Monday, February 13, 2017

Heterogeneity of airway wall dimensions in humans: a critical determinant of lung function in asthmatics and non-asthmatics

Airway remodeling is a cardinal feature of diseases such as asthma. Previous measurements and modeling of the airways of non-asthmatics vs. asthmatics have shown that increased airway smooth muscle contributes substantially to remodeling and the resultant narrowing of the airway lumen. However, the assumption in models based on lung morphometry is that narrowing occurs proportionately, i.e. homogenously along the branches of the bronchial tree. In this elegant modeling paper based on measurements of airway lumens from asthmatics vs. non-asthmatics, Pascoe et al. demonstrate for the first time that there is profound heterogeneity in the extent of remodeling along the different branches of the bronchial tree, with small airways contributing particularly to such heterogeneity. The predicted physiological importance of this heterogeneity in airwaywall dimensions of non-asthmatics and asthmatics lies in their contribution to airway hyperresponsiveness (the model predicting a leftward shift in the likely dose response to bronchoconstrictor agonist). Here, closure of small airways is predicted, as is known to occur in obstructive airway disease. However, what is interesting is that a disproportionate or greater heterogeneity in asthmatic airways does not necessarily predict AHR, but it is the increase in airway wall dimensions that does. The appeal of such elegant modeling studies in human lungs of asthmatics vs. non-asthmatics lies in emphasizing the need for more mechanistic studies on remodeling, particularly of the small airways that contribute to premature closure and obstructive disease, and importantly in the need for improved imaging techniques of the small airways, particularly under standardized conditions that would allow for accurate and sensitive assessment of the extent of airway remodeling, its changes with time (e.g. in aging or asthma in the elderly) or responsiveness to therapies.

Y.S. Prakash
Deputy Editor

Link to the manuscript ; Pascone, CD et al...

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