FRABO-02: LCI and Bronchial Inflammation in Patients With BO

• Sponsor: Johann Wolfgang Goethe University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02495597
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Duration (Months): 20
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bronchiolitis Obliterans	Other: no intervention - just observational

Detailed Description

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

Study Design

• Study Type: Observational
• Actual Enrollment: 37 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Lung Clearance Index (LCI) and Bronchial Inflammation in Patients With Bronchiolitis Obliterans (BO)
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. LCI compared to RV/TLC%-pred. [during Visit 1 (single day, single observation)]

   Correlation of these lung function Parameters in patients with BO compared to healthy controls

Secondary Outcome Measures

1. change of sputum cell count over time (percentage of neutrophils) [during Visit 1 (single day, single observation)]

   induced sputum will be analyzed for different cellular components such as alveolar macrophages, neutrophils, lymphocytes and others. Epithelial cells will be excluded

2. Comparison of low CrP [during Visit 1 (single day, single observation)]

   serum parameter for systemic inflammation

3. FVC (%-pred.) [during Visit 1 (single day, single observation)]

   To compare FVC (%-pred.)of patients suffering from BO with FVC (%-pred.)of a healthy control group

4. FEV1 (%-pred.) [during Visit 1 (single day, single observation)]

   To compare FEV1 (%-pred.)of patients suffering from BO withFEV1 (%-pred.)of a healthy control group

5. Tiffeneau-Index [during Visit 1 (single day, single observation)]

   To compare Tiffeneau-Index of patients suffering from BO with Tiffeneau-Index of a healthy control group

6. sRtot (%-pred.) [during Visit 1 (single day, single observation)]

   To compare sRtot (%-pred.) of patients suffering from BO with sRtot (%-pred.) of a healthy control group

7. RV/TLC (%-pred.) [during Visit 1 (single day, single observation)]

   To compare RV/TLC (%-pred.) of patients suffering from BO with RV/TLC (%-pred.) of a healthy control group

8. IL-6 (pg/ml) [during Visit 1 (single day, single observation)]

   comparing IL-6 in Serum of patients with BO with healthy controls

9. IL-8 (pg/ml) [during Visit 1 (single day, single observation)1]

   comparing IL-8 in Serum of patients with BO with healthy controls

10. IL-17 (pg/ml) [during Visit 1 (single day, single observation)]

    comparing IL-17 in Serum of patients with BO with healthy controls

11. IL-6 (mRNA delta-delta-ct) [during Visit 1 (single day, single observation)]

    compare IL-6 mRNA in Sputum cells of patients with BO with healthy controls

12. IL-8 (mRNA delta-delta-ct) [during Visit 1]

    compare IL-8 mRNA in Sputum cells of patients with BO with healthy controls

13. IL-17 (mRNA delta-delta-ct) [during Visit 1 (single day, single observation)]

    compare IL-17 mRNA in Sputum cells of patients with BO with healthy controls

14. Percentage of FOXP3 positive cells in Sputum [during Visit 1 (single day, single observation)]

    compare percentage of FOXP3 positive cells in Sputum cells of patients with BO with healthy controls

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 28 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital, Goethe-University	Frankfurt am Main	Hessen	Germany	60590

Sponsors and Collaborators

• Johann Wolfgang Goethe University Hospital

Investigators

• Principal Investigator: Martin Rosewich, MD, Johann Wolfgang Goethe University Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Kurland G, Michelson P. Bronchiolitis obliterans in children. Pediatr Pulmonol. 2005 Mar;39(3):193-208. Review
• Smith KJ, Fan LL. Insights into post-infectious bronchiolitis obliterans in children. Thorax. 2006 Jun;61(6):462-3.
• Pichler M, Herrmann G, Schmidt H, Ahrens P, Zielen S. Persistent adenoviral infection and chronic obstructive bronchitis in children: is there a link? Pediatr Pulmonol. 2001 Nov;32(5):367-71.
• Pichler MN, Reichenbach J, Schmidt H, Herrmann G, Zielen S. Severe adenovirus bronchiolitis in children. Acta Paediatr. 2000 Nov;89(11):1387-9.

Publications

None provided.

• Responsible Party: Dr. med. Martin Rosewich, Principal Investigator, Johann Wolfgang Goethe University Hospital
• ClinicalTrials.gov Identifier: NCT02495597
• Other Study ID Numbers: EC 124/13
• First Posted: Jul 13, 2015
• Last Update Posted: Jul 23, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Dr. med. Martin Rosewich, Principal Investigator, Johann Wolfgang Goethe University Hospital: bronchial inflammation; Bronchiolitis obliterans; Sputum; Blood; Inflammation; adaptive immune system; innate immune system
• Additional relevant MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Inflammation

Study Results

No Results Posted as of Jul 23, 2015