Rabe Klaus F, Rennard Stephen, Martinez Fernando J, Celli Bartolome R, Singh Dave, Papi Alberto, Bafadhel Mona, Heble Jigna, Radwan Amr, Soler Xavier, Jacob Nara Juby A, Deniz Yamo, Rowe Paul J
LungenClinic Grosshansdorf, Grosshansdorf, Germany.
Christian Albrechts University of Kiel, Kiel, Germany.
Am J Respir Crit Care Med. 2023 Aug 15;208(4):395-405. doi: 10.1164/rccm.202303-0455CI.
Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, progressive inflammatory airway disease associated with a significant impact on patients' lives, including morbidity and mortality, and significant healthcare costs. Current pharmacologic strategies, including first- and second-line therapies such as long-acting β-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, and macrolides, provide relief to patients with COPD. However, many patients remain symptomatic, with persistent symptoms and/or acute exacerbations and progressive lung function loss. Although neutrophilic inflammation is the most common type of inflammation in COPD, 20-40% of patients with COPD exhibit type 2 inflammation, with roles for CD4 (cluster of differentiation 4) T-helper cell type 1 cells, type 2 innate lymphoid cells, eosinophils, and alternatively activated macrophages. On the basis of the current limitations of available therapies, a significant unmet need exists in COPD management, including the need for targeted therapies to address the underlying pathophysiology leading to disease progression, such as type 2 inflammation, as well as biomarkers to help select the patients who would most benefit from the new therapies. Significant progress is being made, with evolving understanding of the pathobiology of COPD leading to novel therapeutic targets including epithelial alarmins. In this review, we describe the current therapeutic landscape in COPD, discuss unmet treatment needs, review the current knowledge of type 2 inflammation and epithelial alarmins in COPD, explore potential biomarkers of type 2 inflammation in COPD, and finally provide a rationale for incorporating therapies targeting type 2 inflammation and epithelial alarmins in COPD. available online at www.atsjournals.org.
慢性阻塞性肺疾病（COPD）是一种复杂、异质性、进行性的炎症性气道疾病，对患者的生活有重大影响，包括发病率和死亡率，以及高昂的医疗费用。目前的药物治疗策略，包括一线和二线疗法，如长效β受体激动剂、长效毒蕈碱拮抗剂、吸入性糖皮质激素、磷酸二酯酶-4抑制剂和大环内酯类药物，可为COPD患者提供缓解。然而，许多患者仍有症状，存在持续症状和/或急性加重以及肺功能进行性丧失。虽然中性粒细胞炎症是COPD中最常见的炎症类型，但20%-40%的COPD患者表现为2型炎症，涉及CD4（分化簇4）1型辅助性T细胞、2型固有淋巴细胞、嗜酸性粒细胞和交替活化的巨噬细胞。基于现有疗法目前的局限性，COPD管理中存在重大未满足需求，包括需要针对性疗法来解决导致疾病进展的潜在病理生理学问题，如2型炎症，以及需要生物标志物来帮助选择最能从新疗法中获益的患者。随着对COPD病理生物学的不断理解，包括上皮警报素在内的新治疗靶点不断涌现，正在取得重大进展。在这篇综述中，我们描述了COPD目前的治疗现状，讨论未满足的治疗需求，回顾目前对COPD中2型炎症和上皮警报素的认识，探索COPD中2型炎症的潜在生物标志物，最后为在COPD中纳入针对2型炎症和上皮警报素的疗法提供理论依据。可在www.atsjournals.org在线获取。
