National Heart and Lung Institute, Imperial College, London, United Kingdom.
J Allergy Clin Immunol. 2016 Jul;138(1):16-27. doi: 10.1016/j.jaci.2016.05.011. Epub 2016 May 27.
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 TC1, TH1, and TH17 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 TH2 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 κB (NF-κB), 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.
慢性阻塞性肺疾病（COPD）与慢性炎症相关，主要影响肺实质和外周气道，导致气流受限基本上不可逆转和进行性加重。这种炎症的特征是肺泡巨噬细胞、中性粒细胞、T 淋巴细胞（主要为 TC1、TH1 和 TH17 细胞）和从循环中募集的固有淋巴细胞数量增加。这些细胞和结构细胞，包括上皮细胞和内皮细胞以及成纤维细胞，分泌各种促炎介质，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 患者的炎症主要为中性粒细胞，但有些患者的嗜酸性粒细胞计数增加，这可能是由 TH2 细胞和 2 型固有淋巴细胞通过上皮细胞释放白细胞介素-33 协调的。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 相关炎症中起着关键作用，即使在已戒烟者中也是如此，并且可能导致促炎转录因子核因子 κB（NF-κB）的激活、抗蛋白酶防御受损、DNA 损伤、细胞衰老、自身抗体产生和皮质类固醇抵抗，通过组蛋白去乙酰化酶 2 的失活。COPD 患者也存在系统性炎症，可使心血管疾病、糖尿病和骨质疏松等合并症恶化。COPD 患者肺部的加速衰老也会导致肺内衰老细胞释放炎症蛋白。在未来，重要的是要认识到对更特异性治疗有最佳反应的患者表型，开发识别治疗表型的生物标志物将是重要的。
