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Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA) (ABPA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00906568
Recruitment Status : Completed
First Posted : May 21, 2009
Last Update Posted : February 16, 2011
Information provided by:
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).

Condition or disease
Cystic Fibrosis,

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.

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Study Type : Observational
Actual Enrollment : 40 participants
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
Study Start Date : April 2009
Actual Primary Completion Date : May 2010
Actual Study Completion Date : August 2010

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

Primary Outcome Measures :
  1. The characterization of patients with CF and sensitization to Aspergillus fumigatus, and analyzing involvement of small airway disease (SAD) [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. 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 ]
    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

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Ages Eligible for Study:   4 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00906568

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Goethe-University Hospital
Frankfurt, Hesse, Germany, 60590
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
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Principal Investigator: Stefan Zielen, MD Cooperative Weichteilsarkom Study Group


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Responsible Party: Prof. Dr. Stefan Zielen, Children´s Hospital, Department of Allergy, Pulmunology and Cystic Fibrosis, Goethe University, Frankfurt, Germany Identifier: NCT00906568     History of Changes
Other Study ID Numbers: KGU-32/09
First Posted: May 21, 2009    Key Record Dates
Last Update Posted: February 16, 2011
Last Verified: October 2010

Keywords provided by Johann Wolfgang Goethe University Hospital:
Cystic fibrosis
Sensitization to Aspergillus
Bronchial allergen challenge
Induced Sputum
Bronchial inflammation
Small airways disease (SAD)

Additional relevant MeSH terms:
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Pulmonary Aspergillosis
Aspergillosis, Allergic Bronchopulmonary
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases, Fungal
Respiratory Hypersensitivity
Respiratory Tract Infections
Hypersensitivity, Immediate
Immune System Diseases