1 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado.
2 COPD Program, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, and.
Am J Respir Crit Care Med. 2018 Apr 1;197(7):885-896. doi: 10.1164/rccm.201704-0667OC.
Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, prediagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired.
To examine airway basal progenitor cells and lung function in smokers with and without COPD.
Bronchial biopsies taken from smokers at risk for COPD and lung cancer were used to acquire airway basal progenitor cells. They were evaluated for count, self-renewal, and multipotentiality (ability to differentiate to basal, mucous, and ciliated cells), and progenitor count was examined for its relationship with lung function.
Basal progenitor count, self-renewal, and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors produced an epithelium with increased basal and mucous cells and decreased ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated with lung function and identified a subset of subjects without COPD with lung function that was midway between non-COPD with high progenitor counts and those with COPD.
Basal progenitor dysfunction relates to the histologic and physiologic manifestations of COPD and identifies a subset that may represent an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is involved in COPD pathogenesis.
多达 40%的吸烟者在几十年的时间里会发展为慢性阻塞性肺疾病（COPD）。尽管 COPD 非常重要，但人们对其易感性和发病机制仍有很多需要了解，尤其是在疾病的早期和诊断前阶段。气道基底祖细胞对于肺部健康和恢复能力至关重要，因为它们能够修复受损的气道。在 COPD 中，正常的气道上皮被增加的基底和分泌（粘液）细胞以及减少的纤毛细胞所取代，这表明祖细胞受损。
检查有和没有 COPD 的吸烟者的气道基底祖细胞和肺功能。
从有 COPD 和肺癌风险的吸烟者的支气管活检中获取气道基底祖细胞。评估其计数、自我更新和多能性（分化为基底、粘液和纤毛细胞的能力），并检查祖细胞计数与肺功能的关系。
与非 COPD 相比，COPD 患者的基底祖细胞计数、自我更新和多能性均降低。COPD 祖细胞产生的上皮细胞中基底和粘液细胞增加，纤毛细胞减少，复制了 COPD 的表型。祖细胞耗竭与肺功能相关，并确定了一组非 COPD 患者，其肺功能位于高祖细胞计数的非 COPD 患者和 COPD 患者之间。
基底祖细胞功能障碍与 COPD 的组织学和生理学表现有关，并确定了一组可能代表 COPD 的早期和诊断前阶段，表明祖细胞耗竭参与了 COPD 的发病机制。
