State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?
State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?
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DOI：
10.1186/1465-9921-4-8
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发表时间：
2003
影响因子：
5.8
通讯作者：
Davis PB
中科院分区：
文献类型：
--
作者：
Chmiel JF;Davis PB
囊性纤维化(CF)是以呼吸道阻塞、慢性细菌感染和过度炎症反应为特征的肺部疾病，是导致大部分发病率和死亡率的原因。在生命的早期，CF患者会感染有限的细菌，特别是铜绿假单胞菌。新的数据表明，睫状液深度的减少和粘液的异常水合，阻碍了粘液纤毛的清除，导致了最初的感染。抗菌分子一氧化氮的产生减少，CF呼吸道上皮细胞上细菌结合部位(如asialo GM-1)增加，以及细菌对呼吸道微环境的适应，包括产生毒力因子和组织成生物膜的能力，导致对初始细菌感染的易感性。一旦患者被感染，肺中过度活跃的炎症反应可能会导致宿主无法根除感染。作为对IL-8和白三烯B4产生增加的反应，中性粒细胞渗透到肺中，在那里它们释放介质，如弹性蛋白酶，进一步抑制宿主防御，削弱吞噬细胞功能，损害粘液纤毛清除，并破坏气道壁结构。这些事件的结合有利于细菌在呼吸道中的持续存在。在发现治愈方法之前，对解除梗阻、控制感染和减轻炎症的治疗方法的进一步研究为限制对宿主组织的损害和延长生存提供了最大的希望。
Cystic Fibrosis (CF) lung disease, which is characterized by airway obstruction, chronic bacterial infection, and an excessive inflammatory response, is responsible for most of the morbidity and mortality. Early in life, CF patients become infected with a limited spectrum of bacteria, especially P. aeruginosa. New data now indicate that decreased depth of periciliary fluid and abnormal hydration of mucus, which impede mucociliary clearance, contribute to initial infection. Diminished production of the antibacterial molecule nitric oxide, increased bacterial binding sites (e.g., asialo GM-1) on CF airway epithelial cells, and adaptations made by the bacteria to the airway microenvironment, including the production of virulence factors and the ability to organize into a biofilm, contribute to susceptibility to initial bacterial infection. Once the patient is infected, an overzealous inflammatory response in the CF lung likely contributes to the host's inability to eradicate infection. In response to increased IL-8 and leukotriene B4 production, neutrophils infiltrate the lung where they release mediators, such as elastase, that further inhibit host defenses, cripple opsonophagocytosis, impair mucociliary clearance, and damage airway wall architecture. The combination of these events favors the persistence of bacteria in the airway. Until a cure is discovered, further investigations into therapies that relieve obstruction, control infection, and attenuate inflammation offer the best hope of limiting damage to host tissues and prolonging survival.
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影响因子：
56.9
作者：
Ernst, RK;Yi, EC;Miller, SI
通讯作者：
Miller, SI
影响因子：
3.1
作者：
Arora, SK;Ritchings, BW;Ramphal, R
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Ramphal, R
DOI：
10.1164/ajrccm.156.4.96-11058
发表时间：
1997-10-01
影响因子：
24.7
作者：
Armstrong, DS;Grimwood, K;Phelan, PD
通讯作者：
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影响因子：
168.9
作者：
Equi, A;Balfour-Lynn, IM;Rosenthal, M
通讯作者：
Rosenthal, M
影响因子：
7.2
作者：
DEMKO, CA;BYARD, PJ;DAVIS, PB
通讯作者：
DAVIS, PB