Peripheral lung mechanics in asthma: exploring the outer limits

Asthma is a disease characterized by airways hyperresponsiveness (AHR), which is traditionally thought to involve the large, central airways. However, there is increasing evidence of the importance of peripheral airway involvement in asthma as well. Our group has developed particular expertise in measuring peripheral lung mechanics in both humans and mice. This presentation will review data on lung mechanics in subjects with asthma obtained by both classical means and uniquely through the wedged bronchoscope, as well as relevant experiments in mice. Our findings reveal that the lung periphery is hyperresponsive to stimuli in asthmatic subjects, with evidence of airway closure. We also show that the overall impedance of the lung is determined by a combination of peripheral airway narrowing and central airway shunting that occurs in both normal and asthmatic subjects. Experiments in mice have revealed the importance of airway closure in contributing to the phenomenon of AHR. Based on the effects of fibrin on lung mechanics, fibrin may contribute to airway closure via inactivation of surfactant. Another mechanism contributing to AHR is the heterogeneity of airway narrowing. We have explored this in humans by combining the forced oscillation technique with computerized tomography imaging of the lung, and demonstrated that heterogeneity is common to both normal and asthmatic subjects. Further experiments are ongoing and planned in both mice and humans to elucidate the role of fibrin, surfactant and heterogeneous airway narrowing and closure in contributing to AHR in asthma.