哮喘-慢性阻塞性肺疾病重叠（ACO）患者肺部气道炎症变化：支气管镜下经支气管活检研究。
Airway inflammatory changes in the lungs of patients with asthma-COPD overlap (ACO): a bronchoscopy endobronchial biopsy study.
机构信息
Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Locked Bag, 1322, Newnham Drive, Launceston, TAS, 7248, Australia.
Launceston Respiratory and Sleep Centre, Launceston, TAS, 7250, Australia.
出版信息
Respir Res. 2023 Sep 12;24(1):221. doi: 10.1186/s12931-023-02527-x.
BACKGROUND
Although asthma and chronic obstructive pulmonary disease (COPD) are two distinct chronic airway inflammatory diseases, they often co-exist in a patient and the condition is referred to as asthma-COPD overlap (ACO). Lack of evidence regarding the inflammatory cells in ACO airways has led to their poor prognosis and treatment. The objective of this endobronchial biopsy (EBB) study was to enumerate inflammatory cellular changes in the airway wall of ACO compared with asthma, COPD current smokers (CS) and ex-smokers (ES), normal lung function smokers (NLFS), and non-smoker controls (HC).
METHODS
EBB tissues from 74 patients were immunohistochemically stained for macrophages, mast cells, eosinophils, neutrophils, CD8+ T-cells and CD4+ T-cells. The microscopic images of stained tissues were evaluated in the epithelium, reticular basement membrane (RBM) cells/mm RBM length, and lamina propria (LP) cells/mm up to a depth of 120 µM using the image analysis software Image-Pro Plus 7.0. The observer was blinded to the images and disease diagnosis. Statistical analysis was performed using GraphPad Prism v9.
RESULTS
The tissue macrophages in ACO were substantially higher in the epithelium and RBM than in HC (P < 0.001 for both), COPD-ES (P < 0.001 for both), and -CS (P < 0.05 and < 0.0001, respectively). The ACO LP macrophages were significantly higher in number than COPD-CS (P < 0.05). The mast cell numbers in ACO were lower than in NLFS (P < 0.05) in the epithelium, lower than COPD (P < 0.05) and NLFS (P < 0.001) in RBM; and lower than HC (P < 0.05) in LP. We noted lower eosinophils in ACO LP than HC (P < 0.05) and the lowest neutrophils in both ACO and asthma. Furthermore, CD8+ T-cell numbers increased in the ACO RBM than HC (P < 0.05), COPD-ES (P < 0.05), and NLFS (P < 0.01); however, they were similar in number in epithelium and LP across groups. CD4+ T-cells remained lower in number across all regions and groups.
CONCLUSION
These results suggest that the ACO airway tissue inflammatory cellular profile differed from the contributing diseases of asthma and COPD with a predominance of macrophages.
背景
尽管哮喘和慢性阻塞性肺疾病（COPD）是两种不同的慢性气道炎症性疾病，但它们经常在患者中同时存在，这种情况被称为哮喘-COPD 重叠（ACO）。由于缺乏关于 ACO 气道中炎症细胞的证据，导致其预后和治疗效果较差。本支气管内膜活检（EBB）研究的目的是比较 ACO 与哮喘、COPD 当前吸烟者（CS）和戒烟者（ES）、正常肺功能吸烟者（NLFS）和非吸烟者对照（HC）气道壁的炎症细胞变化。
方法
对 74 名患者的 EBB 组织进行巨噬细胞、肥大细胞、嗜酸性粒细胞、中性粒细胞、CD8+T 细胞和 CD4+T 细胞的免疫组织化学染色。使用图像分析软件 Image-Pro Plus 7.0 评估染色组织的显微镜图像，在上皮细胞、网状基底膜（RBM）细胞/mm RBM 长度和固有层（LP）细胞/mm 处直至 120µM 深度。观察者对图像和疾病诊断均不知情。使用 GraphPad Prism v9 进行统计分析。
结果
ACO 组织中的巨噬细胞在上皮细胞和 RBM 中的数量明显高于 HC（均 P<0.001）、COPD-ES（均 P<0.001）和 COPD-CS（分别 P<0.05 和 P<0.0001）。ACO LP 中的巨噬细胞数量明显高于 COPD-CS（P<0.05）。ACO 上皮细胞中的肥大细胞数量低于 NLFS（P<0.05），RBM 中的肥大细胞数量低于 COPD（P<0.05）和 NLFS（P<0.001），LP 中的肥大细胞数量低于 HC（P<0.05）。我们注意到 ACO LP 中的嗜酸性粒细胞低于 HC（P<0.05），并且 ACO 和哮喘中的中性粒细胞最低。此外，ACO RBM 中的 CD8+T 细胞数量高于 HC（P<0.05）、COPD-ES（P<0.05）和 NLFS（P<0.01）；然而，它们在各个组的上皮细胞和 LP 中的数量相似。CD4+T 细胞在所有区域和组中的数量仍然较低。
结论
这些结果表明，ACO 气道组织炎症细胞表型与哮喘和 COPD 的致病因素不同，以巨噬细胞为主。
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