Cystic Fibrosis, Clinical Trial
Official title:
Clinical Presentation and Bronchial Inflammation of Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis
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).
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