In an issue of CHEST (September 2020), Karakioulaki et al1 reinforced mounting evidence for the presence of regionally heterogeneous airway abnormalities in patients with asthma by showing histopathologic airway differences across lung lobes on endobronchial biopsy. At the lobar level, airway smooth muscle cell mass and the distance between the basement membrane and airway smooth muscle were significantly different across lobes. Airway smooth muscle cell mass was greater in lower lobes compared with upper lobes, and, although specific interlobar differences were not measured, the right upper lobe notably exhibited the least amount of airway smooth muscle mass.
Ventilation heterogeneity, which is a consequence of heterogeneous airway remodeling, may be noninvasively visualized and measured by using hyperpolarized noble gas MRI; airway morphology can be directly measured by using CT imaging. We previously reported lobar differences in MRI ventilation abnormalities in 60 patients with severe asthma2; in agreement with the findings of Karakioulaki et al,1 the middle and both lower lobes exhibited significantly greater MRI ventilation abnormalities (quantified as the ventilation defect percent [VDP]) compared with the upper lobes, and this was related to “missing” airways on CT imaging at the subsegmental and sub-subsegmental levels (generations 4-5). To illustrate this pattern, Figure 1 shows MRI ventilation co-registered with CT imaging alongside lobar MRI VDP and CT airway wall area percent measurements in a patient with severe asthma. The three-dimensional MRI-CT models are shown at oblique angles to highlight structure-function abnormalities in the middle, right lower, and left lower lobes, while the upper lobes are well ventilated.
MRI ventilation abnormalities in asthma are often spatially related to segmental airways with thickened walls on CT imaging.3 Although the underlying histopathologic airway alterations that drive MRI ventilation defects in asthma have not yet been directly evaluated, CT airway wall thickness has been shown to be related to airway epithelial thickness on endobronchial biopsy but not airway smooth muscle mass.4 We suspect that the relative contributions of different airway wall components to airway remodeling and abnormal ventilation will be heterogeneous within and between patients with asthma. The histopathologic findings of Karakioulaki et al1 and previous MRI results2,3 provide further evidence that the location of airway sampling, either on biopsy or quantitative imaging, requires careful consideration and interpretation. Moving forward, paired MRI-CT imaging can prospectively guide patient-specific bronchoscopy to better understand regional asthma heterogeneity or bronchoscopic treatments such as bronchial thermoplasty,5 with the ultimate goal of precision medicine.