Existence of patchiness in constricted lungs : from experiments to complex system modeling

Abstract

Understanding asthma pathophysiology can directly help researchers and physicians pinpoint mechanisms that govern airway hyperresponsiveness and effectively treat complex respiratory diseases such as asthma. The advancement in this research field has been prompted by the usage of medical imaging technology and computational modeling providing a subjectspecific, noninvasive assessment of respiratory structure and function in vivo. This thesis features several attempts to study mechanisms of bronchoconstriction and interdependence between respiratory structure and function. First, with complex system modeling of a network of airways, I investigated the effect of breathing patterns on the catastrophic closure of airways and the emergence of patchiness hypothesized to occur during an asthma attack. Second, from High-Resolution Computed Tomography (HRCT) images of the lung, the effect of longitudinal heterogeneity on resistance to airflow within central airways was studied. Lastly, the relationship between respiratory structure and function estimated from Positron Emission Tomography (PET) and HRCT images was examined. Responses of central airways to a simulated asthma attack was not able to explain the observed ventilation, thus prompting for an estimation of peripheral airway resistance to be added such that the predicted ventilation matched the ventilation observed in PET scans. Three mechanisms hypothesized to be responsible for airway hyperresponsiveness in asthma and their influences on peripheral airway response were tested in our data set. In conclusion, we successfully identified the mechanism that was directly correlated with hyperresponsiveness of peripheral airways in asthma.