The most important finding of this study is that, although there is a very good correlation between CT and OCT measurements of airway wall dimensions, OCT appears to be a more sensitive method for discriminating the changes in the more distal airways of subjects with a range of expiratory airflow obstruction. OCT-based measurements of WA%, which estimates airway wall thickness (corrected for the size of the airway), in the fifth-generation airway were more sensitive to changes in subjects' lung function, as assessed by FEV1
% predicted than were CT-based measurements on the same airways. Neither OCT- nor CT-based measurements in the large (third-generation) airways were associated with FEV1
. This is not surprising because the primary site of airflow obstruction is the small peripheral airways (4
It is well known that the chronic airflow limitation seen in people with COPD is related to a combination of the loss of elastic recoil pressure due to emphysema and increased resistance in the small airways. The exact contribution of these mechanisms to COPD is believed to be under genetic control, and the ability to noninvasively phenotype individuals into those whose airflow limitation is due to airway remodeling versus emphysema is of great interest. CT scans have been proposed as an ideal method to phenotype subjects because both lung density changes due to emphysema and airway wall dimensions can be measured (7
). However, it has been noted that CT has many problems associated with airway wall measurements, and its sensitivity in predicting FEV1
is suboptimal. Nakano and colleagues originally published results that showed that FEV1
was correlated with both low attenuating areas on CT (emphysema) and WA% of the apical segmental bronchus (7
). Hasegawa and coworkers recently were unable to show this correlation between FEV1
and third-generation airways, but by tracking the airways out to the sixth generation, they were able to show a modest correlation with FEV1
). These findings make intuitive sense because it is well established that the major site of airflow limitation is in the small airways (3
). Therefore, the association between airway wall dimensions and FEV1
should be stronger in smaller airways, especially in subjects with severe airflow obstruction. Furthermore, our data show that, although there is a significant correlation with FEV1
, the slope is not sufficiently steep to detect subtle (but likely clinical relevant) changes in FEV1
. It is possible that CT is not very sensitive to differences in FEV1
because of suboptimal resolution of small airways as the limits of CT resolution are approached (10
). OCT is a new, relatively noninvasive technique for measuring airway wall dimensions. Because the resolution of OCT is between 5 and 15 μm (14
), this will provide greater spatial resolution and hence more accuracy to wall measurements of small airways.
The data from the present study show that there is a very good correlation between CT and OCT measurements of airway dimensions. Previous studies suggest that, compared with histologic measurements of small airways, which is the current gold standard, CT-based measurements tend to overestimate wall thickness and underestimate lumen area (10
). The CT measurements of Ai are larger across all airway sizes, suggesting that increased lung volume during the CT scan compared with bronchoscopy may increase the lumen area. However, the change in WA will be minimal across the breathing cycle because it is a solid structure, which makes its dimensions harder to change. The relative difference in the WA measurements is largest in the small airways and least in the large (see
online supplement). This suggests that, as the airway approaches the resolution of the CT scanner (i.e., as the pixel size of the CT image becomes larger than the airway of interest), the superior resolution of OCT becomes very important. Although newer CT airway algorithms may be able to measure airways with submillimeter resolution (21
), CT is still limited by the resolution of the CT scanner, which is approximately 0.5 mm. The current data indicate that, in all cases, OCT-based measurements of airway dimensions were smaller than those obtained on CT scans and, although we do not have histologic confirmation of the airway dimensions, we believe that OCT-based measurements of wall thickness may be more accurate in assessing remodeling changes in the small conducting airways because of the increased resolution of OCT compared with CT. This may explain why WA% values obtained on OCT were more responsive to changes in FEV1
than were those generated from CT scans. shows images of airways obtained from a subject with normal FEV1
and low FEV1
and it is obvious from the data and the image that OCT can measure the differences in airway wall thickness in these fifth-generation airways. OCT may therefore be superior to CT in assessing the “small airway” phenotype of COPD and in evaluating disease progression over time and the effects of novel drugs on small airway remodeling of COPD.
The other major advantage of OCT is that there is no radiation exposure associated with this procedure. Although the risk of radiation-related cancer is low with CT scans, there is growing concern in the public regarding safety of CT scans (11
). The use of OCT eliminates this risk. The disadvantage, however, is that OCT requires bronchoscopy.
There are limitations to the current study. First, although the distribution of FEV1 values was heterogeneous, we only had two subjects whose FEV1 was below 50% of predicted. Thus, the accuracy of detecting remodeling changes in the airways with OCT in patients with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 3 and 4 disease requires further studies. Second, as the subjects in this study underwent only one bronchoscopic session, we could not evaluate the reproducibility of OCT measurements over time. However, it is important to further evaluate the use of OCT in combination with genomic or protein biomarker studies that require a bronchoscopic procedure to retrieve bronchial cells and bronchoalveolar lavage fluid to improve our understanding of the pathogenesis of airway diseases such as COPD and asthma as well as the effect of therapeutic intervention, especially novel treatments,
In summary, the present study suggests that OCT is a more sensitive tool in detecting airway wall remodeling in current and former smokers compared with CT scans, which raises the possibility that OCT could be used to study airway changes in vivo in patients with COPD and assess therapeutic potential of novel airway therapies.