Mondoni Michele, Rinaldo Rocco, Ryerson Christopher J, Albrici Cristina, Baccelli Andrea, Tirelli Claudio, Marchetti Francesca, Cefalo Jacopo, Nalesso Giulia, Ferranti Giulia, Alfano Fausta, Sotgiu Giovanni, Guazzi Marco, Centanni Stefano
Department of Health Sciences, Respiratory Unit, ASST Santi Paolo e Carlo, Università degli Studi di Milano, Milan, Italy.
Department of Medical Sciences, Respiratory Diseases Unit, AOU Città della Salute e della Scienza di Torino, Molinette Hospital, University of Turin, Turin, Italy.
ERJ Open Res. 2024 Nov 25;10(6). doi: 10.1183/23120541.00550-2024. eCollection 2024 Nov.
Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing and progressive interstitial lung disease of unknown aetiology with a pathogenesis still partly unknown. Several microvascular and macrovascular abnormalities have been demonstrated in the pathogenesis of IPF and related pulmonary hypertension (PH), a complication of the disease.
We carried out a non-systematic, narrative literature review aimed at describing the role of the vasculature in the natural history of IPF.
The main molecular pathogenetic mechanisms involving vasculature ( endothelial-to-mesenchymal transition, vascular remodelling, endothelial permeability, occult alveolar haemorrhage, vasoconstriction and hypoxia) and the genetic basis of vascular remodelling are described. The prevalence and clinical relevance of associated PH are highlighted with focus on the vasculature as a prognostic marker. The vascular effects of current antifibrotic therapies, the role of pulmonary vasodilators in the treatment of disease, and new pharmacological options with vascular-targeted activity are described.
The vasculature plays a key role in the natural history of IPF from the early phases of disease until development of PH in a subgroup of patients, a complication related to a worse prognosis. Pulmonary vascular volume has emerged as a novel computed tomography finding and a predictor of mortality, independent of PH. New pharmacological options with concomitant vascular-directed activity might be promising in the treatment of IPF.
特发性肺纤维化（IPF）是一种病因不明的慢性、纤维化且进行性的间质性肺病，其发病机制仍部分未知。在IPF及其并发症——相关肺动脉高压（PH）的发病机制中，已证实存在多种微血管和大血管异常。
我们进行了一项非系统性的叙述性文献综述，旨在描述血管系统在IPF自然病程中的作用。
描述了涉及血管系统的主要分子发病机制（内皮-间充质转化、血管重塑、内皮通透性、隐匿性肺泡出血、血管收缩和缺氧）以及血管重塑的遗传基础。强调了相关PH的患病率及其临床相关性，重点关注血管系统作为一种预后标志物的作用。描述了当前抗纤维化治疗的血管效应、肺血管扩张剂在疾病治疗中的作用以及具有血管靶向活性的新药理学选择。
从疾病早期到一部分患者发生PH（一种与较差预后相关的并发症），血管系统在IPF的自然病程中起着关键作用。肺血管容积已成为一种新的计算机断层扫描发现和死亡率预测指标，独立于PH。具有同时血管靶向活性的新药理学选择在IPF治疗中可能很有前景。
