Evaluation of Bronchial Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA)

NCT00906568 | Completed

• 1 other identifier: KGU-32/09
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Cystic Fibrosis,

Keywords

Cystic fibrosis; Sensitization to Aspergillus; Bronchial allergen challenge; Induced Sputum; Bronchial inflammation; Small airways disease (SAD)

Outcome Measures

Primary Outcomes (1)

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

  1 year

Secondary Outcomes (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.

  1 year

Study Arms (1)

Sensitized vs non-sensitized

CF with and without SAD defined by MEF25 \<50%

Eligibility Criteria

• Age: 4 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• informed consent
• age between 4 and 45 years
• well-known Cystic fibrosis
• Lung function: FEV1 (% pred.) ≥ 70%

You may not qualify if:

• 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

Sponsors & Collaborators

• Johann Wolfgang Goethe University Hospital: lead

Study Sites (1)

Goethe-University Hospital

Frankfurt am Main, Hesse, 60590, Germany

Location

Related Publications (11)

• de Oliveira E, Giavina-Bianchi P, Fonseca LA, Franca AT, Kalil J. Allergic bronchopulmonary aspergillosis' diagnosis remains a challenge. Respir Med. 2007 Nov;101(11):2352-7. doi: 10.1016/j.rmed.2007.06.018. Epub 2007 Aug 3.

  PMID: 17689062 BACKGROUND

• Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. J Cyst Fibros. 2002 Jun;1(2):76-89. doi: 10.1016/s1569-1993(02)00033-4.

  PMID: 15463812 BACKGROUND

• Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G; Participants in the Cystic Fibrosis Foundation Consensus Conference. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64. doi: 10.1086/376525.

  PMID: 12975753 BACKGROUND

• Almeida MB, Bussamra MH, Rodrigues JC. ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens. J Pediatr (Rio J). 2006 May-Jun;82(3):215-20. doi: 10.2223/JPED.1479. Epub 2006 May 26.

  PMID: 16738737 BACKGROUND

• Skov M, Pressler T, Jensen HE, Hoiby N, Koch C. Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA). Thorax. 1999 Jan;54(1):44-50. doi: 10.1136/thx.54.1.44.

  PMID: 10343631 BACKGROUND

• D'Amato G. Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases. Eur J Pharmacol. 2006 Mar 8;533(1-3):302-7. doi: 10.1016/j.ejphar.2005.12.045. Epub 2006 Feb 7.

  PMID: 16464445 BACKGROUND

• Kauffman HF. Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodeling. Front Biosci. 2003 Jan 1;8:e190-6. doi: 10.2741/990.

  PMID: 12456379 BACKGROUND

• Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O'Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. doi: 10.1164/rccm.200708-1233OC. Epub 2007 Dec 13.

  PMID: 18079494 BACKGROUND

• Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, Locksley RM. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature. 2007 May 3;447(7140):92-6. doi: 10.1038/nature05746. Epub 2007 Apr 22.

  PMID: 17450126 BACKGROUND

• Seibold MA, Donnelly S, Solon M, Innes A, Woodruff PG, Boot RG, Burchard EG, Fahy JV. Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit. J Allergy Clin Immunol. 2008 Nov;122(5):944-950.e3. doi: 10.1016/j.jaci.2008.08.023. Epub 2008 Oct 9.

  PMID: 18845328 BACKGROUND

• Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA. Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science. 2004 Jun 11;304(5677):1678-82. doi: 10.1126/science.1095336.

  PMID: 15192232 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

serum: total Ig-E and RAST, sputum

MeSH Terms

Conditions

Cystic Fibrosis; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• Stefan Zielen, MD

  Goethe-University Frankfurt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 20, 2009
• First Posted: May 21, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: August 1, 2010
• Last Updated: February 16, 2011

Record last verified: 2010-10

Locations

DE (1)