Functional imaging of airway narrowing

The report will focus on studies that illustrate how high resolution computed tomography can be used to provide new insights into airway and lung function, that cannot be obtained with any other methodology in humans or animal models. In one series of experiments, we have clearly demonstrated that even large cartilaginous airways are capable of complete closure in vivo. These unequivocal in vivo results invalidate the ubiquitous concept that there is a limit to airway narrowing in normal subjects. In another series of experiments, we have investigated potential reasons why asthmatic subjects might show airway constriction following deep inspiration instead of the normal dilation. Experimental results show that a constrictor response to deep inspiration can be generated in normal airways simply by minimizing tidal stresses. The absence of these normal rhythmic stresses alters the smooth muscle throughout the airway tree, such that subsequent large stresses lead to a further constriction. These results also offer a possible mechanism by which the response to deep inspiration is altered in asthmatic subjects. By allowing accurate measurement of the size of individual airways, computed tomography with modern commercially available scanners thus provides a unique opportunity to evaluate specific hypotheses regarding mechanisms underlying lung disease.