炎症反应在慢性阻塞性肺疾病伴发肺动脉高压中的作用

炎症反应在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)伴发肺动脉高压的发生、发展中起着重要作用.气道存在炎症时,激活的炎症细胞释放肿瘤坏死因子a(TNF-α)、白介素6(IL-6)和IL-8等多种细胞因子,共同参与气道壁、肺泡壁的结构破坏和重塑.这些气道炎症反应不仅影响已存在缺氧的COPD伴肺动脉高压患者,也可影响尚不存在缺氧的COPD伴肺动脉高压患者,可能是早期COPD患者肺动脉重塑及血流动力学改变的始动环节.     

炎症在慢性阻塞性肺疾病相关肺动脉高压发病机制中的作用的研究进展

慢性阻塞性肺疾病(COPD)是以气道、肺实质、肺血管慢性炎症为主要特征的慢性肺疾病.肺动脉高压是COPD的主要并发症.近年来新的研究表明,COPD相关肺动脉高压的主要发病机制除缺氧外,炎症介质如白介素16、C反应蛋白、肿瘤坏死因子α、内皮素1等及炎症细胞如中性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等也起重要作用.     

白介素32在气道炎症反应中的研究进展

在哮喘和慢性阻塞性肺疾病中,气道炎症反应始终贯穿疾病的发生、发展及转归.目前已发现有众多细胞及因子参与气道炎症反应,而白介素32作为一种新发现的细胞因子,很多文献证明其在炎症反应中有不可取代的作用.白介素32主要存在于自然杀伤细胞、T细胞、上皮细胞及外周血的单核细胞中,在自然免疫及特殊免疫中均有重要地位.在炎症反应中,白介素32可诱导某些因子的活性,如白介素类、肿瘤坏死因子α、核因子、促分裂原活化蛋白激酶及各种趋化因子,形成炎症级联式反应,造成气道局部的炎症,甚至引起全身性炎症反应.本文对白介素32在气道炎症中的作用作一综述.     

炎症反应与慢性阻塞性肺疾病肺功能分级

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是呼吸系统最常见的疾病之一,以气道、肺实质和肺血管的慢性炎症为特征,多种炎症细胞、细胞因子及炎性介质参与其发生发展.COPD发病率和致死率均较高,在未来数十年内其发病率仍将继续上升.因此,探索该病有效的治疗方法势在必行.本文就炎症反应与COPD肺功能分级关系作一综述,揭示炎症反应对COPD患者肺功能的影响.     

白介素8与慢性阻塞性肺疾病

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是呼吸系统的常见病、多发病,COPD患病人数多、病死率高,近年来发病率呈明显上升的趋势.COPD的确切发病机制尚不完全清楚,目前认为炎症是COPD发生发展的主要机制.白介素8(IL-8)是主要的炎症介质之一,在COPD患者多种因素可以导致其明显增高,IL-8有强力的中性粒细胞、T细胞及嗜碱粒细胞趋化作用,并可激活中性粒细胞,产生中性粒细胞反应,破坏肺泡,产生多种炎症效应.对IL-8的干预可能影响COPD的炎症过程.     

慢性阻塞性肺疾病与白介素-4、8和干扰素-γ的关系

以细胞毒性T细胞、巨噬细胞及中性粒细胞为主的气道壁及肺泡隔的慢性炎症和进行性发展的气流阻塞是慢性阻塞性肺疾病 (COPD)的两大特点。其慢性炎症由多种细胞因子尤其是白介素 8(IL 8)、干扰素 γ(IFN γ)等介导。IL 8在COPD的发病过程中贯穿始终 ,在其气道炎症的发生发展过程以及气流阻塞中起着至关重要的作用。IFN γ与COPD的关系也日益受到重视 ,有可能是连接COPD发病机制中细胞分子生物学和蛋白酶 /抗蛋白酶系统失衡的桥梁     

趋化因子与慢性阻塞性肺疾病

慢性阻塞性肺疾病（COPD）是以慢性气流受限为特征的缓慢进展、渐进加重的肺部疾病。气道慢性炎症，特别是中小气道炎症是其主要病变特征。COPD气道慢性炎症是由复杂的炎性细胞及其分泌的细胞因子相互诱导、相互调节而发生发展的，最终导致气道结构的重构和气流阻塞的形成，在COPD发病中起着十分重要的作用。而炎性细胞趋肺的过程又有赖于多种趋化因子的参与方可完成。很多学者认为趋化因子在COPD患者气道炎症中起了关键性的作用。近年来，随着对COPD气道炎症特点研究的逐渐深入，趋化因子日益成为COPD研究的热点之一。本文就趋化因子在COPD发病中的作用机制及其临床应用价值作简要综述。     

微粒在慢性气道炎症性疾病中的作用

研究表明微粒作为细胞间信号转导的载体,在多种疾病中起着重要作用。它通过对细胞的内分泌、分子信号转导、物质合成等生物功能的调节而影响组织的损伤、修复,参与疾病的发生、发展。在病理状态下,微粒数量增多、内容物发生改变,影响靶细胞的物质代谢、能量代谢,导致靶细胞结构、功能改变,从而引起组织、器官结构功能改变,导致疾病发生。而慢性气道炎症性疾病是以气道阻塞、气道重塑为主要特征的疾病,气道的慢性炎症是其基本特点,越来越多的证据表明微粒与气道慢性炎症性疾病的发生、发展有着密切联系,在气道上皮的损伤与修复过程中起着关键性作用。该综述将阐述微粒在支气管哮喘、COPD 等疾病进程中的作用,以期通过对微粒产生及作用机制的了解,帮助寻找疾病诊疗的新策略。     

慢性阻塞性肺疾病与白介素—4、8和干扰素—γ的关系

以细胞毒性T细胞，巨噬细胞及中性粒细胞为主的气道壁及肺泡隔的慢性炎症和进行性发展的气流阻塞是慢性阻塞性肺疾病（COPD）的两大特点，其慢性炎症由多种细胞因子尤其是白介素-8（IL-8），干扰素-γ（IFN-γ）等介导，IL-8在COPD的发病过程中贯穿始终，在其气道炎症的发生发展过程以及气流阻塞中起着至关重要的作用，IFN-γ与COPD的关系也日益受到重视，有可能是连接COPD发病机制中细胞分子生物学和蛋白酶/抗蛋白酶系统失衡的桥梁。     

炎性因子在慢性阻塞性肺疾病气道炎症中的作用

COPD是一种以气道慢性炎症为特征之一的慢性呼吸系统疾病,气道炎性反应在COPD占有重要作用。炎性细胞因子是机体内最重要的一类细胞因子,多种炎性细胞因子参与气道炎症的病理生理机制,对肺组织和支气管产生损害,并发肺外效应。在COPD的自然病程中存在炎性细胞因子网络系统,调控COPD的气道炎症的发生发展。     

IL-1β、IL-6及TNF-α在慢性阻塞性肺疾病中的作用及研究进展

慢性阻塞性肺疾病目前已经成为全球第3大死因的慢性疾病,疾病病程长,经济负担重。现已发现多种致病原因,在临床患者的调查研究中发现,慢性阻塞性肺疾病多与炎症反应相关。本文主要叙述白细胞介素1β、白细胞介素6及肿瘤坏死因子α 3种慢性阻塞性肺疾病中相关的炎症因子,以及这些炎症因子引起的不同病理改变。因此,对炎症因子的作用机制...     

Role of viruses in exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.     

Impact of sputum bacteria on airway inflammation and health status in clinical stable COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The aim of this study was to determine the impact of sputum potentially pathogenic microorganisms (PPMs) on bronchial airway inflammation, health status and plasma fibrinogen levels in subjects with moderate-to-severe COPD during the clinical stable state. Sputum total cell and neutrophil counts, supernatant interleukin-8, leukotriene B4, tumour necrosis factor-alpha and neutrophil elastase levels, neutrophil chemotaxis and plasma fibrinogen levels were estimated. Health status was determined using the St George's Respiratory Questionnaire and the 36-item Short-Form Health Survey questionnaire. Twenty-seven (40%) subjects had PPMs and 40 (60%) non-PPMs in their sputum. Both groups were of similar age, body mass index, smoking history and lung function. The PPMs group showed significantly higher levels of interleukin-8, leukotriene B4, tumour necrosis factor-a, neutrophil elastase and increased neutrophil chemotaxis. They also exhibited worse health status and raised plasma fibrinogen levels compared to the non-PPMs group. In conclusion, subjects with clinically stable moderate-to-severe chronic obstructive pulmonary disease who had potentially pathogenic microorganisms in their sputum demonstrated an exaggerated airway inflammatory response, poorer health status and increased plasma fibrinogen levels than those who had nonpotentially pathogenic microorganisms.     

Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation

RATIONALE: Emphysema is one component of chronic obstructive pulmonary disease (COPD), a respiratory disease currently increasing in prevalence worldwide. The mainstay therapy adopted to treat patients with COPD is glucocorticoids; unfortunately, this treatment has limited impact on disease symptoms or underlying airway inflammation. OBJECTIVE: There is an urgent need to develop therapies that modify both the underlying inflammation, thought to be involved in disease progression, and the structural changes in the emphysematous lung. METHODS: We have characterized an elastase-driven model of experimental emphysema in the rat that demonstrates COPD-like airway inflammation and determined the impact of a clinically relevant glucocorticoid. MEASUREMENTS AND MAIN RESULTS: We observed an increase in lung neutrophils, lymphomononuclear cells, mucus production, and inflammatory cytokines. Also present were increases in average air space area, which are associated with emphysema-like changes in lung function, such as increased residual volume and decreased flow; these increases in area were maintained for up to 10 weeks. In addition, we observed that elastase-induced airway neutrophilia is steroid resistant. Interestingly, the inflammation observed after elastase administration was found to be temporally associated with a lack of nuclear factor-kappaB pathway activation. This apparent nuclear factor-kappaB-independent inflammation may explain why treatment with a glucocorticoid was ineffective in this preclinical model and could suggest parallels in the steroid-resistant human disease. CONCLUSION: We believe that this model, in addition to its suitability for testing therapies that may modify existing emphysema, could be useful in the search for new therapies to reduce the steroid-resistant airway inflammation evident in COPD.     

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.     

Cytokine-mediated xanthine oxidase upregulation in chronic obstructive pulmonary disease's airways

Reactive oxygen species have been reported to be involved in the airway inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to quantify the activity of xanthine oxidase (XO), which generates a potent radical superoxide anion in COPD airways. Thirteen stable COPD patients and 10 healthy subjects participated in this study. We collected the epithelial lining fluid using a newly developed microsampling technique, and quantified of cytokines responsible for the XO gene upregulation. The XO activity was significantly increased in COPD patients compared with that in healthy subjects. A significant negative correlation was found between the XO activity and the %FEV1 values. The level of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in COPD patients was significantly higher than that in healthy subjects. Both the amount of tumor necrosis factor-alpha and interleukin-1beta were significantly correlated with the degree of XO activity. These results suggest that the XO activity is increased in COPD airways, possibly due to its gene upregulation by proinflammatory cytokines. Because the XO activity was significantly correlated with the degree of airway obstruction, these cytokine-XO production pathways may play a key role in the inflammation of COPD.     

COPD患者糖皮质激素不敏感的发生机制和应对策略研究进展

COPD 是常见的慢性气道炎症性疾病,持续气道炎症导致不完全可逆的气流受限和肺结构破坏,引起肺功能进行性下降。尽管目前 COPD 的诊断和治疗已有很大的进步,但由于大气污染加重、烟雾和臭氧暴露增加, COPD 的发病率和病死率在全球仍居高不下。糖皮质激素(glucocorticoid,GC)在哮喘等常见慢性炎症疾病和自身免疫性疾病中的治疗有效性已被临床实践证实,但大量实验研究表明,GC 在 COPD 治疗中疗效欠佳,出现 GC 不敏感现象,因此关于 COPD 患者 GC 不敏感的机制和对策研究意义重大。本文就 COPD 患者气道炎症特征、GC 不敏感发生机制、改善 GC 不敏感的应对策略进行综述。     

Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD

STUDY OBJECTIVE: The upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PARTICIPANTS: Forty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status. MEASUREMENTS: Serum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects. RESULTS: COPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response. CONCLUSIONS: COPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.