National Heart & Lung Institute, Imperial College London, London, UK
Lung Health Research Centre, University of Melbourne, Melbourne, Australia.
Eur Respir Rev. 2021 Jan 6;30(159). doi: 10.1183/16000617.0213-2020. Print 2021 Mar 31.
COPD and idiopathic pulmonary fibrosis (IPF) together represent a considerable unmet medical need, and advances in their treatment lag well behind those of other chronic conditions. Both diseases involve maladaptive repair mechanisms leading to progressive and irreversible damage. However, our understanding of the complex underlying disease mechanisms is incomplete; with current diagnostic approaches, COPD and IPF are often discovered at an advanced stage and existing definitions of COPD and IPF can be misleading. To halt or reverse disease progression and achieve lung regeneration, there is a need for earlier identification and treatment of these diseases. A precision medicine approach to treatment is also important, involving the recognition of disease subtypes, or endotypes, according to underlying disease mechanisms, rather than the current "one-size-fits-all" approach. This review is based on discussions at a meeting involving 38 leading global experts in chronic lung disease mechanisms, and describes advances in the understanding of the pathology and molecular mechanisms of COPD and IPF to identify potential targets for reversing disease degeneration and promoting tissue repair and lung regeneration. We also discuss limitations of existing disease measures, technical advances in understanding disease pathology, and novel methods for targeted drug delivery.
慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)共同构成了重大的未满足的医疗需求,其治疗进展远远落后于其他慢性疾病。这两种疾病都涉及适应性修复机制,导致进行性和不可逆转的损伤。然而,我们对复杂的潜在疾病机制的理解并不完整;目前的诊断方法,COPD 和 IPF 通常在晚期才被发现,而 COPD 和 IPF 的现有定义可能具有误导性。为了阻止或逆转疾病进展并实现肺再生,需要更早地识别和治疗这些疾病。治疗的精准医学方法也很重要,需要根据潜在的疾病机制来识别疾病亚型或表型,而不是目前的“一刀切”方法。本综述基于一次会议的讨论,该会议涉及 38 位全球慢性肺部疾病机制的领先专家,描述了对 COPD 和 IPF 的病理学和分子机制的理解的进展,以确定逆转疾病退化和促进组织修复和肺再生的潜在靶点。我们还讨论了现有疾病测量方法的局限性、对疾病病理学的技术进展,以及靶向药物输送的新方法。