This study was conducted to evaluate the CT characteristics to measure the pulmonary vessel volume. Our current findings can be twofold. The fibrotic score of MDCT was significantly correlated with DLCO and PVV scores, but not with FVC. DLCO was significantly correlated with the PVV score but did not reveal the parallel trend with FVC.
In previous studies, the extent of fibrosis in MDCT was correlated with DLCO and FVC.[12, 16] This discrepancy with our results could be explained in two aspects. First, the study population of previous studies and that of our study did not greatly differ in FVC. It may lead to an insignificant association between FVC and the extent of lung fibrosis. On the contrary, the DLCO was remarkably reduced in our study. It has been observed that the lung volume and DLCO would not always change parallelly in IPF.[17, 18] A proportion of patients IPF had preserved FVC but remarkable DLCO deficiency. Meanwhile, DLCO could decline earlier and more seriously than FVC in patients with IPF. Traditionally, FVC decline was used as the primary end-point in previous clinical trials,[19–21] and recent studies showed that FVC alone cannot sufficiently define the severity of IPF and DLCO could provide another important aspect of physiology IPF deficiency, which could be associated with early diagnosis of fibrosis. Second, the fibrotic score measures the extent of pulmonary fibrosis but does not distinguish different fibrotic patterns. In Fraser et al. and Wells et al.’s studies, the extent of fibrosis more significantly correlated with DLCO than FVC.[12, 23] These findings could reflect the fact that the influence of fibrosis on lung function is complex in IPF. The extent of fibrosis may have different impacts on FVC based on disease severity. However, it also affected the DLCO more profoundly.
Jacob et al. reported that PVV was significantly correlated with fibrotic score and DLCO using both CALIPER software and visual fibrotic score, which is concordant with our results. However, in our study, patients with moderate and severe emphysema were excluded. Furthermore, the diagnosis of all patients included in this study was confirmed by MDD to further decrease the heterogeneity of our population.
The cause of the correlation between PVV and the fibrotic score remains unclear. Jacob et al. suggested that the high intrathoracic pressure generated by non-compliant fibrotic lung dilates the pulmonary vasculature, which would cause the high PVV in the fibrotic lung. Contrary to Jacob et al.’s studies, neither PVV nor fibrotic score was correlated to FVC in our study. FVC negatively reflects lung compliance in IPF. Despite the irrelevance to FVC, the correlation of PVV to fibrotic score remains robust in our study. Another possible explanation may be the change of pulmonary vasculature concurrent with the extent of fibrosis.
The PA trunk diameter was believed to indirectly reflect the pulmonary arterial pressure (PAP). In our study, we found that the PA trunk diameter was significantly correlated with PVV (r = −0.47, p = 0.006) but not with the fibrotic score (r = 0.19, p = 0.24). These findings were concordant to that of the previous studies. Jacob et al.’s study also showed the correlation of PVV with the right ventricular systolic pressure measured by echocardiography. Fisher et al.’s study using the right heart catheter to measure PAP also showed that the extent of fibrosis was not associated with PAP in interstitial lung disease. Although the pulmonary vasculature changes in IPF are still not fully illustrated, a recent study indicated that the pathogenetic process of pulmonary fibrosis may also be involved in vasculature changes. Another study by Jacob et al. also reported that higher PVV was related to increased fibrosis and higher mortality. The PVV may be an important radiological marker for interstitial pneumonitis and needs further studies to verify its significance on IPF.
In our study, FVC is significantly correlated to CT lung volume. Since the IPF is primarily the disease of elderly people. The lung function test may be too laborious to some elderly, especially for those with cognitive deficiciency.[28, 29] For patients with IPF who have difficulty performing lung function tests, the measurement of CT lung volume may be a possible surrogate to evaluate the lung mechanics. As the FVC decline was used as the physiological marker for disease progression and prognosis prediction, reduced CT lung volume may serve as the quantitative image marker for the same purpose.
This study has some limitations. First, the population size is small. Most included patients did not have reduced FVC, although patients with evident emphysema and had MDD for every patient were excluded to enhance the diagnostic homogeneity. Considering the disease heterogeneity of IPF, our study may only represent a specific proportion of the IPF population (especially for those with preserved FVC), and the result may not be applied to all patients with IPF. Second, the fibrotic score measurement is a semi-quantitative method using the average percentage of fibrosis in six levels on chest CT to represent the whole lung fibrotic condition. Despite its high reproducibility among well-trained readers (both in our study and previous studies), there is a limitation in using a few CT slices to represent the whole lung fibrotic condition. Third, regarding the pulmonary vascular volume, there is still potential to capture the misclassified reticular pattern in the PVV in patients with extensive fibrosis. Fourth, this study did not obtain information on cardiac echography or right heart catheterisation. Therefore, an association of PA pressure, PA trunk diameter and pulmonary vascularity could not be further illustrated. Finally, because the lung function parameter is expressed by the percentile of expected value already considering the age, gender, body height and body weight, a multivariable analysis of the basic characteristics was not performed. Furthermore, CT parameters including fibrotic score, PVV, PA diameter and CT lung volume were correlated to each other. Considering the problems of collinearity, we could not perform the multivariable analysis of CT parameters.