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.

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)

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

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