Article(id=1199703040207979321, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199703037368430831, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1493.2023.0413, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1657123200000, receivedDateStr=2022-07-07, revisedDate=null, revisedDateStr=null, acceptedDate=1667577600000, acceptedDateStr=2022-11-05, onlineDate=1763961094190, onlineDateStr=2025-11-24, pubDate=1701100800000, pubDateStr=2023-11-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763961094190, onlineIssueDateStr=2025-11-24, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763961094190, creator=13701087609, updateTime=1763961094190, updator=13701087609, issue=Issue{id=1199703037368430831, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='11', pageStart='1237', pageEnd='1358', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763961093513, creator=13701087609, updateTime=1763961140964, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1199703236451070744, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199703037368430831, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1199703236451070745, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199703037368430831, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1353, endPage=1358, ext={EN=ArticleExt(id=1199703040526746433, articleId=1199703040207979321, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Research progress of immunocytes and immunologic factors related to acute exacerbation of chronic obstructive pulmonary disease, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Chronic obstructive pulmonary disease (COPD) is a frequent and common disease of the respiratory system. The problem of low early diagnosis rate, low treatment compliance, and low treatment standardization has persisted in the diagnosis and treatment of COPD. Heterogeneity found in clinical practice is one of the reasons why COPD is difficult to treat. In recent years, it has been gradually recognized that the occurrence and development of COPD are closely related to the immune state of the body. At present, it become one of the hot spots in clinical and basic research that searching for specific and sensitive cell and molecular biomarkers to early diagnose acute exacerbation and subtype differentiation of COPD, which ultimately provide individual diagnosis and treatment strategies for COPD patients. This review focuses on the research progress of immunocytes and immunologic factors as biomarkers to different phenotypes and progression of COPD in recent years, providing a reference for the research on diagnosis and treatment of COPD.

, correspAuthors=Li Xiao, authorNote=null, correspAuthorsNote=
E-mail:
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慢性阻塞性肺疾病(COPD)是呼吸系统的多发病和常见病,且一直存在早期诊断率低、治疗依从性低、治疗规范性低等问题。临床实践显示,COPD的异质性是其治疗困难的原因之一。近年来逐渐认识到COPD的发生发展与机体免疫状态密切相关,多项研究试图寻找特异性强、灵敏度高的细胞与分子生物标记物,以早期诊断COPD急性加重并进行亚型区分,为COPD患者提供个体化的诊疗策略。本文综述近年来与不同表型COPD及疾病进展密切相关的免疫细胞及因子作为生物标志物的研究进展,旨在为COPD的诊断与治疗研究提供参考。

, correspAuthors=肖漓, authorNote=null, correspAuthorsNote=
肖漓,E-mail:
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李蕊,硕士研究生,主要从事肺疾病实验室检验诊断方面的研究

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慢性阻塞性肺疾病急性加重相关的免疫细胞及因子研究进展
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李蕊 1, 2 , 肖漓 2, *
解放军医学杂志 | 综述 2023,48(11): 1353-1358
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解放军医学杂志 | 综述 2023, 48(11): 1353-1358
慢性阻塞性肺疾病急性加重相关的免疫细胞及因子研究进展
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李蕊1, 2, 肖漓2, *
作者信息
  • 1河北北方学院研究生学院,河北张家口 075000
  • 2解放军总医院第八医学中心呼吸与危重症医学部研究所/北京市器官移植与免疫调节重点实验室,北京 100091
  • 李蕊,硕士研究生,主要从事肺疾病实验室检验诊断方面的研究

通讯作者:

肖漓,E-mail:
Research progress of immunocytes and immunologic factors related to acute exacerbation of chronic obstructive pulmonary disease
Rui Li1, 2, Li Xiao2, *
Affiliations
  • 1Graduate School, Hebei North University, Zhangjiakou, Hebei 075000, China
  • 2Institute of Respiratory and Critical Care Medicine/Beijing Key Laboratory of Organ Transplantation and Immunology Regulatory, the Eighth Medical Center of Chinese PLA General Hospital, Beijing 100091, China
出版时间: 2023-11-28 doi: 10.11855/j.issn.0577-7402.1493.2023.0413
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慢性阻塞性肺疾病(COPD)是呼吸系统的多发病和常见病,且一直存在早期诊断率低、治疗依从性低、治疗规范性低等问题。临床实践显示,COPD的异质性是其治疗困难的原因之一。近年来逐渐认识到COPD的发生发展与机体免疫状态密切相关,多项研究试图寻找特异性强、灵敏度高的细胞与分子生物标记物,以早期诊断COPD急性加重并进行亚型区分,为COPD患者提供个体化的诊疗策略。本文综述近年来与不同表型COPD及疾病进展密切相关的免疫细胞及因子作为生物标志物的研究进展,旨在为COPD的诊断与治疗研究提供参考。

慢性阻塞性肺疾病急性加重期  /  免疫细胞  /  免疫因子  /  生物标志物

Chronic obstructive pulmonary disease (COPD) is a frequent and common disease of the respiratory system. The problem of low early diagnosis rate, low treatment compliance, and low treatment standardization has persisted in the diagnosis and treatment of COPD. Heterogeneity found in clinical practice is one of the reasons why COPD is difficult to treat. In recent years, it has been gradually recognized that the occurrence and development of COPD are closely related to the immune state of the body. At present, it become one of the hot spots in clinical and basic research that searching for specific and sensitive cell and molecular biomarkers to early diagnose acute exacerbation and subtype differentiation of COPD, which ultimately provide individual diagnosis and treatment strategies for COPD patients. This review focuses on the research progress of immunocytes and immunologic factors as biomarkers to different phenotypes and progression of COPD in recent years, providing a reference for the research on diagnosis and treatment of COPD.

acute exacerbation of chronic obstructive pulmonary disease (AECOPD)  /  immunocyte  /  immunologic factor  /  biomarker
李蕊, 肖漓. 慢性阻塞性肺疾病急性加重相关的免疫细胞及因子研究进展. 解放军医学杂志, 2023 , 48 (11) : 1353 -1358 . DOI: 10.11855/j.issn.0577-7402.1493.2023.0413
Rui Li, Li Xiao. Research progress of immunocytes and immunologic factors related to acute exacerbation of chronic obstructive pulmonary disease[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (11) : 1353 -1358 . DOI: 10.11855/j.issn.0577-7402.1493.2023.0413
慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种以持续存在呼吸道症状和气流受限为特征的常见病[1]。传统观点认为吸烟、空气污染、过敏原等引起气道慢性炎症是COPD发生的主要原因。近年相关研究指出,COPD是环境和基因相互作用的结果,且社会经济地位也是其影响因素之一[2-3]。目前对于COPD的病因及发病机制已有较为全面和深入的认识(图1),但其防治仍存在 “早期诊断率低、治疗依从性低、治疗规范性低” 等问题。近年多项研究试图寻找特异性强、灵敏度高的细胞与分子生物标记物,以早期诊断COPD急性加重并进行亚型区分,为COPD患者提供个体化的诊疗策略。本文综述近年来与不同表型COPD及疾病进展密切相关的生物标志物的研究进展,旨在为COPD的诊断与治疗研究提供参考。
COPD的病理改变主要包括小气道重塑、肺实质破坏和肺功能下降,表现为气道和肺部对有害气体、颗粒或烟雾的反应引发慢性炎症,肺部不同部位炎症细胞积聚,免疫细胞明显浸润,炎性因子分泌增加,气道管壁纤维化和不同程度的重塑,黏液纤毛清除机制受损,黏液分泌过多,导致气管和(或)肺泡异常。复杂的细胞间信号网络和局部发生的免疫反应共同驱动炎症反应的进展[4],而其中涉及的免疫细胞及分子变化是区分COPD稳定期与急性加重期(acute exacerbation of COPD,AECOPD)的物质基础。
按照2022年慢性阻塞性肺病全球倡议(Global Initiative for Chronic Obstructive Lung Disease,GOLD)标准,可将AECOPD分为轻、中、重度,分别需要不同程度的干预治疗;COPD 稳定期 (stable phase of COPD,SCOPD) 是指至少4年没有急性加重证据者[1]。近年临床发现COPD存在多种内因型和表型,逐渐认识到其异质性。COPD患者因其病因、个体易感性、免疫功能状态等存在差异,且急性加重可能表现为细菌感染、病毒感染、嗜酸性粒细胞增加、寡细胞等不同的内因型[5];根据个体差异及不同并发症组合表现为不同的临床症状,确定了7种表型,包括哮喘-COPD重叠表型、频繁急性加重表型、肺气肿型、肺功能快速下降表型、共病COPD表型、身体虚弱表型和情绪脆弱表型等[6-7],并推测应选择不同的诊疗方案。目前,临床上COPD的诊断主要基于临床症状,所以对AECOPD及其亚型的识别存在主观性和滞后性,同时AECOPD的早期诊断及其亚型的鉴别诊断对COPD诊疗方案的个体化选择尤为重要。因此,探索易检测、可靠性高的生物标记物已成为相关临床和基础研究的热点之一。
COPD作为一种慢性病,其慢性炎症微环境涉及中性粒细胞、巨噬细胞、嗜酸性粒细胞、Th1/17细胞、Tc1细胞、Th2细胞等多种炎症细胞及其分泌的炎性介质,均与COPD患者肺功能下降及病情加重密切相关,共同参与、造成相关的病理学改变。根据临床数据分析,有学者提出将COPD分为中性粒细胞性COPD和嗜酸性粒细胞性COPD。
中性粒细胞性COPD的发生机制与中性粒细胞的异常发育相关。作为免疫系统的关键组成部分,中性粒细胞占外周血白细胞的70%,细胞核呈杆状或多分叶状、细胞质呈颗粒状为其主要特征。在吸烟、有毒气体、白细胞介素-8(interleukin-8,IL-8)、肿瘤坏死因子(tumor necrosis factor,TNF)-α等因素的刺激下,中性粒细胞滞留在肺血管床并大量浸润,分泌多种蛋白酶(弹性蛋白酶、组织蛋白酶等),释放大量氧自由基,破坏机体的氧化-抗氧化动态平衡,降解周围肺组织,加剧组织损伤和气道炎症反应,导致肺泡丢失、黏液生成增多和黏膜纤毛功能障碍,最终形成中性粒细胞性COPD。
研究显示,临床症状或肺功能不同的COPD患者中性粒细胞数量和比例没有明显差异,但其免疫功能可能存在不同[8];也有临床研究报告各种表型的COPD患者(如慢性支气管炎、肺气肿甚至嗜酸性粒细胞性COPD等)均有气道中性粒细胞增多的表现,在COPD稳定期中性粒细胞处于高水平状态,急性加重期则进一步升高[9]。Dicker等[10]定量测定了COPD患者支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和血清中的中性粒细胞胞外诱捕网(NET)含量,利用流式细胞术对BALF和外周血中的中性粒细胞进行免疫功能评估,结果显示BALF中的NET与COPD严重程度密切相关(P<0.0001),且与更频繁的急性加重和微生物群多样性减少有关。中性粒细胞在COPD早期及稳定期的发生发展过程中起核心作用,因此,深入研究中性粒细胞的免疫学机制对中性粒细胞性COPD的早期诊断、病情加重的预防及患者生存质量的改善具有重要价值。
2022年GOLD更新提示,嗜酸性粒细胞对预测COPD的急性加重风险具有一定指导价值[1]。近年大量临床数据显示,血液嗜酸性粒细胞水平与COPD患者的临床症状、加重风险、住院时间和病死率密切相关,但具体的分子机制尚未完全阐明。由于COPD存在异质性,嗜酸粒性细胞的临界值及范围因患者的个体差异、临床症状而不同,使得目前嗜酸粒细胞性COPD尚无统一的定义。
嗜酸性粒细胞是由双叶细胞核和大嗜酸性细胞质颗粒组成的炎性白细胞,由骨髓中的CD34+骨髓祖细胞产生,通常数量较少,在外周血中占白细胞总数的1%~4%[11]。其突出特征是细胞质含有特殊的阳离子蛋白和颗粒,可与免疫调节介质(如细胞因子、趋化因子、生长因子及其受体等)发生相互作用;细菌、病毒感染容易导致COPD患者快速出现相应症状(如咳嗽、咳痰、喘息等),导致病情急性加重,与气道中2型介质的表达有关。基于AECOPD的异质性,大量研究尝试将嗜酸性粒细胞作为生物标志物,以不同的嗜酸性粒细胞临界值来表征嗜酸性粒细胞表型COPD患者急性加重的风险,指导临床用药,采用不同的皮质类固醇给药途径、剂量和疗程,均表现出较高的临床益处[12-13]
临床上,尝试将AECOPD患者外周血嗜酸性粒细胞计数≥3%或>200 /ml定义为嗜酸性粒细胞性COPD,此类患者的急性加重多与细菌或病毒感染有关,导致炎症增强、症状加重,加速了疾病进展,降低了患者的生活质量。Albanna等[14]的单中心回顾性研究显示,与嗜酸性粒细胞水平较低的COPD患者比较,嗜酸性粒细胞水平较高的COPD患者采用皮质类固醇治疗效果更佳,可更好地缓解症状,改善健康状况。Hastie等[15]也得出了相似的结论,吸烟史≥20包/年的COPD患者痰中嗜酸性粒细胞数量与AECOPD呈显著正相关,与肺功能、基线水平(人口统计学资料、调查问卷、定量CT、临床评估等临床资料)和支气管扩张呈显著负相关。近期多项研究报告,与非嗜酸性粒细胞性COPD患者比较,嗜酸性粒细胞性COPD患者总加重频率和住院率明显升高[16];外周血或痰中嗜酸性粒细胞数量与COPD疾病严重程度显著相关,可将其作为监测疾病进展及表型分型的生物标志物[17-18]
细胞因子是一组由多种细胞分泌的小分子蛋白或多肽,可作为信号蛋白参与细胞间的信号转导和通信,介导天然免疫和适应性免疫应答,诱导细胞凋亡,刺激造血等。细胞因子可根据其结构与功能分为IL、干扰素(interferon,IFN)、TNF、集落刺激因子和生长因子等;根据其作用特点,可分为促炎因子和抑炎因子。大量实验室及临床研究显示,在COPD患者中,炎症细胞浸润导致大量炎性介质及细胞因子释放,通过各自的促炎或抑炎作用,参与了不同表型COPD的发病及疾病进展。
IL-5可调节嗜酸性粒细胞的多种生理过程。IL-5受体(IL-5 receptor,IL-5R)由α亚基和β亚基组成,α亚基可作为结合位点,与IL-3和粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)以动态构象的方式相互作用,促进炎症反应。美泊利珠单抗是一种人源化的IgG1单克隆抗体,靶向外周血中的IL-5,可抑制IL-5与IL-5R α亚基的结合。Narendra等[19]的一项多中心Ⅲ期随机对照临床试验结果显示,与安慰剂组(n=674)比较,接受100 mg(每4周一次)美泊利单抗治疗的COPD患者的中度或重度加重的发生率降低了23%,其治疗效果优于300 mg(每4周一次)美泊利单抗。另有研究显示,抗IL-5治疗显著降低了嗜酸性粒细胞性COPD患者的年度急性加重率和严重不良事件发生率[20],提示IL-5可作为嗜酸性粒细胞性COPD潜在的治疗靶点。
IL-33属于IL-1超家族成员,由270 个氨基酸残基组成两个保守的结构域,可与受体ST2相互作用,是一种多效性免疫调节分子,主要参与2型免疫反应,其编码基因位于人类9号染色体短臂(9p24.1)[21-22]。已有研究显示,IL-33在稳定状态下可由多种细胞表达,包括内皮细胞、网状细胞、神经胶质细胞、成纤维细胞、上皮细胞、神经元和星形胶质细胞等,并定位于细胞核中;当机体受到烟草烟雾、有毒气体、过敏原等刺激后,免疫平衡受到破坏,应激或炎症状态下IL-33的表达增强[23]
近年来,IL-33广受国内外学者的关注,其在免疫学领域的作用逐步被揭示。有研究报告IL-33可通过产生自身免疫性抗体,进一步破坏COPD患者的肺泡结构,引发局部炎症和慢性进行性气道阻塞等[24]。Altman等[25]报道IL-33在肥大细胞与气道平滑肌细胞串扰中起关键作用,这两种类型的细胞均可产生IL-33,且肥大细胞产生的IL-33可激活并增加IL-13的分泌,随后在体外和体内使气道平滑肌收缩,与COPD的发病机制密切相关。Rabe等[26]用人IgG4单克隆抗体itepekimab靶向IL-33,结果显示,与安慰剂比较,尽管itepekimab治疗未达到降低COPD年度中重度急性加重率的主要目标(相对风险RR=0.81,95%CI 0.61~1.07,P=0.13),但亚组分析显示,靶向IL-33在降低急性加重频率和改善肺功能方面有潜在益处(相对风险RR=0.58,95%CI 0.39~0.85,P=0.0061)。目前,多项针对IL-33的单克隆抗体在COPD及其亚型疾病进展中的作用的临床研究正在进行,这可能为不同表型的COPD患者提供新的有效治疗方案。
IL-10作为多功能的细胞因子,可由人体多种细胞产生和分泌,以Th2细胞为主。IL-10作为一种抑炎因子,能够通过增加M2极化和减少中性粒细胞浸润,调节T、B、自然杀伤(natural killer,NK)等淋巴细胞的增殖和分化,减少炎性因子分泌,从而抑制或终止炎症反应。Silva等[27]发现,与SCOPD患者比较,AECOPD患者肺功能较差,IL-10、甘油三酯和内脏脂肪面积水平较低,IL-6水平和IL-6/IL-10比值较高。Song等[28]则提出,低水平IL-10可促进炎症反应,导致COPD严重程度加重。
已知COPD的发病机制与气道和全身炎症有关,且与多种疾病共存。Wei等[29]回顾性分析了IL-10与中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)联合检测对AECOPD合并急性肾损伤(acute kidney injury,AKI)的诊断价值,结果显示,AECOPD组、AECOPD合并AKI组与健康对照组的炎性因子IL-2、IL-10、IL-17和NGAL水平均有明显差异(P<0.01);IL-10与NGAL联合检测对AECOPD合并AKI的诊断效果更好。此外,Tang等[30]报告IL-10 在 COPD 患者中可能具有保护作用,可抑制部分趋化因子和蛋白酶的作用,减少肺实质中弹性蛋白的破坏,从而影响疾病的预后。
IL-26是由171个氨基酸残基(36 kD)组成的二聚体,由白细胞和结构细胞群产生,与IL-10具有较高的序列同源性(25%的氨基酸同一性和47%的相似性),因此被归为IL-10家族成员[31-32]。IL-26具有直接和间接的抗菌特性,可降低细胞内细菌的活力,在细胞外形成细菌和自身DNA的复合物,杀死细胞外细菌[33];还可与Toll样受体 (Toll-like receptors,TLRs)相互识别,抑制病毒复制。IL-26在气道中非常丰富,具有独特的组合模式,可介导先天和适应性免疫反应,在支气管上皮细胞、中性粒细胞中的作用更加复杂,可直接抑制促炎因子(如IL-8、TNF-α、GM-CSF和IFN)的释放。
Che等[34]的研究显示,在细菌性肺炎患者中,IL-26可抑制中性粒细胞活化,促进巨噬细胞表达IL-10,从而间接杀死细菌。Cardenas等[35]的研究显示,长期吸烟者、慢性支气管炎、SCOPD或AECOPD患者的诱导痰和BALF液中IL-26浓度增高。目前IL-26与AECOPD的相关研究尚少,从其免疫学结构特点及功能来看,有望成为AECOPD的生物标志物。
急性时相蛋白(acute-phase protein,APP)与急性期全身炎症和免疫反应相关,是机体在病毒或细菌感染、梗阻等所致炎症反应的急性阶段发生血浆浓度改变,以及快速响应机体代谢反应、免疫状态改变的急性时相反应蛋白,通常在2~5 d达到峰值。大量研究显示,APP是COPD和AECOPD发病机制的关键参与者,在AECOPD阶段的表达水平高于康复阶段。
CRP是APP的一种,是组织损伤和全身炎症反应的敏感指标[36]。临床数据分析显示,感染会加速COPD患者的疾病进展,与基线水平比较,细菌感染型AECOPD的CRP水平明显升高;尽管CRP不是疾病特异性的,但它可以辅助临床决策以指导抗菌药物的使用[37]
Prins等[38]的研究显示,依据血清CRP水平(临界值50 mg/L)指导临床抗生素治疗,可显著减少抗生素的使用剂量,有利于降低细菌耐药性,且没有观察到CRP指导策略对治疗失败、住院时间和不良反应的负面影响。Daniels等[39]比较了降钙素原(procalcitonin,PCT)和血清CRP对细菌感染型COPD患者急性加重的预测价值,认为血清 CRP 可更好地反映下气道的细菌感染,且其检测成本低于PCT,更适合指导细菌感染型COPD诊疗策略的选择[40]
FIB属于急性期可溶性血浆糖蛋白,主要在肝脏中由凝血酶在凝血过程中转化形成,是组织损伤、炎症和纤维化的主要调节剂。FIB水平增高与COPD发病率、住院率和全因死亡率增高相关,且与COPD的严重程度有关。美国食品药品监督管理局已批准将FIB作为COPD严重程度的生物标志物。
Ingebrigtsen等[41]对6857例COPD患者进行了FGB-455(rs1800790,G>A)和 FGB-448(rs4220,G>A)基因分型,并检测血浆FIB水平,结果显示FIB水平增高与COPD恶化风险增加相关[HR=1.14(1.07~1.22),P<0.001]。Hyun等[42]以FIB水平>3.5 g/L和嗜酸性粒细胞百分比>2%为分组依据,研究COPD患者临床表型与血浆FIB水平和外周血嗜酸性粒细胞计数的相关性,结果显示,在370例COPD患者中,FIB组和嗜酸性粒细胞组气流受限更严重,并发症更多,COPD严重程度指数更高;FIB和嗜酸性粒细胞均高的COPD患者重度加重率(0.29/年)和总加重率(中度加重率和重度加重率)(0.42/年)显著高于其他三组。
AAT是一种由394个氨基酸残基组成的52 kD的糖蛋白,主要由中性粒细胞、巨噬细胞、肝细胞产生,可作为丝氨酸蛋白酶抑制剂抑制NE和PR3等蛋白酶的水解作用,为肺组织提供重要保护,也具有免疫调节和抗微生物活性等非蛋白水解功能,可抑制感染和炎症的发生[43]
大量研究显示,AAT缺乏症(AATD)患者早年患COPD的易感性增加,尤其是肺气肿表型的COPD[44]。氧化修饰AAT(oxidized alpha-1-antitrypsin,OxyAAT)可降低其抑制剂活性和对肺组织的保护作用。Topic等[45]的研究显示,与不吸烟的健康人(P=0.030)比较,吸烟或不吸烟COPD组的OxyAAT水平均显著增高(P=0.009),且患有严重和非常严重COPD的吸烟者组OxyAAT水平最高;与吸烟或不吸烟的健康对照组比较,疾病严重程度相同的不吸烟(P=0.038)和吸烟(P=0.022)的COPD患者血清OxyAAT水平均升高;COPD吸烟者和对照组吸烟者之间的差异不显著(P=0.063)。总之,血清OxyAAT水平可能是评估吸烟对COPD发病和严重程度影响的潜在生物标志物。此外,OxyAAT作为预后生物标志物有可能用于评估抗氧化治疗对肺气肿型COPD的有效性。
综上,新的观点认为COPD亚型的鉴别对于临床诊治尤为重要,如尝试将COPD分为中性粒细胞性COPD和嗜酸性粒细胞性COPD。COPD亚型的鉴别尚待进一步探讨,包括病因、并发症、易感基因和免疫功能状态等多个方面。基础和临床研究显示,COPD患者的致病类型和临床表型存在差异性,涉及中性粒细胞、嗜酸性粒细胞、淋巴细胞、巨噬细胞等多种免疫细胞及细胞因子,如IL-1β、IL-5、IL-6、IL-8、IL-17、TNF-α、INF-γ等。动态监测免疫细胞、细胞因子等的水平对AECOPD的早期诊断及其亚型鉴定有重要价值,也有助于判断COPD的进展和预后,具有很好的临床应用前景。因此,探索特异性强且便于检测的细胞与分子标志物来判定AECOPD 亚型及疾病进展是值得进一步研究的方向。然而,使用外周血生物标志物存在一定的局限性,易受到多种因素影响,如患者身体状况、服用药物、感染等。我们建议:一方面应探索不同亚型COPD患者外周血细胞与分子水平的变化特点,这需要开展大样本量的多中心队列研究;另一方面,应围绕相关的免疫细胞和分子,探究COPD发病及加重的机制,以寻找更为有效的COPD治疗策略。
  • 首都卫生发展科研自主创新专项(2022-2-5092)
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2023年第48卷第11期
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doi: 10.11855/j.issn.0577-7402.1493.2023.0413
  • 接收时间:2022-07-07
  • 首发时间:2025-11-24
  • 出版时间:2023-11-28
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  • 收稿日期:2022-07-07
  • 录用日期:2022-11-05
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Capital Fund for Health Improvement and Independent Innovation Research(2022-2-5092)
首都卫生发展科研自主创新专项(2022-2-5092)
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    1河北北方学院研究生学院,河北张家口 075000
    2解放军总医院第八医学中心呼吸与危重症医学部研究所/北京市器官移植与免疫调节重点实验室,北京 100091

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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