Bronchial Inflammation of Small Airways in Patients With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis; Inflammation
Study type: Observational

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.
    

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.
      
Biospecimen description: 
      whole blood, serum and Sputum
    
Keywords: cystic fibrosis; HRCT; Sputum; Blood; Inflammation; adaptive immune system; innate immune system