炎症依赖及炎症非依赖的气道重塑
2018/07/09
摘要
背景与目的：哮喘的病理特征是气道炎症(粒细胞（GA）或寡粒细胞（PGA）)和气道结构的重塑。然而，炎症表型和气道重塑之间的关系尚不清楚。我们假设哮喘气道重塑的某些特征依赖于粒细胞气道炎症，而另一些则不是。
方法：对对照组（n=48）和气道内有（n=51）或无（n=29）粒细胞炎症的哮喘患者的死后气道切片进行研究。估计气道平滑肌层（ASM）、基底膜和内外气道壁的厚度、平滑肌细胞的大小和数目、平滑肌层内细胞外基质的体积分数、平滑肌细胞缩短和管腔粘液。比较三组患者的气道直径大小。
结果：在气道寡细胞炎症的情况下，只有平滑肌层和基底膜的厚度与对照组相比增加。而在粒细胞炎症表型的情况下，与对照组相比不仅有平滑肌层和基底膜厚度增加，还有内外气道壁厚度的增加，平滑肌层收缩和粘液阻塞更是导致气道管腔狭窄程度增加。在致命性哮喘的病例中更常观察到粒细胞炎症表型存在。
结论：这些结果表明，内壁和外壁增厚增加与气道炎症相关，而即使在没有炎症细胞的情况下平滑肌层和基底膜的增厚也可能增加。因此，平滑肌层和基底膜的重塑可能不易受到抗炎治疗的影响。
Inflammation-dependent and independent airway remodelling in asthma.
Elliot JG, Noble PB, Mauad T, Bai TR, Abramson MJ, McKay KO, Green FHY, James AL.
Abstract
BACKGROUND AND OBJECTIVE: The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not.
METHODS: Post-mortem airway sections from control subjects (n = 48) and cases of asthma with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway wall were studied. The thickness of the airway smooth muscle (ASM) layer, basement membrane and inner and outer airway walls, the size and number of ASM cells, the volume fraction of extracellular matrix within the ASM layer, ASM shortening and luminal mucus were estimated. Airway dimensions were compared between the three subject groups.
RESULTS: In cases of PGA, only the thickness of the ASM layer and basement membrane was increased compared with control subjects. In cases of GA, not only the ASM and basement membrane were increased in thickness, but there was also increased inner and outer airway wall thickness and increased narrowing of the airway lumen due to ASM shortening and mucus obstruction, compared with control subjects. Granulocytic inflammation was observed more often in cases of fatal asthma.
CONCLUSION: These findings suggest that inner and outer wall thickening coexists with inflammation, whereas thickening of the ASM layer and basement membrane may be present even in the absence of inflammation. Remodelling of the ASM layer and basement membrane may therefore be less susceptible to anti-inflammatory therapy.
背景与目的：哮喘的病理特征是气道炎症(粒细胞（GA）或寡粒细胞（PGA）)和气道结构的重塑。然而，炎症表型和气道重塑之间的关系尚不清楚。我们假设哮喘气道重塑的某些特征依赖于粒细胞气道炎症，而另一些则不是。
方法：对对照组（n=48）和气道内有（n=51）或无（n=29）粒细胞炎症的哮喘患者的死后气道切片进行研究。估计气道平滑肌层（ASM）、基底膜和内外气道壁的厚度、平滑肌细胞的大小和数目、平滑肌层内细胞外基质的体积分数、平滑肌细胞缩短和管腔粘液。比较三组患者的气道直径大小。
结果：在气道寡细胞炎症的情况下，只有平滑肌层和基底膜的厚度与对照组相比增加。而在粒细胞炎症表型的情况下，与对照组相比不仅有平滑肌层和基底膜厚度增加，还有内外气道壁厚度的增加，平滑肌层收缩和粘液阻塞更是导致气道管腔狭窄程度增加。在致命性哮喘的病例中更常观察到粒细胞炎症表型存在。
结论：这些结果表明，内壁和外壁增厚增加与气道炎症相关，而即使在没有炎症细胞的情况下平滑肌层和基底膜的增厚也可能增加。因此，平滑肌层和基底膜的重塑可能不易受到抗炎治疗的影响。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Respirology. 2018 Jun 26.)
(Respirology. 2018 Jun 26.)
Inflammation-dependent and independent airway remodelling in asthma.
Elliot JG, Noble PB, Mauad T, Bai TR, Abramson MJ, McKay KO, Green FHY, James AL.
Abstract
BACKGROUND AND OBJECTIVE: The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not.
METHODS: Post-mortem airway sections from control subjects (n = 48) and cases of asthma with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway wall were studied. The thickness of the airway smooth muscle (ASM) layer, basement membrane and inner and outer airway walls, the size and number of ASM cells, the volume fraction of extracellular matrix within the ASM layer, ASM shortening and luminal mucus were estimated. Airway dimensions were compared between the three subject groups.
RESULTS: In cases of PGA, only the thickness of the ASM layer and basement membrane was increased compared with control subjects. In cases of GA, not only the ASM and basement membrane were increased in thickness, but there was also increased inner and outer airway wall thickness and increased narrowing of the airway lumen due to ASM shortening and mucus obstruction, compared with control subjects. Granulocytic inflammation was observed more often in cases of fatal asthma.
CONCLUSION: These findings suggest that inner and outer wall thickening coexists with inflammation, whereas thickening of the ASM layer and basement membrane may be present even in the absence of inflammation. Remodelling of the ASM layer and basement membrane may therefore be less susceptible to anti-inflammatory therapy.
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哮喘患儿肺功能的整合转录组学和代谢组学研究
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寡细胞型哮喘：气道阻塞与炎症的解偶联
