Nachweis von Alpha-1-Antitrypsin in exhaliertem Atemwegskondensat

Der Alpha-1-Antitrypsin-Mangel (AAT-Mangel) ist eine genetische Erkrankung, die den Träger für die Entwicklung einer chronisch obstruktiven Lungenerkrankung (COPD) sowie einer Leberzirrhose prädisponiert. Die Hauptfunktion von Alpha-1-Antitrypsin besteht darin, das Lungengewebe gegen den Einfluss vo...

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Bibliographic Details
Main Author: Noeske, Sarah
Contributors: Bals, Robert (Prof. Dr. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2011
Online Access:PDF Full Text
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Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that predisposes to chronic obstructive pulmonary disease (COPD) and liver cirrhosis. The main function of alpha-1-antitrypsin (AAT) is to protect the lungs against neutrophil elastase. It is difficult to measure the levels of AAT in different compartments of the lung. Bronchoscopy is still the gold standard to assess the lower respiratory tract and the epithelial lining fluid (ELF). Measurement of exhaled breath condensate (EBC) is a non invasive method to investigate parameters of the epithelial lining fluid of the lung and to detect changes in physiological homeostasis. It was the aim of the study to show that AAT is measurable with the non invasive method of EBC. An AAT-ELISA and AAT-Western Blot were standardized to detect very small amounts of AAT in EBC. AAT was also measurable in patients with AATD. No correlation could be found between AAT-serum-levels and AAT-levels in EBC. A further aim of this study was to compare AAT-levels in EBC of healthy controls (HC), patients with stable and exacerbated COPD as well as augmented and non-augmented patients with AATD. Patients with exacerbated COPD had significantly increased AAT-values compared to HCs and patients with stable COPD. Augmented patients with AATD had also significantly higher AAT-values in EBC compared to HCs and patients with stable COPD. Furthermore, non augmented AATD-patients showed significantly higher AAT-values compared with augmented AATD-patients. In a final step pH- and interleukin-8-values (IL-8) as markers of pulmonary inflammation were measured in EBC from patients with stable and exacerbated COPD, augmented and non augmented patients with AATD and from healthy controls. Patients with stable and exacerbated COPD showed significantly lower pH-values compared to HCs. IL-8-values in EBC of patients with AATD were significantly higher than in patients with COPD and HCs. In conclusion we found EBC collection is extremely simple to perform, non invasive, inexpensive and reproducible. Therefore, it is well-suited for non invasive analysis in longitudinal follow-ups and individual monitoring of patients with chronicle disease. It could be shown that AAT has an important role as acute-phase-protein and marker of inflammation. Especially in inflammatory processes of the lung it has major impact. More standardization work must be done to improve the method of EBC for future approach.