Missing airways, ventilation defects and conductive airway physiology in asthma.

Extract

While airway obstruction, either by excessive luminal narrowing or mucus plugs, is recognized as a characteristic feature of various lung diseases, its measurement by physiological testing or lung imaging has been challenging. Currently, combined application of multiple imaging modalities allows for the quantification of obstructed airways and their link to ventilation defects. In asthma, computed tomography derived total airway count (TAC) and hyperpolarized gas magnetic resonance imaging derived ventilation defect percent (VDP) were shown to be interrelated [1]. In parallel, realistic models of asthma patients’ airway trees have pointed to the pivotal role of the asymmetrical distribution of compliant lung units in generating ventilation heterogeneity [2, 3]. In particular, the fact that the volumes of compliant lung units subtended by the bronchial tree are not perfectly symmetrically distributed at each bronchial bifurcation (coined here as “bronchial asymmetry”), introduces ventilatory flow asynchronies that produce positive phase III slopes. Such bronchial asymmetry was shown to be directly linked to conductive ventilation heterogeneity (Scond) as derived from phase III slope analysis of N₂ multiple breath washout (MBW) curves [3]. Even a normal lung shows some degree of bronchial asymmetry (amongst others due to the shape of the thoracic cavity imposing the physical boundaries for lung growth) and also a non zero Scond. However in asthma, bronchial asymmetry can be greatly enhanced by the superimposed effects of narrowing of bronchi subtending the compliant units. In extreme case of complete bronchial obstruction, this dramatically affects the asymmetrical distribution of the compliant units communicating with the mouth where Scond is measured. In fact, the impact of bronchial asymmetry is a likely mechanistic explanation for the observation that in asthma, Scond is a major determinant of airway hyperresponsiveness, independent of airway inflammation [4].