Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

Completed

• Conditions: Cystic Fibrosis,

• Registration Number: NCT00906568
• Lead Sponsor: Johann Wolfgang Goethe University Hospital

Brief 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.

Study Timeline

• Study Start: 2009-04
• Study First Submitted: 2009-05-20
• Study First Submitted QC: 2009-05-20
• Study First Posted: 2009-05-21
• Primary Completion: 2010-05
• Study Completion: 2010-08
• Status Verified: 2010-10
• Last Update Submitted: 2011-02-15
• Last Update Posted: 2011-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD)	1 year

Secondary Outcome Measures

Name	Time	Method
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.	1 year	In addition planned data analyze: CF-patients will be divided according to their involvement of small airway disease (SAD) into 2 groups: Group 1 without SAD with MEF25 \> 50%, Group 2 with SAD with MEF25 \< 50% and cell counts and pro-inflammatory cytokines (IL-5, IL-6, IL-8, IL-13, IL-17, INF) measured by quantitative RT-PCR and protein assay will be analyzed.

Trial Locations

Locations (1)

Goethe-University Hospital; 🇩🇪 Frankfurt, Hesse, Germany