Maestrelli P, Saetta M, Mapp C E, Fabbri L M
Department of Environmental Medicine and Public Health, University of Padua, Padua, Italy.
Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S76-80. doi: 10.1164/ajrccm.164.supplement_2.2106067.
Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8(+) cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8(+) cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.
气道上皮是抵御有毒吸入物的第一道防线。在一些个体中，吸烟会引发气道炎症、黏液分泌过多以及气流受限且难以逆转，但其机制在很大程度上仍不清楚。同样，为何只有部分吸烟者会患上慢性阻塞性肺疾病（COPD）也尚不明确。在COPD中，有两种细胞类型始终与慢性气流受限相关：中性粒细胞和CD8(+)细胞。中性粒细胞分布于气道和肺泡腔的黏膜表面，即上皮和管腔，而CD8(+)细胞在气道和肺实质的上皮下区域分布更为广泛，包括肺泡壁和动脉。在轻度或中度COPD患者中可观察到这种炎症细胞分布模式，且在已患COPD的患者中，这种模式不会因戒烟而改变。在重度COPD患者的黏膜下层，中性粒细胞数量进一步增加，表明这些细胞在疾病进展中发挥作用。黏液分泌过多是COPD的主要表现之一。黏液由气道上皮内衬的支气管腺体和杯状细胞产生。与黏液腺肿大不同，更大程度的黏膜炎症与痰液产生相关。虽然黏膜下腺体的中性粒细胞浸润仅发生在患有COPD的吸烟者中，但外周气道的杯状细胞增生在患有或未患COPD的吸烟者中均会出现，这表明杯状细胞增生的主要决定因素是香烟烟雾本身。
