Grant: Project Grant

Two million people suffer from uncontrolled asthma in Canada. Asthma is a respiratory disease characterized by breathing difficulty caused by excessive airway narrowing. This narrowing is the result of contraction of the smooth muscle (SM) in the airway wall. While many asthmatics have increased airway SM mass, which may explain excessive airway narrowing, others do not. Thus, these latter cases may suffer from increased contractile capacity of individual SM cells. We have shown that in the horse with heaves, an animal model of asthma, the rate at which airway SM shortens is increased whereas airway SM of horses under remission exhibits an increase in stress and stiffness. Thus, we hypothesize that different subtypes of asthma are characterized by differences in airway SM contractile properties. We propose to develop a "lab on a chip" device for measuring these contractile properties from SM cells acquired by biopsy from people with asthma. Goal: To identify asthma subtypes by measuring the rate of shortening and the contractile force of airway SM from biopsies of human asthmatics and controls. Approach: Airway SM cells from biopsies will be isolated and injected into a device that we will develop from two layers of silicone, each containing a network of micro-channels. Cells will flow into separate lanes and get sucked to the floor of the lanes, which is made up of micro-pillars of known stiffness with perpendicular channels, attached to a low-pressure source, in between them. The immobilized cells will be exposed to contractile or relaxing solutions and bending of the micropillars by the contracting cells will allow measurement of the contractile force, while a sudden release of the cells will allow measurement of the rate of shortening. Significance: This study will enable differential diagnoses of asthma subtypes based on airway SM contractility, directly contributing to more effective, personalized treatments.