Health & Environmental Research Online (HERO)


Print Feedback Export to File
2614524 
Journal Article 
Abstract 
Modeling of house dust mite-induced chronic airway eosinophilia 
Colangelo, M; Llop-Guevara, A; Fattouh, R; Walker, TD; Goncharova, S; Lovric, M; Jordana, M 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2806 
English 
WOS:000208771001718 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
RATIONALE: Allergic asthma is a complex disease that develops as a consequence of an aberrant immune response to aeroallergen exposure. Importantly, knowledge on the dynamics and evolution of the disease has progressed largely from qualitative principles. We surmise that enhanced understanding may be achieved through the incorporation of mathematical approaches. Previously, we have demonstrated the evolution of immune-inflammatory responses in mice exposed to a wide range of house dust mite (HDM) concentrations for up to 20 weeks and showed that the relationship between allergen exposure and airway inflammation is nonlinear. In addition, the data showed that the relationship between exposure and airway eosinophilia follows a bell shape-like curve. While the extent of the response at early (increasing) responses appears to be dependent on the dose and length of exposure, later (decreasing) responses converge to similar levels. This observation presupposes a dynamic behaviour with the implication that the evolution of the eosinophilic response may be influenced by other factors. Given that this data was modeled empirically, such factors were not previously taken into consideration.

METHODS: To characterize the dynamics of the eosinophil changes in the airway, we developed a mechanistic mathematical model to investigate the evolution of the eosinophilic response to continuous allergen exposure. In order to do so, we considered known biological observations combined with mathematical assumptions. With the understanding that eosinophil trafficking between compartments determines the response in the airway, the model considers a simplified system in which eosinophils are considered in three compartments: the bone marrow, blood and lung. The number of cells within each compartment varies according to rates corresponding to processes of eosinophil production, migration and moderation with respect to HDM concentration and time.

RESULTS: The model shows that eosinophil dynamics can be primarily attributed to the ratio of positive and negative processes, identifying eosinophil production and moderation (death and survival) as having a relative importance in the evolution of the eosinophilic response. In sharp contrast, migration of eosinophils elicited an apparently small influence. Interestingly, while eosinophil production and survival exhibit dose-dependent patterns, eosinophil death remains consistent, suggesting that while eosinophil regulation is present throughout the evolution of the response, fluctuations are governed by the increase and decrease of production and survival factors.

CONCLUSION: This synergistic approach using both immunological data and mathematical analysis provides a mechanistic description of the dynamics of airway eosinophilia and provides insight into areas that may be targeted for future experimentation. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010