Inflammatory mechanisms in patients with chronic obstructive pulmonary disease
Inflammatory mechanisms in patients with chronic obstructive pulmonary disease
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慢性阻塞性肺疾病患者的炎症机制
DOI：
10.1016/j.jaci.2016.05.011
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发表时间：
2016-07-01
影响因子：
14.2
通讯作者：
Barnes, Peter J.
中科院分区：
文献类型：
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作者：
Barnes, Peter J.
慢性阻塞性肺疾病（COPD）与慢性炎症有关，主要影响肺实质和外周气道，导致大部分不可逆和进行性气流限制。这种炎症的特征是肺泡巨噬细胞、中性粒细胞、T淋巴细胞（主要是T（C）1、T（H）1和T（H）17细胞）和从循环中募集的先天性淋巴样细胞数量增加。这些细胞和结构细胞，包括上皮和内皮细胞以及成纤维细胞，分泌多种促炎介质，包括细胞因子、趋化因子、生长因子和脂质介质。虽然大多数COPD患者主要为嗜酸性粒细胞炎症，但有些患者嗜酸性粒细胞计数增加，这可能是由T（H）2细胞和2型先天淋巴细胞通过上皮细胞释放IL-33引起的。这些患者可能对皮质类固醇和支气管扩张剂更敏感。氧化应激在驱动COPD相关炎症中起关键作用，即使在戒烟者中也是如此，并且可能导致促炎性转录因子核因子κ B（NF-κ B）的激活、抗蛋白酶防御受损、DNA损伤、细胞衰老、自身抗体产生以及通过组蛋白脱乙酰酶2失活的皮质类固醇抗性。全身性炎症也见于COPD患者，并可加重合并症，如心血管疾病、糖尿病和骨质疏松症。COPD患者肺部的加速老化也会导致肺部衰老细胞释放炎性蛋白。在未来，识别对更特异性治疗具有最佳应答的患者的表型将是重要的，并且鉴定治疗表型的生物标志物的开发将是重要的。
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly T(C)1, T(H)1, and T(H)17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by T(H)2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor kappa B (NF-kappa B), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important.