Change in Airway Peripheral Tone in COPD

Study Overview
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Brief Summary
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Small airways disease is a pathological feature in mild to moderate COPD, which might be causally involved in disease progression. However, there are only limited studies available that prospectively identified patients at risk for small airway disease. Our intention is to investigate the early phase of the disease. In addition, we thereby want to build up a well-defined study population of patients in an early phase of the disease with a rapid decrease in lung function as measured by oscillometry and multiple breath washout (MBW)-testing. In addition, it is our goal to identify patients in an early stage of disease and patients at risk of fast progression and/or rapid decline in lung function.

Official Title
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Role of Small Airway Dysfunction for Disease Progression in Early COPD - an Observational Two-year Study

Conditions
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COPD, COPD, Early-Onset

Intervention / Treatment
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* Diagnostic Test: oscillometry
* Diagnostic Test: multiple breath washout testing
* Diagnostic Test: spirometry
* Diagnostic Test: body plethysmography
* Diagnostic Test: fractional exhaled nitric oxide
* Diagnostic Test: transfer factor
* Diagnostic Test: health status
* Diagnostic Test: computed tomography
* Diagnostic Test: induced sputum


Participation Criteria
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Eligibility Criteria
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patients at risk for COPD inclusion criteria: smoking history (at least 10 pack years) absence of airway obstruction (FEV1/FVC ≥ 70% after salbutamol 400µg) high symptom score (CAT ≥ 10) or long acting bronchodilator therapy age > 35 years exclusion criteria: respiratory infection within 4 weeks prior to inclusion other symptomatic pulmonary disease, except bronchial asthma patients with early COPD inclusion criteria: smoking history (at least 10 pack years) mild COPD (FEV1/FVC < 70% and FEV1 ≥ 70% after salbutamol 400µg) age > 35 years exclusion criteria: respiratory infection within 4 weeks prior to inclusion other pulmonary disease, except bronchial asthma

Ages Eligible for Study
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Minimum Age: 35 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 early COPD<br>diagnosis according to current GOLD recommendations | Diagnostic Test: oscillometry<br>* assessment of peripheral airway resistance using oscillometry<br>Diagnostic Test: multiple breath washout testing<br>* assessment of ventilation heterogeneity using multiple breath washout testing<br>Diagnostic Test: spirometry<br>* assessment of lung function using spirometry<br>Diagnostic Test: body plethysmography<br>* assessment of lung function using body plethysmography<br>Diagnostic Test: fractional exhaled nitric oxide<br>* assessment of eosinophilic airway inflammation using fractional exhaled nitric oxide<br>Diagnostic Test: transfer factor<br>* assessment of gas transfer using single breath transfer factor for carbon monoxide<br>Diagnostic Test: health status<br>* assessment of health status using validated questionnaires (St. George's Respiratory Questionnaire [SGRQ], COPD Assessment Test [CAT])<br>Diagnostic Test: computed tomography<br>* assessment of lung structure and function using computed tomography (only in patients with clinical indication, Heidelberg site)<br>Diagnostic Test: induced sputum<br>* various biomarkers (subgroup of approximately 75 patients, Großhansdorf site)<br>|
| patients at risk for COPD<br>no current diagnosis according to GOLD recommendations, but at risk for COPD | Diagnostic Test: oscillometry<br>* assessment of peripheral airway resistance using oscillometry<br>Diagnostic Test: multiple breath washout testing<br>* assessment of ventilation heterogeneity using multiple breath washout testing<br>Diagnostic Test: spirometry<br>* assessment of lung function using spirometry<br>Diagnostic Test: body plethysmography<br>* assessment of lung function using body plethysmography<br>Diagnostic Test: fractional exhaled nitric oxide<br>* assessment of eosinophilic airway inflammation using fractional exhaled nitric oxide<br>Diagnostic Test: transfer factor<br>* assessment of gas transfer using single breath transfer factor for carbon monoxide<br>Diagnostic Test: health status<br>* assessment of health status using validated questionnaires (St. George's Respiratory Questionnaire [SGRQ], COPD Assessment Test [CAT])<br>Diagnostic Test: computed tomography<br>* assessment of lung structure and function using computed tomography (only in patients with clinical indication, Heidelberg site)<br>Diagnostic Test: induced sputum<br>* various biomarkers (subgroup of approximately 75 patients, Großhansdorf site)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| oscillometry (change in R5-20) | change in frequency dependence of resistance (R5-20) | 24 months | 
| multiple breath washout testing (change in LCI) | change in global ventilation heterogeneity (lung clearance index, LCI) | 24 months | 
| multiple breath washout testing (change in Scond) | change in conductive ventilation heterogeneity (Scond) | 24 months | 
| multiple breath washout testing (change in Sacin) | change in acinar ventilation heterogeneity (Sacin) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| spirometry (change in FEV1) | change in parameters of central obstruction (forced expiratory volume in one second, FEV1) | 24 months | 
| body plethysmography (change in RV/TLC) | change in parameters of hyperinflation (residual volume / total lung capacity RV/TLC) | 24 months | 
| body plethysmography (change in sRaw) | change in specific airway resistance (sRaw) | 24 months | 
| health Status (change in SGRQ-c) | change in quality of life (SGRQ-c) | 24 months | 
| health Status (change in CAT) | change in symptom score (CAT) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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small airway disease, peripheral airway tone