Bronchial Inflammation in Patients With Severe Immune Deficiency Under Immunoglobulin Treatment

The purpose of the clinical trial is to gain a more substantial understanding of bronchial inflammation in patients with severe primary immundeficiency under immunoglobulin therapy. It is intended to characterize the systemical such as the bronchial inflammation (IL-1, IL-2, IL-6, IL-8, IL-17, TNF-a, NFkB, IFN-gamma, TGF-beta, TLR2 und TLR4)in children with severe immune deficiency in order to generate new treatment strategies based on the results.

The methods being used for characterization purposes within this trial include specific lung function tests ( spirography, bodyplethysmographie w. helium) such as the analysis of eNO and eCO. Furthermore, sputum and serum samples are being analyzed by quantitative real-time polymerase chain reaction (PCR),(qRT-PCR) and by cytometric bead assay (CBA). Components of the innate immune system (mannose-binding protein, TLR recognition proteins and surfactant proteins) are genetically determined from sputum or blood respectively. In the conduct of the study the investigators will retrospectively and systematically evaluate the available high-resolution computed tomography (HRCT) studies of affected patients.

Study Overview

• Status: Unknown
• Conditions: Immune Deficiency

Detailed Description

The clinical trial contains a patient collective of 50 (6-60 years of age) that shall be eventually compared to a control group equal in age and gender. Both the patients and the healthy subjects are recruited from the outpatient clinic of Pediatric Allergy and Pulmonology.

Methods and Work Programme:

This study consists of two study visits (V1 and V2)

V1:

• Measurement of nitric oxide in expired air (eNO)
• Measurement of carbon monoxide in the exhaled air (eCO)
• Lung function testing with spirography and bodyplethysmographie
• Blood test: blood count, CRP, RAST, serum inflammatory mediators, genetic markers of the non-specific pulmonary defense system
• Induced sputum for inflammatory mediators and microbiological investigations

V2:

*Unspecific bronchial provocation test with methacholine (PD20 FEV1 metacholine)

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Frankfurt a. Main, Hessen, Germany, 60590
      • Children's Hospital, Goethe-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study is carried out in children and young adults (6-60 years of age). Both the patients (25) and the healthy subjects (25) are recruited from the outpatient clinic of the departement of Pediatric Allergy and Pulmonology and the departement of Pediatric Immune deficiency , University Clinic, JW Goethe University, Frankfurt/M, Germany

Description

Inclusion Criteria:

• informed consent
• 6 to 60 years of age
• known severe immune deficiency under immunoglobulin therapy/ no immune deficiency ( depending on study group)
• ability to perform lung function tests and inhalation

Exclusion Criteria:

• < 6 and > 60 years of age on the day of written informed consent
• acute illness with systemic or bronchial inflammation
• every chronic condition or infection (e.g. HIV, tuberculosis, malignancy)
• pregnancy
• known alcohol and/ or drug abuse
• Inability to understand the extent and scope of the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
affected patients; 25 patients suffering from severe immune deficiency under immunoglobulin therapy
non-affected patients; 25 matched controls not suffering from severe immune deficiency

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital

Publications and helpful links

General Publications

• Eickmeier O, Huebner M, Herrmann E, Zissler U, Rosewich M, Baer PC, Buhl R, Schmitt-Grohe S, Zielen S, Schubert R. Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Cytokine. 2010 May;50(2):152-7. doi: 10.1016/j.cyto.2010.02.004. Epub 2010 Feb 23.
• Sweinberg SK, Wodell RA, Grodofsky MP, Greene JM, Conley ME. Retrospective analysis of the incidence of pulmonary disease in hypogammaglobulinemia. J Allergy Clin Immunol. 1991 Jul;88(1):96-104. doi: 10.1016/0091-6749(91)90306-9.
• de Gracia J, Vendrell M, Alvarez A, Pallisa E, Rodrigo MJ, de la Rosa D, Mata F, Andreu J, Morell F. Immunoglobulin therapy to control lung damage in patients with common variable immunodeficiency. Int Immunopharmacol. 2004 Jun;4(6):745-53. doi: 10.1016/j.intimp.2004.02.011.
• Touw CM, van de Ven AA, de Jong PA, Terheggen-Lagro S, Beek E, Sanders EA, van Montfrans JM. Detection of pulmonary complications in common variable immunodeficiency. Pediatr Allergy Immunol. 2010 Aug;21(5):793-805. doi: 10.1111/j.1399-3038.2009.00963.x. Epub 2009 Nov 13.
• Buehring I, Friedrich B, Schaaf J, Schmidt H, Ahrens P, Zielen S. Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies. Clin Exp Immunol. 1997 Sep;109(3):468-72. doi: 10.1046/j.1365-2249.1997.4831379.x.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): May 1, 2012
• Study Completion (Anticipated): May 1, 2012

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 23, 2011
• First Posted (Estimate): May 24, 2011

Study Record Updates

• Last Update Posted (Estimate): May 24, 2011
• Last Update Submitted That Met QC Criteria: May 23, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: severe primary immune deficieny
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: KGU 84-11