LCI and Bronchial Inflammation in Patients With BO (FRABO-02)

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

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.

Study Overview

• Status: Completed
• Conditions: Bronchiolitis Obliterans
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Children's Hospital, Goethe-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 28 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from Bronchiolitis obliterans and controls

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

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)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 6, 2015
• First Submitted That Met QC Criteria: July 8, 2015
• First Posted (Estimate): July 13, 2015

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Inflammation; Blood; Sputum; Bronchiolitis obliterans; bronchial inflammation; adaptive immune system; innate immune system
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Inflammation; Bronchiolitis; Bronchiolitis Obliterans
• Other Study ID Numbers: EC 124/13