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Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

This study has been completed.
Sponsor:
Information provided by:
Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT00906568
First received: May 20, 2009
Last updated: February 15, 2011
Last verified: October 2010
  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

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome 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 ] [ 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
Study Population

Outpatients of Department of cystic fibrosis, Goethe University, Frankfurt, Germany

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906568

Locations
Germany
Goethe-University Hospital
Frankfurt, Hesse, Germany, 60590
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Investigators
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
Dermatomycoses
Digestive System Diseases
Genetic Diseases, Inborn
Hyalohyphomycosis
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Infant, Newborn, Diseases
Infection
Lung Diseases
Lung Diseases, Fungal
Mycoses
Pancreatic Diseases
Pathologic Processes
Respiratory Hypersensitivity
Respiratory Tract Diseases
Respiratory Tract Infections
Skin Diseases
Skin Diseases, Infectious

ClinicalTrials.gov processed this record on November 20, 2014