score); Subscores including bronchiectasis, mucus plugging, airway wall thickening, consolidation, mosaic pattern and air trapping). Subscores will be expressed as the percentage of the maximum score on a scale of 0 (no disease) to 100 (maximal lung disease). | Change from baseline up to 3 years |