Clinical trial NCT01479166: Bronchial Inflammation of Small Airways in Patients With Cystic Fibrosis
Official title: Bronchial Inflammation of Small Airways in Patients With Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
HRCT
Sputum
Blood
Inflammation
adaptive immune system
innate immune system
Lead sponsor: Johann Wolfgang Goethe University Hospital
Sponsor class: OTHER
First posted: 2011-11-24
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study is carried out in CF children and adults (6 to 60 years) and healthy controls (6-60 years). Both patients (40) and healthy subjects (20) are recruited from the Christiane Herzog CF outpatient clinic of Johann Wolfgang Goethe-University, Frankfurt/M, Germany.

Brief summary: In the planned study, 60 patients with mild cystic fibrosis (CF) with and without the involvement of small airways (small airway disease - SAD) are to be compared with a historical control group matched in age and gender. During the first study visit subjects are asked to perform a pulmonary function test (spirometry, body plethysmography with helium, determination of "Trapped Air") and exhaled nitric oxide (eNO) and exhaled carbon monoxide (eCO) measurements will be done in exhaled air. In addition, a blood sample is drawn to describe inflammatory status. Sputum is induced as well. During the second study visit, a non-specific bronchial provocation test(methacholine PD20 FEV1) is performed.

The aim of the study is to get a characterization of the bronchial and systemic inflammation (IL-1ß, IL-6, IL-8, IL-17, TNF-α, NFKB, and recognition structures like TLR2 and TLR4) in CF patients with and without the involvement of the small airways, which may point to new treatment strategies.

Detailed description: Aim of this study is the characterization of patients with mild cystic fibrosis in terms of lung function, bronchial hyperreactivity and the degree of systemic and bronchial inflammation.

Sputum and serum samples are analyzed by quantitative real-time polymerase chain reaction(qRT-PCR) and by cytometric bead assay (CBA). Components of the innate immune system (mannose-binding protein, TLR recognition proteins and surfactant proteins) are genetically determined from sputum or blood respectively. In order to support the analyzed lung function and sputum/ serum biomarker data the investigators will also rely on pre-existing imaging data like chest x-rays or high-resolution computer tomography (HRCT)of the lungs.

Methods and Work Programme:

This study consists of two study visits (V1 and V2)

V1:

Measurement of nitric oxide in exhaled air (eNO) Measurement of carbon monoxide in exhaled air (eCO) Lung function testing with spirometry and body plethysmography 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

V2:

Unspecific bronchial provocation test with methacholine (PD20 FEV1 methacholine) Lung function testing with spirometry and body plethysmography

Study population:

CF Children and adults (6 - 60 years of age) and a healthy control group (6-60 years of age). Both patients and healthy subjects are recruited from the Christiane Herzog Cystic fibrosis outpatient clinic.

Eligibility criteria: Inclusion Criteria:

* informed consent
* confirmed diagnosis of CF (known mutations and/or sweat chloride test \> 60mval/l)
* age between 6 and 60 years
* vital capacity \> 75%
* Ability to perform lung function tests and inhalation

Exclusion Criteria:

* \< 6 and \> 60 years of age on the day of written informed consent
* 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

Primary outcomes:
measure: Bronchial Inflammation in sputum of patients with CF
timeFrame: 24 months
Secondary outcomes:
measure: Inflammatory proteins like (Il-1,IL-6, TNF alpha) in induced sputum
timeFrame: 24 months
Other outcomes:
Locations:
city: Frankfurt am Main
country: Germany
facility: Children's Hospital, Johann Wolfgang Goethe-University
state: Hesse
Study officials:
affiliation: Children´s Hospital of Johann Wolfgang Goethe-Univeristy, Frankfurt/Main
name: Stefan Zielen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, Buhl R, Schmitt-Grohe S, Zielen S, Schubert R. Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Cytokine. 2010 May;50(2):152-7. doi: 10.1016/j.cyto.2010.02.004. Epub 2010 Feb 23.
citation: Tiddens HA, Donaldson SH, Rosenfeld M, Pare PD. Cystic fibrosis lung disease starts in the small airways: can we treat it more effectively? Pediatr Pulmonol. 2010 Feb;45(2):107-17. doi: 10.1002/ppul.21154.