Bronchial Inflammation of Small Airways in Patients With Cystic Fibrosis

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.

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