Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)
Condition: Cystic Fibrosis,
MeSH terms: Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Fibrosis; Inflammation
Study type: Observational

Summary: 
      Chronic bronchial inflammation is an important clinical feature in cystic fibrosis.
      Approximately 10% of patients with cystic fibrosis suffer from Allergic Bronchopulmonary
      Aspergillosis. In addition airway inflammation in patients with cystic fibrosis (CF) plays a
      major role in progression of CF lung disease. In patients with mild disease (Vital capacity
      >75%) airway inflammation is often under diagnosed.

      Severity of allergy against Aspergillus fumigatus will be examined using radioallergosorbent
      test and skin Prick-test. Subsequently, in patients with established sensitization (RAST ≥
      0.35 IU/mL) a specific bronchial provocation with Aspergillus will be performed. In addition,
      exhaled nitric oxide,carbon monoxide, exhaled air temperature and inflammatory cells in
      sputum is measured. 24 hours after bronchial allergen provocation, exhaled NO, CO, air
      temperature, and bronchial responsiveness is determined and a second sputum obtained.

      This study is designed to characterize patients with CF and sensitization against Aspergillus
      fumigatus in an early stage to prevent pulmonary complications of ABPA. In addition sputum
      cytokine profiles in CF patients with mild and moderate disease may be different in patients
      without and with involvement of small airway disease (SAD).
    

Detailed description: 
      Since symptoms of Bronchopulmonary Aspergillosis are often identical to bacterial infections,
      the diagnosis is difficult to make. The disease presents with wheezing, pulmonary
      infiltrates, and bronchiectasis. The most important diagnostic parameters are asthmatic
      symptoms with obstruction, positive prick test, elevated total IgE, specific IgE and IgG to
      Aspergillus fumigatus, eosinophilia and radiological findings. Aspergillus fumigatus acts as
      an allergen Ig-E mediated allergy. Pathophysiological it is assumed that there are two
      different mechanisms of allergic inflammation. First, there is a direct effect of Aspergillus
      fumigatus proteases in the alveolar and bronchial epithelium with release of proinflammatory
      cytokines (IL-8, IL6, MCP-1) and consecutive chemotaxis of inflammatory cells. Second a CD4+
      Th2 response with release of IL-4, IL-5 and IL-13. Recently published studies suggest that
      Aspergillus spores cause the TH2-dependent inflammation directly. So-called Chitinases (part
      of innate immunity) induce massive IL-13 stimulation. Induction of chitinase activity (CHIT1)
      leads to an increased remodeling of the lung. It is currently unclear, to which extent
      Aspergillus-triggered bronchial inflammation in patients with CF is relevant.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Outpatients of Department of cystic fibrosis, Goethe University, Frankfurt, Germany
      
Biospecimen description: 
      serum: total Ig-E and RAST, sputum
    
Keywords: Cystic fibrosis; Sensitization to Aspergillus; Bronchial allergen challenge; Induced Sputum; Bronchial inflammation; Small airways disease (SAD)