Development of a scoring system with multidimensional markers for fibrosing interstitial lung disease


The present study retrospectively compared clinical and follow-up data between 259 survivors and 80 deceased with fibrosing PID in the bypass cohort. In this study, we demonstrated that smoking history, age, ACE, CYFRA21-1 and % DLCO predicted could independently predict the survival of patients with fibrosing IPD. A new predictive scoring system named ACDS (age [A]CEA and CYFRA21-1 [C]DLCO% predicted [D]and smoking history [S]) has been proposed. Importantly, we found that the level of the scoring system was strongly associated with the prognosis of patients with fibrosing IPD. Additionally, we demonstrated that patients with a relatively low ACDS score had significantly longer overall survival than patients with a relatively high ACDS score in the validation cohort.

Fibrosing PID had similar biological and clinical behaviors, characterized by progressive deterioration of lung function, progressive deterioration of lung function and high mortality rate12.13. Studying the prognostic value of markers across fibrosing ILD was of great importance for clinical evaluation and continues to elucidate the approach to the management of fibrosing ILD. In recent years, several serum markers have been identified as simple and easily accessible biomarkers to predict survival and severity of fibrotic PID. Research has investigated tumor markers such as CEA, carbohydrate antigen 19–9 (CA 19–9), and CYFRA21-1 that may reflect the severity and prognosis of fibrosing PID14,15,16. A retrospective study by Fahim A et al., which included 41 non-smoking patients with idiopathic pulmonary fibrosis (IPF), reported that serum ACE concentration was elevated in approximately half of patients with IPF and correlated with the severity of the disease17. These results were consistent with the findings of our study on ACE as a biomarker in patients with fibrotic LID. In our study, ACE was identified as an independent prognostic factor for fibrotic PID. CEA is a glycoprotein involved in cell adhesion and is produced by the colonic epithelium. CEA has been reported to localize to the metaplastic epithelium lining the honeycomb bronchioles by immunohistochemical staining. As cuboid pneumocytes are the predominant source of epithelial turnover in severe lung injury 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 the group of deceased individuals with fibrosing PID. In a study by Vercauteren et al., a higher level of CYFRA 21–1 in the BAL of patients with IPF resulted in worse survival compared to the low counterpart CYFRA 21–119. CYFRA21-1 expression in the lung has been identified in bronchiolar epithelial cells and pneumocytes. Elevated serum CYFRA21-1 concentration could be associated with lysis or regeneration of these cells15. Additionally, we demonstrated that serum CEA and CYFRA21-1 were significantly correlated with the decrease in DLCO% predicted in this study. ILD severity is usually based on pulmonary function test results such as predicted DLCO percentage20. Thus, serum levels of CEA and CYFRA21-1 might be useful in reflecting the severity of fibrosing PID.

A large number of studies have reported that smoking is strongly associated with the onset and progression of pulmonary fibrosis21.22. A possible explanation could be that cigarettes contain cytotoxic, mutagenic and pro-inflammatory substances. According to previous reports, these substances caused cellular oxidative stress, increased apoptosis of epithelial cells and dysregulation of immune responses, responsible for the progression of pulmonary fibrosis.23.24. In addition, smoking affects the function of macrophages. It induced macrophage polarization towards the M2 phenotype which enhances inflammation regression and tissue remodeling25. Therefore, smoking cessation might be a good way to slow the development of pulmonary fibrosis in patients with PID.

In recent years, few models have been proposed to predict IPF severity and prognosis. The Glasgow Prognostic Score (GPS) has been reported to play an important role in predicting mortality in patients with acute IPF exacerbation.26. In our study, smoking history, age, CEA, CYFRA21-1 and predicted DLCO% were identified as independent factors to predict the prognosis of fibrosing PID. Moreover, based on these variables, a new predictive scoring system named ACDS (age [A]CEA and CYFRA21-1 [C]DLCO% predicted [D]and smoking history [S]) has been proposed. The scoring system was found to be a predictor of fibrosing ILD survival. However, there remains to be studied in perspective to verify the power of this scoring system based on a multicenter and large population of patients with fibrosing IPD.

Some limitations of this study should be noted. First, this was a retrospective, observational study of data obtained from a single center. Moreover, the mechanism underlying the association of each biomarker with fibrosing PID remains to be clarified in further in vivo and in vitro studies.


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