Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)
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Purpose
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).
| Condition |
|---|
|
Cystic Fibrosis, |
| Study Type: | Observational |
| Study Design: | Observational Model: Case-Only Time Perspective: Cross-Sectional |
| Official Title: | Clinical Presentation and Bronchial Inflammation of Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis |
- The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]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.
Biospecimen Retention: Samples With DNA
serum: total Ig-E and RAST, sputum
| Enrollment: | 40 |
| Study Start Date: | April 2009 |
| Study Completion Date: | August 2010 |
| Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
| Groups/Cohorts |
|---|
|
Sensitized vs non-sensitized
CF with and without SAD defined by MEF25 <50%
|
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.
Eligibility| Ages Eligible for Study: | 4 Years to 45 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Outpatients of Department of cystic fibrosis, Goethe University, Frankfurt, Germany
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
Contacts and Locations| Germany | |
| Goethe-University Hospital | |
| Frankfurt, Hesse, Germany, 60590 | |
| Principal Investigator: | Stefan Zielen, MD | Cooperative Weichteilsarkom Study Group |
More Information
Publications:
| Responsible Party: | Prof. Dr. Stefan Zielen, Children´s Hospital, Department of Allergy, Pulmunology and Cystic Fibrosis, Goethe University, Frankfurt, Germany |
| ClinicalTrials.gov Identifier: | NCT00906568 History of Changes |
| Other Study ID Numbers: | KGU-32/09 |
| Study First Received: | May 20, 2009 |
| Last Updated: | February 15, 2011 |
| Health Authority: | Germany: Ethics Commission |
Keywords provided by Johann Wolfgang Goethe University Hospitals:
|
Cystic fibrosis Sensitization to Aspergillus Bronchial allergen challenge |
Induced Sputum Bronchial inflammation Small airways disease (SAD) |
Additional relevant MeSH terms:
|
Aspergillosis Aspergillosis, Allergic Bronchopulmonary Cystic Fibrosis Fibrosis Inflammation Pulmonary Aspergillosis Mycoses Lung Diseases, Fungal Lung Diseases Respiratory Tract Diseases |
Respiratory Hypersensitivity Respiratory Tract Infections Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Pancreatic Diseases Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on June 18, 2013