LCI and Bronchial Inflammation in Patients With BO

Study Overview
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Brief Summary
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The investigators here compare lung function parameters (RV, RV/TLC and FEF75) with the results of the Lung Clearance index (LCI) . Further this study evaluates bronchial inflammatory markers in 20 patients with bronchiolitis obliterans at the age of 6 to 28 years compared with an age- and sex-matched control group. The investigators will perform a pulmonary function test (body plethysmography with DLCO) and compare the results with the LCI. Further we will measure the fraction of exhaled nitric oxide (FeNO) and draw a blood sample to determine the level of systemic inflammation. Finally induced sputum is collected and a cell count is performed, and cells and supernatants are analyzed for inflammatory markers. This study will set baseline markers for future interventional studies.

Detailed Description
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The purpose of this study is to compare lung function values with the Lung clearance index of 20 Patients with Bronchiolitis obliterans aged between 6 up to 28 years. Further we aim to compare the bronchial Inflammation between the patients and a reference group with similar age conditions to determine possible outcome-parameters for following interventional studies. The sputum samples will be processed and quantitatively analyzed to get a profile of the cytological composition. (Sputum and serum samples are analyzed by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) and by cytometric bead assay (CBA).) Methods and Work Programme: Measurement of nitric oxide in expired air (FeNO) Lung function testing with spirometry and body plethysmography Lung clearance index (LCI) Bronchodilation Blood test: blood count, CRP, RAST, serum inflammatory mediators, (genetic markers of the non-specific pulmonary defense system) Induced sputum for inflammatory mediators and microbiological investigations

Official Title
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Lung Clearance Index (LCI) and Bronchial Inflammation in Patients With Bronchiolitis Obliterans (BO)

Conditions
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Bronchiolitis Obliterans

Intervention / Treatment
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* Other: no intervention - just observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent between 6 and 28 years of age Known Bronchiolitis obliterans no Bronchiolitis obliterans(depending on the study group) Ability to perform lung function tests and inhalation Exclusion Criteria: Acute illness with systemic or bronchial inflammation every chronic condition or infection (eg HIV, tuberculosis, malignancy) pregnancy known alcohol and/ or drug abuse Inability to understand the extent and scope of the study Participation in another study

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 28 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subject-Group<br>Patients suffering from doctors diagnosed bronchiolitis obliterans | Other: no intervention - just observational<br> <br> |
| Control Group<br>age- and sex matched to subject-group | Other: no intervention - just observational<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LCI compared to RV/TLC%-pred. | Correlation of these lung function Parameters in patients with BO compared to healthy controls | during Visit 1 (single day, single observation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of sputum cell count over time (percentage of neutrophils) | induced sputum will be analyzed for different cellular components such as alveolar macrophages, neutrophils, lymphocytes and others. Epithelial cells will be excluded | during Visit 1 (single day, single observation) | 
| Comparison of low CrP | serum parameter for systemic inflammation | during Visit 1 (single day, single observation) | 
| FVC (%-pred.) | To compare FVC (%-pred.)of patients suffering from BO with FVC (%-pred.)of a healthy control group | during Visit 1 (single day, single observation) | 
| FEV1 (%-pred.) | To compare FEV1 (%-pred.)of patients suffering from BO withFEV1 (%-pred.)of a healthy control group | during Visit 1 (single day, single observation) | 
| Tiffeneau-Index | To compare Tiffeneau-Index of patients suffering from BO with Tiffeneau-Index of a healthy control group | during Visit 1 (single day, single observation) | 
| sRtot (%-pred.) | To compare sRtot (%-pred.) of patients suffering from BO with sRtot (%-pred.) of a healthy control group | during Visit 1 (single day, single observation) | 
| RV/TLC (%-pred.) | To compare RV/TLC (%-pred.) of patients suffering from BO with RV/TLC (%-pred.) of a healthy control group | during Visit 1 (single day, single observation) | 
| IL-6 (pg/ml) | comparing IL-6 in Serum of patients with BO with healthy controls | during Visit 1 (single day, single observation) | 
| IL-8 (pg/ml) | comparing IL-8 in Serum of patients with BO with healthy controls | during Visit 1 (single day, single observation)1 | 
| IL-17 (pg/ml) | comparing IL-17 in Serum of patients with BO with healthy controls | during Visit 1 (single day, single observation) | 
| IL-6 (mRNA delta-delta-ct) | compare IL-6 mRNA in Sputum cells of patients with BO with healthy controls | during Visit 1 (single day, single observation) | 
| IL-8 (mRNA delta-delta-ct) | compare IL-8 mRNA in Sputum cells of patients with BO with healthy controls | during Visit 1 | 
| IL-17 (mRNA delta-delta-ct) | compare IL-17 mRNA in Sputum cells of patients with BO with healthy controls | during Visit 1 (single day, single observation) | 
| Percentage of FOXP3 positive cells in Sputum | compare percentage of FOXP3 positive cells in Sputum cells of patients with BO with healthy controls | during Visit 1 (single day, single observation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sputum, bronchial inflammation, Bronchiolitis obliterans, Blood, Inflammation, adaptive immune system, innate immune system