Clinical significance of interleukin-18 binding protein in the prognosis of idiopathic pulmonary fibrosis

doi:10.3877/cma.j.issn.1674-6902.2025.05.008

Abstract

Abstract:

Objective

To analyze the clinical significance of bronchoalveolar lavage fluid (BALF) and serum interleukin-18 binding protein (IL-18BP) in predicting the prognosis of idiopathic pulmonary fibrosis (IPF).

Methods

Eighty-seven IPF patients admitted to our hospital between January 2019 and December 2023 were prospectively enrolled. All received antifibrotic therapy. Serum and BALF IL-18BP levels were measured using enzyme-linked immunosorbent assay (ELISA). The patients were grouped according to their survival status. 52 surviving cases were assigned to the control group, and 35 deceased cases were assigned to the observation group.

Results

The median serum IL-18BP level across all 87 patients was 3.40 (IQR: 0.67, 120.64) ng/ml, and the median BALF IL-18BP level was 3.12 (IQR: 0.06, 72.97) ng/ml. During a median follow-up of 36 months, 35 patients (40.23%) died. 27 cases (31.03%) experienced acute exacerbation within one year. The observation group had significantly higher serum IL-18BP levels [12.04 (5.05, 33.14)ng/ml] and significantly lower BALF IL-18BP levels [2.53 (1.15, 4.44) ng/ml] compared to the control group [serum: 2.55 (1.82, 3.40) ng/ml, BALF: 3.65 (1.66, 6.25) ng/ml] (P<0.05). Spearman rank correlation analysis revealed a positive correlation between serum and BALF IL-18BP levels (r=0.215, P=0.020). Serum IL-18BP levels were significantly higher in AE patients [56.12 (22.99, 124.37) ng/ml] compared to non-AE patients [4.92(2.39, 11.85) ng/ml] (Z=-4.787, P<0.001). Receiver operating characteristic (ROC) curve analysis showed serum IL-18BP predicted IPF-related death with an area under the curve (AUC) of 0.864, and an optimal cutoff value of 5.10 ng/ml (P<0.05). Multivariate Cox proportional hazards regression analysis identified high serum IL-18BP level as an independent risk factor for poor IPF prognosis (P<0.05). Kaplan-Meier curve analysis showed that among 54 cases with low serum IL-18BP level (<5.10 ng/ml), 47 cases (87.04%) survived, and among 33 cases with high serum IL-18bp level (≥5.10 ng/ml), 5 cases (15.15%) survived. The median OS was 34 and 26 months respectively (χ²=47.795, P<0.001). Spearman rank correlation analysis showed a negative correlation between serum IL-18BP levels and diffusing capacity of the lung for carbon monoxide (DLCO)% predicted (r=-0.193, P=0.037).

Conclusion

High serum IL-18BP levels are associated with a significantly increased risk of poor prognosis in IPF. Serum IL-18BP may serve as a biomarker for early risk stratification in IPF.

Key words: Idiopathic pulmonary fibrosis, Interleukin-18 binding protein, Bronchoalveolar lavage fluid, Prognosis

Qun Li, Hehong Zhao, Junyi Wang, Feng Chen, Jian Shen. Clinical significance of interleukin-18 binding protein in the prognosis of idiopathic pulmonary fibrosis[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 708-713.

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References 30

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临床资料	观察组(n＝35)	对照组(n＝52)	t/χ²/Z	P值
吸烟史[n(%)]			1.767	0.413
从未	9(25.71)	13(25.0)
现在	22(62.86)	29(55.77)
既往	3(8.57)	10(19.23)
吸烟指数[M(M₂₅，M₇₅)]	20.00(1.25，37.50)	20.00(0.00，34.00)	－0.016	0.916
病史[n(%)]
糖尿病	21(40.38)	10(28.57)	1.273	0.259
高血压	20(38.46)	14(40.0)	0.021	0.885
冠心病	14(26.92)	8(22.86)	0.183	0.669
哮喘	0(0.0)	1(2.86)	－	0.402
抗纤维化药物[n(%)]
吡非尼酮	17(48.57)	34(65.38)	2.438	0.118
尼达尼布	7(20.0)	13(25.0)	0.295	0.587
其他用药[n(%)]
乙酰半胱氨酸片	11(31.43)	19(36.54)	0.242	0.623
质子泵抑制剂	7(20.0)	14(26.92)	0.548	0.459
肺功能指标
FVC%[%，(±s)]	79.81±16.87	88.08±17.00	2.232	0.028
FEV₁%[%，(±s)]	93.71±19.26	98.65±20.66	1.123	0.264
DLCO%[%，(±s)]	71.63±20.39	81.98±21.25	2.264	0.026
炎症指标
白细胞计数[×10⁹/L，M(M₂₅，M₇₅)]	7.67(6.35，9.67)	6.68(5.09，9.18)	－1.446	0.148
C反应蛋白[mg/L，M(M₂₅，M₇₅)]	8.10(1.90，34.30)	3.15(1.00，12.98)	－1.558	0.119
红细胞沉降率[mm/1 h，M(M₂₅，M₇₅)]	25.00(10.00，37.00)	17.00(10.00，28.00)	－1.668	0.095

临床资料	观察组(n＝35)	对照组(n＝52)	t/χ²/Z	P值
吸烟史[n(%)]			1.767	0.413
从未	9(25.71)	13(25.0)
现在	22(62.86)	29(55.77)
既往	3(8.57)	10(19.23)
吸烟指数[M(M₂₅，M₇₅)]	20.00(1.25，37.50)	20.00(0.00，34.00)	－0.016	0.916
病史[n(%)]
糖尿病	21(40.38)	10(28.57)	1.273	0.259
高血压	20(38.46)	14(40.0)	0.021	0.885
冠心病	14(26.92)	8(22.86)	0.183	0.669
哮喘	0(0.0)	1(2.86)	－	0.402
抗纤维化药物[n(%)]
吡非尼酮	17(48.57)	34(65.38)	2.438	0.118
尼达尼布	7(20.0)	13(25.0)	0.295	0.587
其他用药[n(%)]
乙酰半胱氨酸片	11(31.43)	19(36.54)	0.242	0.623
质子泵抑制剂	7(20.0)	14(26.92)	0.548	0.459
肺功能指标
FVC%[%，(±s)]	79.81±16.87	88.08±17.00	2.232	0.028
FEV₁%[%，(±s)]	93.71±19.26	98.65±20.66	1.123	0.264
DLCO%[%，(±s)]	71.63±20.39	81.98±21.25	2.264	0.026
炎症指标
白细胞计数[×10⁹/L，M(M₂₅，M₇₅)]	7.67(6.35，9.67)	6.68(5.09，9.18)	－1.446	0.148
C反应蛋白[mg/L，M(M₂₅，M₇₅)]	8.10(1.90，34.30)	3.15(1.00，12.98)	－1.558	0.119
红细胞沉降率[mm/1 h，M(M₂₅，M₇₅)]	25.00(10.00，37.00)	17.00(10.00，28.00)	－1.668	0.095

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