Airway remodeling describes structural changes that in the asthmatic airway collectively result in thickening of the airway wall. CT imaging of the airways is being developed as a technique to study airway remodeling in vivo. Multiple studies, have documented increased airway WT in asthma using CT. Most of these studies employed manual tracing methods, using either manual or digital measurement of airway dimensions. These previous studies using manual tracing methods have demonstrated significant differences in comparing asthma patients to healthy subjects, though these differences may be related to selection bias. Kasa-hara et al found that the radiographic measurements of WT and WA were increased in asthma patients, correlated with LR, and inversely related to FEV1. A pediatric study found similar, although less robust, results. To improve objectivity, reproducibility, and efficiency, automated airway segmentation and analysis methods have been implemented. However, automated assessments previously have been restricted to those airways that are nearly round in transaxial images, so that the long axis is roughly perpendicular to the scan plane. Consequently, quantitative measurements were obtained only on (nearly) round airways in a limited number of slices, which may lead to potential selection bias as our data demonstrate significant regional heterogeneity in segmental airway remodeling. The automated technique we used eliminated selection bias by segmenting, labeling, and measuring all of the proximal airways, and allowing comparison of those airways that may have been excluded using previous methods.
In this study, we used an automated, quantitative software program to analyze and measure the differences in airway WT between patients with severe asthma and those with milder disease. We found that when using MDCT scan indexes of airway WT that account for TA, specifically WT% and WA%, patients with severe asthma have on average slightly more thickened airway walls compared to those with mild-to-moderate asthma and healthy subjects. Interestingly, there was no significant difference when comparing airway WT% or WA% in patients with mild-to-moderate asthma with those in healthy subjects. Previous studies, normalized airway measurements to the total airway diameter/area or body surface area. Our data demonstrate that there is substantial variability in the measurement of airway diameter and lumen between airways in the same subject and between subjects, and that this must be taken into consideration when averaging data. Our measurements were normalized for segmental total thickness or TA, which accounts for the interairway variability.
Furthermore, we found that the MDCT scan indexes WT% and WA% correlated with physiologic measures of airflow obstruction across subjects. Similarly, Kasahara et al also found that WT, WA, and LR were all inversely correlated with post-bronchodilator therapy FEV1. Increased segmental airway thickness may correlate with more distal, small airway narrow-ing. Gono et al compared expiratory and inspiratory lung density measurements to assess airtrapping as a measure of small airways disease. Asthmatics with irreversible airflow obstruction had significantly higher expiratory/inspiratory ratios than asthma patients whose expiratory flows normalized after bron-chodilation. Hasegawa et al, in a study using threedimensional measurements of airway dimensions in COPD patients, focused their analysis on two bronchi (the RUL and right lower lobe) and found statistically significant correlations among LA, WA%, and FEV1 percent predicted. They also found a stronger correlation when distal smaller airways (up to sixth generation) were analyzed. These findings suggest that airway remodeling in more proximal airways reflects similar changes occurring in more distal airways, resulting in measurable airflow limitation and airtrapping.
A current limitation of MDCT scan measures of airway thickness is the inability to be more specific about which component of the airway has truly changed. In our study, we are unable to discern whether the MDCT scan findings of increased WT% and WA% in patients with severe asthma truly reflect increases in epithelial and LR changes or some other feature of airway remodeling such as increased smooth muscle mass. This particular aspect of airway remodeling has not been well characterized due to the limited sample of smooth muscle available with an endobronchial approach. Future longitudinal studies are needed to evaluate temporal changes in airway WT within individual patients and to evaluate the effects of different treatments.
There are limitations to our ability to measure airway remodeling and accurately obtain airway biopsy specimens from the same segment measured by MDCT scan. The biopsy sites were obtained from the upper lobes only; therefore, we are not able to generalize our remodeling measures to other lung segments. Accurate histologic measurement of the epithelial and LR layers requires that the biopsy specimens have an intact epithelium; therefore, not all biopsy specimens were included in our analysis.
The natural history of airway remodeling in asthma patients, its rate of progression, and its response to treatment are questions that remain unanswered. Noninvasive measures of airway remodeling using MDCT scanning would allow us to longitudinally monitor the effects of various stimuli and treatments on remodeling. Eventually, this technique may help to identify individuals with asthma in whom severe disease is likely to develop and who may benefit from early targeted, aggressive therapy.
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