4 DISCUSSION
Lung densitometry, that is, lung density measurement, is a quantitative CT measurement method capable of measuring structural abnormalities in the lung based on the characteristics of lung tissue that variably attenuate X-rays. Parenchymal abnormalities can typically result in reduced attenuation in emphysema or cystic lung disease or in increased attenuation, as in pulmonary fibrosis6. The presence of pathologic air trapping in the expiratory phase on CT scan has been defined as a parameter for detecting diseases in small airways7. In particular, in patients with BO, radiologic detection of bronchial dilatation infrequently precedes the clinical diagnosis of disease; air flow limitation in expiratory CT scans has been suggested as the most appropriate indicator for early diagnosis compared to PFTs and transbronchial biopsy8,9.
Previous studies performed quantitative CT analysis to detect air trapping in adult patients with COPD10-12, asthma13, and lung transplantation14. Parameters including density mapping, emphysema or air trapping index, MLD, and 15th percentile density index were analyzed. To the best of our knowledge, there have only been a few quantitative densitometry studies in pediatric patients15-17.
Our results suggest the possibility of quantitative pulmonary function evaluation through CT in pediatric BO patients, as in 19 (23.5%) out of 81 patients, who were unable to complete spirometry measurement. In our experience, in children aged 4–5, who are younger than the age at which spirometry can be performed, the cooperation of 3D CT to control inspiration and expiration was sufficiently possible. LAA from both -850 and -900 HU thresholds showed a statistically significant correlation with specific airway resistance sRaw in multivariate analysis, indicating high OR and high AUC values for BO diagnosis. In previous studies in adult patients, the attenuation threshold range from -856 to -950 HU has been shown to be the most applicable for identifying pathologic air trapping 10,18-22.
According to previous studies regarding lung development, the lung continuously grows in proportion to body size after birth, but the formation of new alveoli stops around the ages of 2–823,24. During the period of formation of new alveoli, lung density is relatively constant. However, the lung density is expected to decrease according to the growth of the lung, following the increased alveoli airspace volume. Robert et al. showed that the lung structure of subjects with larger lungs differs from those with smaller lungs and that larger lungs have a thinner septum and lower parenchymal density as the air volume in the alveoli increases 25. Interestingly, our study showed that the densitometry expiratory threshold of airflow limitation is similar to or slightly lower than that of adults. This finding is supported by a previous study, where the overall MLD of a group with an average age of 2 was similar to that of adults 26. It is also consistent with Christian et al.’s suggested -925 to -950 HU threshold in a recent study, which included adolescents with HIV BO patients with mean ages similar to those in our study 15.
The methods frequently used for quantitative analysis of air trapping using CT include (a) the difference or the ratio of the expiratory/inspiratory MLD and (b) the measurement of the percentage of the lung area showing below the threshold HU during exhalation. Pathologic air trapping was defined as a voxel difference of less than 80 to 110 HU between expiration and inspiration within segmented lung parenchyma 14,27,28. In our study, the MLDD cut-off of BO diagnosis between expiration and inspiration was 109.0, which is consistent with previous studies. In multivariate linear regression analysis, the difference (MLDD) or the ratio of the expiratory/inspiratory MLD (E/I MLD) showed a strong correlation with FEV1, and the -850 to -950 HU threshold method showed a significant correlation with sRaw (Table 2). This indicates that each LDI and PFT parameter can be independently specific to reflect different anatomical areas that are responsible for pathological lung function.
Previous studies on the E/I ratio of MLD have shown a stronger correlation with the spirometric airflow limitation parameters than the density threshold-based method of air trapping 22,29. E/I MLD showed a strong correlation with FEV1, FEV1/FVC, FEF25-75, and FRC/TLC ratios as well as markers with respiratory morbidities14,29. In our study, in contrast, expiratory -900 HU (E900) showed the highest AUC in the ROC analysis for BO diagnosis compared to other LDIs; this was a single factor that consistently showed a significant strong correlation with the PFT parameter in various correlation analyses.
Our study has multiple strengths. This is a study of lung densitometry in pediatric BO patients, and it extensively investigated the correlation between various densitometry and pulmonary function parameters. We suggested an additional role of quantitative CT in evaluating pulmonary function in difficult pediatric BO patients with poor PFT cooperation and a low reliability of test results. The main limitation of our study is that it is a retrospective study using a small sample size of patients. Since young children have varying lung volumes and structures with age, the patients included in our study are likely heterogeneous populations with varying lung densities. Further study is needed to determine whether a fixed lung density threshold can be applied to pediatric BO patients of various ages.
In conclusion, quantification LDIs obtained through chest CT scans have a significant correlation with conventional PFTs. The ratio of the E/I MLD and the LAA below the threshold -900 HU complements the diagnosis of pediatric BO patients by providing additional quantitative indications of progressive expiratory air flow limitation.