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哮喘和慢性阻塞性肺疾病的共同发病机制——来自遗传学研究的见解

Common Pathogeneses Underlying Asthma and Chronic Obstructive Pulmonary Disease -Insights from Genetic Studies.

作者信息

Hizawa Nobuyuki

机构信息

Department of Pulmonary Medicine, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.

出版信息

Int J Chron Obstruct Pulmon Dis. 2024 Mar 4;19:633-642. doi: 10.2147/COPD.S441992. eCollection 2024.

DOI:10.2147/COPD.S441992
PMID:38464563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10922945/
Abstract

Neither asthma nor chronic obstructive pulmonary disease (COPD) is a single disease consisting of a uniform pathogenesis; rather, they are both syndromes that result from a variety of basic distinct pathogeneses. Many of the basic pathogeneses overlap between the two diseases, and multiple basic pathogeneses are simultaneously involved at varying proportions in individual patients. The specific combination of different basic pathogeneses in each patient determines the phenotype of the patient, and it varies widely from patient to patient. For example, type 2 airway inflammation and neutrophilic airway inflammation may coexist in the same patient, and quite a few patients have clinical characteristics of both asthma and COPD. Even in the same patient, the contribution of each pathogenesis is expected to differ at different life stages (eg, childhood, adolescence, middle age, and older), during different seasons (eg, high seasons for hay fever and rhinovirus infection), and depending on the nature of treatments. This review describes several basic pathogeneses commonly involved in both asthma and COPD, including chronic non-type 2 inflammation, type 2 inflammation, viral infections, and lung development. Understanding of the basic molecular pathogeneses in individual patients, rather than the use of clinical diagnosis, such as asthma, COPD, or even asthma COPD overlap, will enable us to better deal with the diversity seen in disease states, and lead to optimal treatment practices tailored for each patient with less disease burden, such as drug-induced side effects, and improved prognosis. Furthermore, we can expect to focus on these molecular pathways as new drug discovery targets.

摘要

哮喘和慢性阻塞性肺疾病(COPD)都不是由单一统一发病机制构成的单一疾病;相反,它们都是由多种基本不同发病机制导致的综合征。这两种疾病的许多基本发病机制相互重叠,并且多种基本发病机制在个体患者中以不同比例同时存在。每个患者不同基本发病机制的具体组合决定了患者的表型,而且患者之间差异很大。例如,2型气道炎症和嗜中性粒细胞气道炎症可能在同一患者中共存,相当多的患者同时具有哮喘和COPD的临床特征。即使在同一患者中,每种发病机制在不同生命阶段(如儿童期、青春期、中年和老年)、不同季节(如花粉热和鼻病毒感染高发季节)以及取决于治疗性质时的作用也可能不同。本综述描述了哮喘和COPD中常见的几种基本发病机制,包括慢性非2型炎症、2型炎症、病毒感染和肺发育。了解个体患者的基本分子发病机制,而非使用临床诊断(如哮喘、COPD甚至哮喘-COPD重叠),将使我们能够更好地应对疾病状态中所见的多样性,并导致为每个患者量身定制的最佳治疗方案,减少疾病负担(如药物引起的副作用)并改善预后。此外,我们有望将这些分子途径作为新的药物发现靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/570fc4f80224/COPD-19-633-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/267e49da68ee/COPD-19-633-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/555f34f46554/COPD-19-633-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/60b11b3d60d8/COPD-19-633-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/570fc4f80224/COPD-19-633-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/267e49da68ee/COPD-19-633-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/555f34f46554/COPD-19-633-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/60b11b3d60d8/COPD-19-633-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bbf/10922945/570fc4f80224/COPD-19-633-g0004.jpg

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J Allergy Clin Immunol. 2023 Dec;152(6):1423-1432. doi: 10.1016/j.jaci.2023.08.002. Epub 2023 Aug 16.
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Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.气道平滑肌面积预测 COPD 患者三联治疗(HISTORIC)中对类固醇的反应:一项随机、安慰剂对照、双盲、研究者发起的试验。
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Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts.针对嗜酸性粒细胞计数提示 2 型炎症的 COPD,应用度普利尤单抗。
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