In close cooperation with the children allergy and pneumolgy department of the Goethe University Frankfurt we have developed specialised bronchial provocation models to study allergen- and LPS- induced inflammation in healthy individuals and disease volunteers.
Allergen Provocation Models
Stepwise Allergen Challenge
Specific bronchial hyperreactivity (BHR) will be assessed using inhalation of allergen solution until a 20% fall in FEV1 occurs (Rosewich et al.). The allergen solution will be delivered via a medic aid nebulizer and the aerosol provocation system APS® powered by compressed air (by VIASYS Healthcare GmbH, Hoechberg, Germany). This system calculates the administered dose by breath from a constant flow and the inspiration time of any breath cycle, thus calculating the exact dose to be administered automatically.
Single dose allergen challenge
Baseline and saline procedures are the same as the stepwise challenge. The subject is challenged with a dose derived from the cumulative dose administered in the preceding stepwise challenge using the equation above. If FEV1 falls 15% or more the patient will have this value recorded as their baseline FEV1 response to allergen challenge and can proceed to dosing with given study medication.
Low dose allergen provocation
This well established method using a non cumulative dose of allergen causing a fall in FEV1 of 5% will be used for repeated allergen exposure to induce a chronic inflammatory response. The low dose allergen provocation model is a perfect tool to study the anti-inflammatory effect of new compounds and of functional foods (Schubert et al).
Inhaling bacterial endotoxin and its derivative LPS can induce a distinct inflammatory response, varying among hosts1 . Experimental LPS-inhalation is an established procedure in inflammation research. We have recently shown that LPS-challenge is a safe and tolerable tool to investigate inflammatory response in humans and could lead to better characterization of patients with chronic inflammatory disease2 .
1. Kitz R, Rose MA, Borgmann A, Schubert R, Zielen S. Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects.
J Endotoxin Res. 2006;12(6):367-74.
2. Kitz R, Rose MA, Placzek K, Schulze J, Zielen S, Schubert R. LPS inhalation challenge: a new tool to characterize the inflammatory response in humans.
Med Microbiol Immunol. 2008 Mar;197(1):13-9. Download