Celli Bartolome R, Anzueto Antonio, Singh Dave, Hanania Nicola A, Fabbri Leonardo, Martinez Fernando J, Soler Xavier, Djandji Michel, Jacob-Nara Juby A, Rowe Paul J, Deniz Yamo, Radwan Amr
Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Department of Medicine, South Texas Veterans Health Care System, San Antonio, TX; Department of Medicine, University of Texas Health San Antonio, San Antonio, TX.
Chest. 2025 May;167(5):1346-1355. doi: 10.1016/j.chest.2024.09.049. Epub 2024 Dec 2.
COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and parenchymal abnormalities, and respiratory symptoms, including dyspnea, fatigue, chronic cough, and sputum production. Cigarette smoke exposure is a major contributor to COPD; however, inhalation of toxic particles and other environmental and host factors can contribute to its genesis. Over time, the clinical course is frequently punctuated by exacerbations that further accelerate lung function decline and increase exacerbation risk. Despite current optimal therapy, many patients remain symptomatic, have exacerbations, and have increased morbidity, mortality, and health care costs. This review focuses on current knowledge of COPD pathophysiology, the role of inflammatory mechanisms, and the potential use of biologics to modulate these mechanisms.
The inflammatory response in COPD includes both type 1 and type 2 immune cells. Type 2 inflammation is suggested by eosinophilia in a significant proportion of patients with COPD. Studies targeting IL-5 in patients with COPD have failed to demonstrate significant reductions in exacerbations, suggesting that eosinophil modulation alone may be insufficient to treat COPD. Based on a better understanding of the disease and role of alarmins, with a broader role in the inflammatory cascade, it is likely that some biologics may benefit certain COPD endotypes. Ongoing trials will provide information about which groups can benefit from the blocking of specific pathways (eg, IL-5, IL-4/IL-13, IL-33, thymic stromal lymphopoietin).
Biologics targeting inflammatory pathways may be effective treatments for specific patients with COPD.
慢性阻塞性肺疾病（COPD）是一种复杂的异质性肺部疾病，其特征为因气道和肺实质异常导致的持续性气流受限，以及包括呼吸困难、疲劳、慢性咳嗽和咳痰等在内的呼吸道症状。接触香烟烟雾是COPD的主要促成因素；然而，吸入有毒颗粒以及其他环境和宿主因素也可促使其发病。随着时间推移，临床病程常因急性加重而中断，急性加重会进一步加速肺功能下降并增加急性加重风险。尽管目前采用了最佳治疗方法，但许多患者仍有症状、会出现急性加重，且发病率、死亡率和医疗费用均有所增加。本综述聚焦于COPD病理生理学的现有知识、炎症机制的作用以及生物制剂调节这些机制的潜在用途。
COPD中的炎症反应包括1型和2型免疫细胞。相当一部分COPD患者出现嗜酸性粒细胞增多，提示存在2型炎症。针对COPD患者的白细胞介素-5（IL-5）的研究未能证明急性加重有显著减少，这表明仅调节嗜酸性粒细胞可能不足以治疗COPD。基于对疾病以及警报素作用的更好理解，警报素在炎症级联反应中发挥更广泛作用，某些生物制剂可能会使特定的COPD内型受益。正在进行的试验将提供有关哪些群体可从阻断特定途径（如IL-5、IL-4/IL-13、IL-33、胸腺基质淋巴细胞生成素）中获益的信息。
针对炎症途径的生物制剂可能是特定COPD患者的有效治疗方法。
