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

February 15, 2011 updated by: Johann Wolfgang Goethe University Hospital

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).

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Hesse
      • Frankfurt, Hesse, Germany, 60590
        • Goethe-University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 45 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johann Wolfgang Goethe University Hospital

Investigators

  • Principal Investigator: Stefan Zielen, MD, Goethe-University Frankfurt

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (ACTUAL)

May 1, 2010

Study Completion (ACTUAL)

August 1, 2010

Study Registration Dates

First Submitted

May 20, 2009

First Submitted That Met QC Criteria

May 20, 2009

First Posted (ESTIMATE)

May 21, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

February 16, 2011

Last Update Submitted That Met QC Criteria

February 15, 2011

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KGU-32/09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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