Abstract
间质性肺疾病(ILDs)组成and heterogeneous group of disorders of known and unknown aetiology characterised by diffuse damage of the lung parenchyma. In recent years it has become evident that patients with different types of ILD are at risk of developing progressive pulmonary fibrosis, known as progressive fibrosing ILD (PF-ILD). This is a phenotype that behaves similar to idiopathic pulmonary fibrosis, the archetypical example of progressive fibrosis. PF-ILD is not a distinct clinical entity but describes a group of ILDs with similar clinical behaviour. This phenotype may occur in diseases displaying distinct aetiologies and different biopathology during their initiation and development. Importantly, these entities may have the potential for improvement or stabilisation prior to entering the progressive fibrosing phase. The crucial questions are: 1) why does a subset of patients develop a progressive and irreversible fibrotic phenotype even with appropriate treatment? and 2) what are the possible pathogenic mechanisms driving progression? Here, we provide a framework highlighting putative mechanisms underlying progression, including genetic susceptibility, ageing, epigenetics, structural fibrotic distortion, aberrant composition and stiffness of the extracellular matrix, and the emergence of distinct pro-fibrotic cell subsets. Understanding the cellular and molecular mechanisms behind PF-ILD will provide the basis for identifying risk factors and appropriate therapeutic strategies.
Abstract
ILDs of different aetiologies, which have the potential for improvement or stabilisation, may develop progressive pulmonary fibrosis (PF-ILD). Mechanisms underlying progression, including (epi)genetics, ageing and structural pattern, are proposed in this review.https://bit.ly/2NSJPXQ
Footnotes
Author contributions: M. Selman developed the general concept. M. Selman and A. Pardo contributed equally to the literature search, discussion of the concept, and writing and approval of the final manuscript.
Conflict of interest: M. Selman reports personal fees for consultancy from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: A. Pardo has nothing to disclose.
- ReceivedNovember 2, 2020.
- AcceptedJanuary 27, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contactpermissions{at}ersnet.org