中性粒细胞在哮喘中的作用
2021/03/22
摘要
气道炎症在哮喘发病机制中起着关键作用，但其本质上是异质性的。关于2型、嗜酸性炎症主的哮喘已有重大科学发现，有效的治疗方法包括吸入糖皮质激素和新型生物制剂。然而，研究表明，大约五分之一的哮喘患者气道中性粒细胞比例增加。这些患者往往年龄较大，有潜在的呼吸道致病菌，对传统疗法反应不好。目前，还没有对这些患者的具体治疗方法，如中性粒细胞靶向治疗生物制品。中性粒细胞占外周白细胞总数的70%，在炎症和感染中起着关键的防御作用。这使得它们成为一个有问题的治疗靶点。此外，中性粒细胞的功能与年龄变化有关，随着年龄的增长，其对微生物的杀伤作用减少，活性氧释放增加，细胞外陷阱的产生减少。因此，不同年龄组的患者可能需要不同的治疗策略。成人哮喘患者以中性粒细胞性气道炎症为主的发病机制，可能反映出随着年龄的增长中性粒细胞微生物杀伤缺陷的反作用，导致宿主气道细胞的损伤继而出现黏液高分泌和气道重塑。然而，在儿童哮喘患者中，中性粒细胞与疾病的不良表现相关性较小，可能中性粒细胞在儿童中不是主要致病因素。本综述中，我们探讨了中性粒细胞的募集机制，生命周期中细胞功能的变化及其对哮喘治疗的影响。我们还描述了中性粒细胞哮喘的全球流行情况，重点是澳大利亚、新西兰和北美的原住民。
Neutrophils in asthma: the good, the bad and the bacteria.
Helena Crisford, Elizabeth Sapey, Geraint B Rogers, Steven Taylor, Prasad Nagakumar, Ravi Lokwani, Jodie L Simpson.
Abstract
Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics. Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients. The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic. In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.
气道炎症在哮喘发病机制中起着关键作用，但其本质上是异质性的。关于2型、嗜酸性炎症主的哮喘已有重大科学发现，有效的治疗方法包括吸入糖皮质激素和新型生物制剂。然而，研究表明，大约五分之一的哮喘患者气道中性粒细胞比例增加。这些患者往往年龄较大，有潜在的呼吸道致病菌，对传统疗法反应不好。目前，还没有对这些患者的具体治疗方法，如中性粒细胞靶向治疗生物制品。中性粒细胞占外周白细胞总数的70%，在炎症和感染中起着关键的防御作用。这使得它们成为一个有问题的治疗靶点。此外，中性粒细胞的功能与年龄变化有关，随着年龄的增长，其对微生物的杀伤作用减少，活性氧释放增加，细胞外陷阱的产生减少。因此，不同年龄组的患者可能需要不同的治疗策略。成人哮喘患者以中性粒细胞性气道炎症为主的发病机制，可能反映出随着年龄的增长中性粒细胞微生物杀伤缺陷的反作用，导致宿主气道细胞的损伤继而出现黏液高分泌和气道重塑。然而，在儿童哮喘患者中，中性粒细胞与疾病的不良表现相关性较小，可能中性粒细胞在儿童中不是主要致病因素。本综述中，我们探讨了中性粒细胞的募集机制，生命周期中细胞功能的变化及其对哮喘治疗的影响。我们还描述了中性粒细胞哮喘的全球流行情况，重点是澳大利亚、新西兰和北美的原住民。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Thorax. 2021 Feb 25;thoraxjnl-2020-215986. doi: 10.1136/thoraxjnl-2020-215986.)
(Thorax. 2021 Feb 25;thoraxjnl-2020-215986. doi: 10.1136/thoraxjnl-2020-215986.)
Neutrophils in asthma: the good, the bad and the bacteria.
Helena Crisford, Elizabeth Sapey, Geraint B Rogers, Steven Taylor, Prasad Nagakumar, Ravi Lokwani, Jodie L Simpson.
Abstract
Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics. Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients. The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic. In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.
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重症哮喘的免疫反应与急性发作
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肥大细胞源性的5-羟色胺增强乙酰甲胆碱诱导的屋尘螨诱发的实验性哮喘的气道高反应性
