Asthma is a disease of the airways, which is characterized by airway hyperreactivity (AHR). Airway hyperreactivity causes excessive airway constriction and closure in the lung during an asthma attack. The cause of AHR is not currently understood. It is thought that AHR is the results of airway wall remodeling, or by a defect in the airway smooth muscle (ASM). The goal of this research project is to test the following hypothesis.

Hypothesis 1: The ASM-airway system can transition to a more reactive state via long-term prohibition of maximal airway dilation, and the cause is not limited to airway wall remodeling or chronic inflammation.
Hypothesis 2: Airway wall thickening has two impacts on airway reactivity. First thickening of the airway wall enhances reactivity by altering the load which the ASM must constrict against, regardless of the ASM becoming thicker. Secondly, thickening of the ASM layer of the airway wall could lead to a stronger ASM that is able to generate more tension, and hence enhance reactivity.

To do this I will carry out 2 experimental studies and 1 computational study. The first experimental study involves making measurements of lung resistance and reactivity in subjects with spinal cord injury (SCI). They have been shown to have AHR in the absence of airway wall remodeling. This will allow us to determine if inhibition of stretch leads to enhanced airway reactivity in vivo. We will also test this hypothesis on the in vitro levels using airway of excised calf lungs. In the computational study a model developed by Lambert will be modified to determine if airway wall remodeling is the primary cause of AHR and if the thicker ASM of asthmatics must be stronger.

Human Lung (top left) from Tawhai et al. 2000