In this retrospective study, we compared the clinical prognosis of patients with AE-CPFE with that of patients with AE-IPF. Our results demonstrated that the prognosis of AE-CPFE was significantly better than that of AE-IPF.
CPFE is characterized by emphysema in the upper lung and pulmonary fibrosis in the lower lung on CT images. Usual interstitial pneumonia and nonspecific interstitial pneumonia are typically observed in patients with CPF. However, we only compared cases of IPF with cases of CPFE with findings of fibrosis concomitant with UIP on thin-slice chest CT images.
In the present study, patients with AE-CPFE had a significantly better prognosis and a higher survival rate than did patients with AE-IPF. A recent study demonstrated that the survival rate of AE-IPF was 66% within 1 month and 41% within 3 months [12]. This finding was consistent with the findings of our study, which showed a survival rate of 61.0% within 30 days and 43.9% within 90 days in patients with AE-IPF.
Previous studies have reported that a low %FVC and percentage of predicted carbon monoxide diffusing capacity in lung function tests and high KL-6 and lactate dehydrogenase serum levels before AE are risk factors that contribute to a poor prognosis in patients with AE-IPF [13, 14]. The present results also demonstrated that the %FVC was significantly lower and the levels of KL-6 were significantly higher in the IPF group than in the CPFE group before an AE.
There were no significant differences in the P/F ratio, GAP score, and use of supplemental oxygen between the two groups before AE. This finding suggested that the respiratory status of the patients in the two groups was similar before AE. Thus, the disease severity before AE did not differ between the two groups.
Yoon et al. [15] reported that IPF was concomitant with emphysema in some lung fields in 42% of their patients, and this finding was based on high-resolution CT. In the present study, patients with CPFE had an LAA score ≥7, which implied that the lung field with emphysema was larger and the lung field with fibrosis was smaller in the CPFE group than the lung field with emphysema and the lung field with fibrosis in the IPF group.
The KL-6 level at the time of AE was significantly higher in patients with IPF than that in patients with CPFE. This finding suggests that the lung injury in patients with IPF was more severe than that in patients with CPFE. The area of diffuse alveolar damage, which is a histopathological hallmark of AE-IPF, may be smaller in AE-CPFE than that in AE-IPF because of emphysema. We propose that the difference in the composition of fibrosis in the lung fields between the two groups may have led to the difference in prognosis between patients with AE-IPF and patients with AE-CPFE.
One report [11] indicated that the mortality rate of patients with AE-IPF was higher for individuals with the diffuse ground-glass pattern than for those with the multifocal pattern or peripheral pattern on CT images. The present study revealed that there were no significant differences in the distribution of the CT pattern classifications between the two groups. Moreover, the prognosis of the CPFE group was good, even in patients with the diffuse pattern type. This finding suggests that the pathogenic mechanism of AE-CPFE may differ from that of AE-IPF, and diffuse alveolar damage may not exist in AE-CPFE.
Another possibility is that the pathogenesis of emphysema may antagonize the pathogenesis of ongoing diffuse alveolar damage. Wang et al. [16] demonstrated that urokinase plasminogen activator (uPA) and the urokinase plasminogen activator receptor (uPAR) were overexpressed in alveolar macrophages and in the bronchial epithelium in patients with chronic obstructive pulmonary disease. Moreover, another study [17] demonstrated that lung fibrin clearance was accelerated in a lung-specific inducible uPA-expressing transgenic mouse line. This transgenic mouse line was protected from fibrosis and mortality associated with bleomycin-induced lung injury. Furthermore, the risk of radiation pneumonitis was lower in patients with severe emphysema, such as the patients in our study, than that in patients with no underlying lung disease [18]. However, this is a hypothesis, and we intend to test this hypothesis in future studies.
Our study had several limitations. First, it consisted of a single-center retrospective study that included a small sample of patients. Some patients were transferred to our hospital after the onset of the AE; thus, their data before the AE were insufficient. Second, only one IPF patient had undergone a surgical lung biopsy, and patients with UIP on HRCT may not necessarily exhibit UIP in pathological examination. However, the patients’ clinical characteristics, physiological impairments, and clinical courses were entirely compatible with IPF. Third, only some patients underwent bronchoscopy, and the bronchoalveolar lavage fluid could not be evaluated at the time of the AE. Therefore, the pathogenic mechanisms underlying the differences between AE-CPFE and AE-IPF should be analyzed in future research.