The present study retrospectively compared the clinical and follow-up data between 259 survivors and 80 decedents with fibrosing ILD. In this study, we demonstrated that smoking history, age, CEA, CYFRA21-1 and DLCO% predicted could predict the survival of fibrosing ILD patients independently. A new predictive scoring system namely ACDS (age [A], CEA and CYFRA21-1 [C], DLCO% predicted [D], and smoking history [S]) was proposed. Importantly, we found that scoring system level was closely associated with the prognosis of fibrosing ILD patients. Furthermore, the increased age, CEA and CYFRA21-1 were positively associated with the severity of patients with fibrosing ILD.
Fibrosing ILD had similar biological and clinical behaviours which was characterised by progressive deterioration in lung function, progressive deterioration in lung function and high mortality rate(12–13). Investigating the prognostic value of markers across fibrosing ILD was of great importance to clinical evaluation and make continues to elucidate the approach to fibrosing ILD management. In the past few years, several serum markers were identified as simple and readily accessible biomarkers to predict the survival and severity of fibrosing ILD. There were researches studying tumor markers such as CEA, carbohydrate antigen 19 − 9 (CA 19 − 9) and CYFRA21-1 that might reflect the severity and prognosis of fibrosing ILD(14–16). One retrospective study by Fahim A et al., which included 41 non-smoking patients with idiopathic pulmonary fibrosis(IPF), reported that serum CEA concentration was elevated in approximately half of patients with IPF and was correlated with disease severity(17). These results were consistent with the finding of our study of CEA as a biomarker in fibrosing ILD patients. In our study, CEA was identified as an independent prognostic factor for fibrosing ILD. CEA is a glycoprotein involved in cell adhesion and is produced by colonic epithelium. It has reported that CEA localizes in metaplastic epithelium lining honeycombed bronchioles by immunohistochemical staining. As cuboidal pneumocytes are the predominant source of epithelial renewal in severe lung damage and fibrosis, these cells are the most likely source of CEA release(18).
In this study, elevated serum levels of CYFRA21-1 were observed in decedents group with fibrosing ILD. In a study by Vercauteren et al., higher level of CYFRA 21 − 1 in BAL of IPF patients resulted in worse survival in comparison with the CYFRA 21 − 1 low counterpart (19). The expression of CYFRA21-1 in the lung has been identified in bronchiolar epithelial cells and pneumocytes. Elevation of serum CYFRA21-1 concentration might be associated with lysis or regeneration of these cells (15). Furthermore, we demonstrated that serum CEA and CYFRA21-1 were significantly correlated with decreased DLCO%predicted in this study. The severity of ILD is usually based on pulmonary function test results such as DLCO%predicted(20). Thus, serum CEA and CYFRA21-1 levels might be useful for reflecting the severity of fibrosing ILD.
A large amount of studies reported that smoking was closely associated with the onset and progress of pulmonary fibrosis(21–22). A possible explanation may be that cigarettes contain the cytotoxic, mutagenic and proinflammatory substances. According to previous reports, these substances caused cellular oxidative stress, increased epithelial cell apoptosis, and dysregulation of immune responses, which was responsible for the progress of pulmonary fibrosis(23–24). In addition, smoking affects the function of macrophages. It induced macrophage polarization to M2 phenotype that enhance the regression of inflammation and tissue remodeling(25). Therefore, smoking cessation could be a good way to slow down the development of pulmonary fibrosis in the patients with ILD.
In the past years, few models has been proposed to predict the severity and prognosis of IPF. Glasgow prognostic score (GPS) has been reported to play an important role in predicting mortality in patients with acute exacerbation of IPF(26). In our study, smoking history, age, CEA, CYFRA21-1 and DLCO% predicted were identified as independent factors for predicting the prognosis of fibrosing ILD. Moreover, based on these variables, a new predictive scoring system namely ACDS (age [A], CEA and CYFRA21-1 [C], DLCO% predicted [D], and smoking history [S]) was proposed. The scoring system was demonstrated to be as a predictive value for the survival of fibrosing ILD. Nevertheless, serum CEA and CYFRA21-1 levels might be useful for reflecting the severity of fibrosing ILD. However, it still needs further perspective study to verify the power of this scoring system based on multicenter and large population of fibrosing ILD patients.
Some limitations of this study should be noted. First, this was a retrospective and observational study of data obtained from a single center. In addition, the mechanism underlying the association of each biomarker with fibrosing ILD remains to be clarified in further in vivo and in vitro studies.