Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

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.

Arms, Groups and Cohorts in this Clinical Trial

• : Sensitized vs non-sensitized
  • CF with and without SAD defined by MEF25 <50%

Primary Measures

• The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD)
  • Time Frame: 1 year
    Safety Issue?: Yes

Secondary Measures

• Aspergillus-induced inflammation in sputum using new mediators (IL-8, IL-13, TLR2 and TLR4, LBP and Chitinasen) with the quantitative PCR and protein assay analysis.
  • Time Frame: 1 year
    Safety Issue?: No

Inclusion Criteria:

• informed consent
• age between 4 and 45 years
• well-known Cystic fibrosis
• Lung function: FEV1 (% pred.) ≥ 70%

Exclusion Criteria:

• age < 4 and > 45 years
• lung function: FEV1 (% pred.)< 70%
• other chronic diseases or infections (e.g., HIV, tuberculosis, malignancy)
• pregnancy
• known alcohol, drug and/or drug abuse
• inability to capture the scale and scope of the study
• participation in another study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 4 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Johann Wolfgang Goethe University Hospitals Other

Overall Clinical Trial Officials and Contacts

Stefan Zielen, MD Principal Investigator Cooperative Weichteilsarkom Study Group  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00906568

Study ID Number: KGU-32/09

ClinicalTrials.gov Identifier: NCT00906568

Health Authority: Germany: Ethics Commission