Mathematical modeling of nitric oxide and mucus dynamics in the human lungs, using a phenomenological approach, to provide new insights into asthma and cystic fibrosis.

• Main Author: Karamaoun, Cyril
• Other Authors: Haut, Benoît
• Format: Doctoral Thesis
• Language: fr
• Published: Universite Libre de Bruxelles 2017
• Subjects: Sciences de l'ingénieur; Biophysique; Physiologie générale [biophysique]; Asthma; Cystic Fibrosis; Modeling; Biophysics; Nitric Oxide; Mucus
• Online Access: http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/259931

In this work, the general problematic of the transport phenomena in the lungs is addressed, with applications to lung diseases, in particular asthma and cystic fibrosis. Regarding these two major diseases, the dynamics of the nitric oxide and the mucus layer in the lungs, respectively, are of particular interest. In asthma, it has been shown that the measurement of the exhaled concentration of nitric oxide can be used as a proxy for monitoring the disease status. In cystic fibrosis, which is a disease of the mucus layer, pieces of evidence show that the water content of the mucus is linked to the severity of the symptoms of the disease. In both conditions, however, these links are far from being obvious. Regarding nitric oxide, its exhaled concentration is not straightforwardly related to its concentration in the lungs. Regarding cystic fibrosis, the link between the disease and the alterations of the mucus content and dynamics is far from being understood. From these observations, several modeling approaches have emerged to complement the clinical measurements. In this work, the dynamics of the nitric oxide and of the mucus layer in the lungs is studied from a modeling approach, following a phenomenological point of view. Regarding the nitric oxide, a new model of its dynamics in the lungs is developed. When compared to previous ones, the model presents multiple new features that allow for a better description of this dynamics, especially in the case of asthma exacerbation, characterized by the presence of mucus obstructions and bronchoconstriction. From this model, the role of nitric oxide as a general marker of the bronchi caliber is suggested, in addition to its role in the asthma monitoring. Furthermore, based on clinical measurements of the exhaled nitric oxide concentration in cystic fibrosis patients and the use of the new model, the role of the measurement of nitric oxide in the understanding and control of other lung diseases, such as cystic fibrosis, is evaluated. Regarding the dynamics of the mucus layer in the lungs, a new analysis of the control of the mucus balance in the bronchial region of the lungs is presented in this work. Our approach is based on the combination of a balance equation for the mucus in an airway and a computational tool characterizing the evaporation of the mucus in the bronchial region. We show that this approach allows for new insights into the dynamics of the bronchial mucus and, more specifically, on the mechanisms controlling the amount of mucus in an airway. The results are analyzed in order to bring interesting new perspectives for the understanding and the treatment of mucus pulmonary diseases,such as cystic fibrosis. Altogether, this work demonstrates, applied to medical pathologies, the usefulness of modeling approaches in giving a mechanistic view of the encountered problematic. === Doctorat en Sciences de l'ingénieur et technologie === info:eu-repo/semantics/nonPublished