Araújo Márcia, Beltrão Marília, Sokhatska Oksana, Melo Natália, Caetano Mota Patrícia, Bastos Helder Novais, Terras André, Coelho David, Delgado Luís, Morais António
Department of Pulmonology, Hospital Pedro Hispano, Matosinhos, Portugal.
Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, Porto, Portugal.
ERJ Open Res. 2024 Dec 9;10(6). doi: 10.1183/23120541.00553-2024. eCollection 2024 Nov.
Progressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs. This study aimed to investigate the role of serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.
Newly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline and disease progression was monitored. PPF was defined according to the recent European Respiratory Society, American Thoracic Society, Japanese Respiratory Society and the Latin American Thoracic Society Clinical Practice Guidelines.
79 patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (adjusted OR 1.263, 95% CI 1.029-1.551; p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.
In patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.
进行性肺纤维化（PPF）对应于除特发性肺纤维化（IPF）以外的任何纤维化间质性肺疾病（ILD），其呈现出与IPF相似的疾病进展的临床、生理和/或放射学证据。基质金属蛋白酶（MMPs）与肺纤维化的发病机制有关，并且与IPF和其他纤维化ILD的疾病进展及生存率降低相关。本研究旨在调查血清MMP-1和MMP-7水平在纤维化非IPF ILD患者中的作用，作为可能发展为PPF的风险患者的生物标志物。
新诊断的纤维化非IPF ILD患者纳入本研究。在基线时对血清MMP-1和MMP-7水平进行定量，并监测疾病进展。PPF根据最近的欧洲呼吸学会、美国胸科学会、日本呼吸学会和拉丁美洲胸科学会临床实践指南进行定义。
纳入79例纤维化非IPF ILD患者，并分为PPF组或非PPF组。在PPF组中检测到MMP-7水平显著更高，但MMP-1水平未升高（p = 0.01）。在对性别、年龄和吸烟史进行调整后，MMP-7与PPF独立相关（校正后的OR为1.263，95%CI为1.029 - 1.551；p = 0.026）。血清MMP-7水平的截断值为3.53 ng·mL时，预测非IPF ILD患者发生PPF的敏感性为61%，特异性为74%。
在纤维化非IPF ILD患者中，随访时符合PPF标准的患者亚组血清MMP-7水平显著更高。这可作为一种可能的生物标志物进行考虑并进一步研究，以识别有PPF风险的纤维化ILD患者。
