Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

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).

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Key information

Conditions

Cystic Fibrosis, Chronic Disease Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystic Fibrosis Digestive System Diseases Disease Attributes Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Lung Diseases, Obstructive Pancreatic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases

Age range

4 year–45 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Goethe-University Hospital

Frankfurt am Main, Hesse, 60590, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

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

Time frame: 1 year

Secondary outcomes

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.

Sponsors and collaborators

Lead sponsor

Johann Wolfgang Goethe University Hospital

Other

Registry information

Official study title

Clinical Presentation and Bronchial Inflammation of Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis

Acronym: ABPA

Important dates

Study start: 2009
Primary completion: 2010
Study completion: 2010
First posted: May 21, 2009
Registry last updated: Feb 16, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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