Clinical trial NCT02627833: Lung Function, LCI, Bronchial Inflammation and Epigenetics of Patients With BO
Official title: Lungfunction, Lung Clearance Index, Bronchial Inflammation and Epigenetics of Patients With Bronchiolitis Obliterans
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bronchiolitis Obliterans
Keywords: induced Sputum
lung clearance index
miRNA
inflammation
chronic lung disease
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2015-12-11
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with the assured diagnose of Bronchiolitis Obliterans and controls without this disease.

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: miRNA Status
timeFrame: single day observation
Secondary outcomes:
Other outcomes:
measure: Lung clearance index (LCI)
timeFrame: single day observation
measure: FVC [%-pred.]
timeFrame: single day observation
measure: FEV1 [%-pred.]
timeFrame: single day observation
measure: Tiffeneau Index
timeFrame: single day observation
measure: sRtot [%-pred.]
timeFrame: single day observation
measure: RV/TLC [%-pred.]
timeFrame: single day observation
measure: DLCO [%-pred.]
timeFrame: single day observation
measure: IL-6 (pg/ml)
timeFrame: single day observation
measure: IL-8 (pg/ml
timeFrame: single day observation
measure: Il-17 (pg/ml)
timeFrame: single day observation
measure: CrP (mg/dl)
timeFrame: single day observation
measure: FeNO ppb
timeFrame: single day observation
measure: Sputum cell count
timeFrame: single day observation
Locations:
city: Frankfurt am Main
country: Germany
facility: Children's Hospital, Goethe-University
state: Hessen
Study officials:
affiliation: Johann Wolfgang Goethe University Hospital
name: Martin Rosewich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kurland G, Michelson P. Bronchiolitis obliterans in children. Pediatr Pulmonol. 2005 Mar;39(3):193-208. doi: 10.1002/ppul.20145.
citation: 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.
citation: Moonnumakal SP, Fan LL. Bronchiolitis obliterans in children. Curr Opin Pediatr. 2008 Jun;20(3):272-8. doi: 10.1097/MOP.0b013e3282ff62e9.
citation: 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.
citation: 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.
citation: 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.