In this study, with the aid of advanced QCT imaging analysis, we have investigated alterations of the airway structure and lung function at multiscale levels in subjects exposed to cement dust. Most similar studies (1-5, 8, 9) included patients with pulmonary diseases such as COPD and asthma, whereas for an objective comparison, this study excluded patients with pneumonia, asthma, and COPD to minimize confounding effects due to the pulmonary diseases. We also employed a robust statistical method of propensity score matching to control demographic confounders such as age, sex, height, smoking history, and pack-years. It has been known that imaging protocols between different centers are sensitive when estimating density-based imaging metrics such as Emph%, and fSAD% (22), whereas they are less sensitive on airway size parameters (20). Therefore, we employed a fraction threshold method to compute the Emph% and fSAD%.
With sensitive QCT imaging metrics, we demonstrated that the airway structures of DE subjects had different features from those of NDE subjects. The DE subjects are characterized by phenotypes of airway narrowing (Dh) at lower-lobes, wall thickening (WT) at all segmental airways, and alteration of branching structure (θ) at central airways. These findings were similarly observed in a previous study where individuals with occupational exposure had an increased airway wall thickness (9). In the meantime, a multicenter study of former and current smokers using the multi-ethnic study of atherosclerosis (MESA) COPD data reveals that COPD subjects caused by mainly smoking have thinner airway walls (23). The subjects in this study could be also progressed into COPD later, but these subjects exposed by cement dusts have thickened airway walls. A previous study has reported that exposure to cement dust leads to an increase in airway inflammation (24). Thus, the distinguished phenotypes on airway walls are likely to indicate different airway pathophysiology.
A recent asthma study by Shim et al. (25) using severe asthma research program (SARP) data has demonstrated an association of airway lumen change between TLC and FRC with a corticosteroid treatment, but there were no investigations of wall thickness and branching angle changes between TLC and FRC. In this study, we computed strains for airway hydraulic diameter, wall thickness, and branching angle. To our best knowledge, this is the first effort of estimating strains at bronchial levels between TLC and FRC. As a result, the DE subjects were found to have the increased stiffness of wall thickness (εWT) and bifurcation angle (εθ) which could be affected by lung fibrosis and atelectasis, possibly due to the airway inflammation. In particular, the stiffened airways were likely to affect the prevention of airway deformation from FRC to TLC, sustaining the airway skeletal structure at FRC.
Regarding parenchymal functional variables (Table 4), lung volume at TLC, lung volume at FRC, IC, and Jacobian in DE subjects were smaller than NDE subjects. The decreased IC and Jacobian in DE subjects also could indicate a reduction of lung deformation. Especially, the reduction of Jacobian was found to be significantly correlated with eq at RMB (Spearman test R=0.416, P<0.005). Based upon our analysis, we presume that the significantly reduced lung volume at TLC was caused by a reduced volume change (Jacobian). This is also possibly correlated with an increased stiffness of airways estimated by eWT and eq (Table 3 and Fig 6). In this study, fSAD% of DE subjects was similar with NDE subject, and Emph% of DE subjects was even lower than NDE subjects (Table 4). This is possibly due to the subgrouping by normal lung function, and also indicates that structural alterations of segmental airways begin earlier than parenchymal functional alterations.
Compared with lung functional metrics, airway structural variables provided very clear differences between the DE and NDE subjects. This implies that dust exposure due to cements was significantly associated with bronchial alterations in segmental scales rather than in parenchymal levels. As the size of cement dust ranges from 0.5 to 5 mm (16), cement particles may be deposited in segmental airways (24, 26, 27). These features are different from the characteristics of cigarette smoke particles. Sahu et al. (28) demonstrated that the deposition rate of cigarette smoke particles was greater in parenchymal regions than in segmental regions due to the small size of the particles (ranging from 0.01 to 1 mm). A previous study found that smokers with normal spirometry were more susceptible to parenchymal alteration associated with the emphysema score (29, 30). Whether the structural alterations observed here progress to parenchymal levels, leading to severe air-trapping and emphysema, has yet to be confirmed with a longitudinal study.
This study has several limitations. It was retrospectively designed by utilizing CT images collected at two respective sites. Thus, the findings obtained here were possibly influenced by intersite variability, such as scanner difference. However, as shown in Table 1, the two centers used the same scanner make (Siemens), same inspiratory maneuver (TLC), same expiratory maneuver (FRC), and similar reconstruction algorithms (B30f from KNUH and B35f from CNUH), so consistent regional attenuation, airway diameter, and wall thickness between the two groups are expected (31, 32). In addition, the percent emphysema and percent fSAD were derived from the method using a fraction-threshold (10) that is a density variation-free method. Therefore, these results were not significantly influenced by scanner differences. In the previous study (20, 33), we already confirmed that different scanner had little confounding effect for QCT analysis with data derived from different sites. Furthermore, dust-exposed subjects could suffer from several pulmonary diseases such as interstitial lung disease and fibrosis which were not indicated by FEV1 and FVC. Therefore, it was better to include DLCO for the criterion when choosing subjects with normal lung function. Unfortunately, DLCO was not collected in this project, but we excluded any noticeable parenchymal diseases such as fibrosis, asthma, and pneumonia, so we believe that the current features in cement dust exposed subjects remained the same.