Lung Function, LCI, Bronchial Inflammation and Epigenetics of Patients With BO (FRABO-03)

Lungfunction, Lung Clearance Index, Bronchial Inflammation and Epigenetics of Patients With Bronchiolitis Obliterans

Bronchiolitis obliterans is a chronic disease in which a persistent inflammatory process leads to obliteration of the small airways. Pulmonary function tests (body plethysmography with DLCO, lung clearance index) are performed and the fraction of exhaled nitric oxide is measured. A blood test is following to determine the inflammatory status und collect miRNA. Induced Sputum will be obtained.

Study Overview

• Status: Unknown
• Conditions: Bronchiolitis Obliterans
• Intervention / Treatment: Other: observation

Detailed Description

The purpose of this study is to compare miRNA pattern, lung function values, bronchial inflammation and the Lung clearance index of Patients with Bronchiolitis obliterans aged between 6 up to 30 years of age with a matched control group.

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 (qRT-PCR) and by cytometric bead assay (CBA). miRNA samples will be collected, processand compared with the miRNA database at http://www.mirbase.org/

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), miRNA analysis
• Induced sputum for inflammatory mediators and microbiological investigations

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Martin Rosewich, MD; Phone Number: 5381 +49-69-6301; Email: Martin.rosewich@kgu.de

Study Locations

• Germany
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Recruiting
      • Children's Hospital, Goethe-University
      • Contact: Martin Rosewich, MD; Phone Number: 5381 49-69-6301; Email: Martin.Rosewich@kgu.de
      • Contact: Stefan Zielen, MD, PhD; Phone Number: 83063 49-69-6301; Email: Stefan.Zielen@kgu.de
      • Principal Investigator: Martin Rosewich, MD
      • Sub-Investigator: Stefan Zielen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with the assured diagnose of Bronchiolitis Obliterans and controls without this disease.

Description

Inclusion Criteria:

• informed consent
• age between 6 an 35 years
• known bronchiolitis obliterans (Group Bronchiolitis)/ no Bronchiolitis Obliterans (Group matched controls)
• ability to perform lung function tests and inhale correctly

Exclusion Criteria:

• <6 years of age
• >35 years of age
• acute systemic or bronchial inflammation
• other chronic diseases or infection (e.g. HIV, Tbc, malignoma)
• pregnancy
• alcohol, drug or illegal drug abuse
• disability to register the range and consequences of the study
• actual participation in another study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subject Group; Patients suffering from Bronchiolitis Obliterans	Other: observation; Record lung function, Lung clearance index, inflammatory status
Control Group; Age and sex matched control group	Other: observation; Record lung function, Lung clearance index, inflammatory status

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
miRNA Status	Blood sample to determine candidate miRNA for Bronchiolitis obliterans	single day observation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung clearance index (LCI)	Determine Lung clearance index with the Oxygen washout method	single day observation
FVC [%-pred.]	Compare FVC [%-pred.] of BO Patients with a healthy control group	single day observation
FEV1 [%-pred.]	Compare FEV1[%-pred.] of BO Patients with a healthy control group	single day observation
Tiffeneau Index	Compare Tiffeneau-Index of BO Patients with a healthy control group	single day observation
sRtot [%-pred.]	Compare sRtot[%-pred.] of BO Patients with a healthy control group	single day observation
RV/TLC [%-pred.]	Compare RV/TLC[%-pred.] of BO Patients with a healthy control group	single day observation
DLCO [%-pred.]	Compare difffusion capacity of the lung for CO [%-pred.] of BO Patients with a healthy control group	single day observation
IL-6 (pg/ml)	Comparing IL-6 in Serum of patients with BO with a healthy control group	single day observation
IL-8 (pg/ml	Comparing IL-8 in Serum of patients with BO with a healthy control group	single day observation
Il-17 (pg/ml)	Comparing IL-17 in Serum of patients with BO with a healthy control group	single day observation
CrP (mg/dl)	Comparing CrP in Serum of patients with BO with a healthy control group	single day observation
FeNO ppb	Comparing FeNO in exhaled air of patients with BO with a healthy control group	single day observation
Sputum cell count	Comparing sputum cell counts of patients with BO with a healthy control group	single day 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

General Publications

• Kurland G, Michelson P. Bronchiolitis obliterans in children. Pediatr Pulmonol. 2005 Mar;39(3):193-208. doi: 10.1002/ppul.20145.
• Boehler A, Kesten S, Weder W, Speich R. Bronchiolitis obliterans after lung transplantation: a review. Chest. 1998 Nov;114(5):1411-26. doi: 10.1378/chest.114.5.1411. No abstract available.
• Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr. 2008 Jun;20(3):272-8. doi: 10.1097/MOP.0b013e3282ff62e9.
• 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. doi: 10.1002/ppul.1145.
• Rosewich M, Zissler UM, Kheiri T, Voss S, Eickmeier O, Schulze J, Herrmann E, Ducker RP, Schubert R, Zielen S. Airway inflammation in children and adolescents with bronchiolitis obliterans. Cytokine. 2015 May;73(1):156-62. doi: 10.1016/j.cyto.2014.10.026. Epub 2015 Mar 6.
• Motameny S, Wolters S, Nurnberg P, Schumacher B. Next Generation Sequencing of miRNAs - Strategies, Resources and Methods. Genes (Basel). 2010 Jun 3;1(1):70-84. doi: 10.3390/genes1010070.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: December 9, 2015
• First Submitted That Met QC Criteria: December 9, 2015
• First Posted (Estimate): December 11, 2015

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 9, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: inflammation; miRNA; chronic lung disease; lung clearance index; induced Sputum
• 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: MRosewich