Grant: CIHR Fellowship

The muscle surrounding the airways is the final common pathway involved in the airway narrowing that characterizes all types of asthma. Recently, bronchial thermoplasty, an intervention that partially removes the muscle from the airways, was shown to cause long-term improvements in the symptoms of asthmatic patients. This intervention is limited by its invasive nature, numerous side effects, and by the fact that it targets only larger airways (>3 mm) that are accessible with a bronchoscope. However, the result of these clinical trials clearly demonstrate that less invasive therapy capable of targeting the airway muscle of large and small airways would be an effective therapy for asthma and could reduce or eradicate the symptoms of this disease. Our group has recently demonstrated that cyclical stretching of airway muscle reduces its force. This implies that the cyclical stretching of the muscle, which is seen in normal breathing and periodic deep inspiration, is protective against excessive airway narrowing. Our preliminary results suggest that the muscle becomes stiffer when repeatedly stimulated to contract. We propose that the increased muscle stiffness, caused by chemicals released during allergic inflammatory reactions in the airways, reduces the cyclical stretching induced by normal breathing and periodic deep inspiration. This reduced stretching, in turn, increases muscle force and contributes to the exaggerated airway lumen narrowing observed in asthmatics. A better understanding of the mechanisms regulating the stiffness of the airway muscle may shed light on the origin of the exaggerated bronchospasm in asthmatics. Ultimately, these results may lead to the identification of a new method of treatment for asthma and an alternative option for the unmet need of patients unresponsive to current treatments.