辨证治疗AECOPD呼吸衰竭疗效评价及对单核细胞Toll样受体和外周血细胞因子的影响
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摘要
目的
慢性阻塞性肺疾病急性加重(AECOPD)呼吸衰竭是导致严重危害公众健康的重大疾病,致死率高,经济负担重。中医药干预AECOPD呼吸衰竭具有一定的疗效和优势,但缺乏系统研究,机制探讨不深入。炎性细胞介导的炎症反应在其中起着重要的作用,Toll样受体(Toll like receptors, TLRs)信号途径在COPD发病机制中的作用受到广泛关注,但对TLR在COPD患者体内实际作用和表达情况的研究较少。本文目的在于从临床方面进行中医辨证治疗AECOPD呼吸衰竭的临床疗效评价,并从单核细胞免疫功能、外周血细胞因子等方面探索中医辨证治疗方案治疗AECOPD呼吸衰竭的机制。
对象与方法
按照随机对照原则,将AECOPD呼吸衰竭患者分为试验组(辨证治疗+西医常规治疗)和对照组(西医常规治疗),试验组入选52例,对照组52例,试验组在常规治疗基础上进行辨证治疗,评价病死率、气管插管率、撤机率、VAP发生率,于治疗第0,4,7,14天,评测临床症状体征积分,APACHEⅡ评分,血常规,血气分析,MMRC评分等；应用流式细胞仪全血免疫荧光直标法检测单核细胞TLR4蛋白和外周血中T细胞亚群CD4+.CD8+及其比值；应用RT-PCR去测定单核细胞TLR4mRNA、CD 14mRNA、NF-κBp65mRNA水平；酶连免疫吸附法(ELISA)测定外周血CRP,细胞因子β-EP.IL-lb. IL-6、IL-8、TNF-α、IFN-y,安全性评价采用报告表记录患者不良反应,并观察治疗前后血常规,尿常规,大便常规,肝肾功能,心电图进行评价。
结果
本项目共完成104例病例,其中试验组52例,对照组52例,试验组脱落3例,对照组脱落4例,临床观察结果表明：
1试验组死亡2例(3.85%),气管插管8例(15.38%),拔管撤机6例(75.0%),与对照组的3例(5.77%),11例(21.15%),4例(36.36%)比较无统计学意义。试验组患者中2例出现机械通气相关肺炎(VAP),与对照组8例比较差异有统计学意义(P=0.0397)。
2试验组治疗后症状体征总积分和症状评分明显低,与对照组差异有统计学意义(P<0.05),体征总积分与对照组比较无统计学意义(F=0.989,P=-0.322)；咳嗽、咯痰、喘息、气短、乏力、心悸、烦燥、腹胀、浮肿等单项积分试验组显著低于对照组(P＜0.05),胸闷、汗出、头痛、语言错乱、食少、哮鸣音、紫绀、精神状态积分两组间差异无统计学意义(P>0.05)。
3两组治疗后APACHEⅡ评分均较治疗前降低,试验组下降幅度较对照组明显,差异有统计学意义(F=4.325,P=0.040)。
4两组治疗后白细胞总数及中性粒细胞百分比渐下降,组间比较(P=0.336；P=0.517)无显著差异。
5试验组治疗后血氧分压与对照组比升高显著(P=0.002)；试验组二氧化碳降低与对照组比较差异无统计学意义(P=0.988)。
6治疗后试验组CD4~+、CD4~+/CD8+轻度上升,CD8+与治疗前比较明显回升(P＜0.01)。对照组CD4~+,CD8+台疗后较治疗前轻度升高,CD4~+/CD8+下降,无统计学差异(P＞0.05)。各指标试验组与对照组差异无统计学意义(P>0.05)。
7两组治疗后MMRC评分均较治疗前下降,试验组呼吸困难评分下降与对照组差异有统计学意义(P=0.007)。
8 AECOPD呼吸衰竭患者外周血单核细胞CD14~+低于正常人组,与稳定期患者比较显著下降(P<0.05)；AECOPD呼吸衰竭患者CD14蛋白(荧光强度)表达低于稳定期组和正常人组,差异无统计学意义(P>0.05)；AECOPD呼吸衰竭患者TLR4阳性细胞相对百分率高于稳定期组和正常人组,两组与正常人组间差异有统计学意义(P<0.05)；AECOPD呼吸衰竭患者TLR4平均荧光强度高于稳定期组和正常人组,各组间差异无统计学意义(P>0.05)。
9治疗后试验组CD14阳性细胞数与治疗前比较轻度上升(P>0.05),CD14蛋白(荧光强度)轻度下降(P＞0.05),与对照组比较差异无统计学意义(P>0.05)；治疗后试验组TLR4阳性细胞数和TLR4蛋白(荧光强度)轻度下降(P>0.05),与对照组比较差异无统计学意义(P>0.05)。
10治疗后试验组血单核细胞TLR4mRNA.CD14mRNA. NF-κBp65mRNA水平均较对照组下降趋势显著,其中CD14mRNA与对照组比较有显著差异(P=0.020)。
11治疗后试验组血清CRP下降明显,与对照组有显著差异(P=0.045)。
12治疗后试验组血清β-EP, IL-1b、IL-6、IL-8、TNF-α水平均出现下降,对照组大都变化不明显或持续上升,试验组与对照组在IL-8(P>=0.047)、TNF-α(P=0.032)比较有显著性差异。试验组IFN-γ轻度上升,对照组第7天上升,第14天下降到治疗前水平，两组比较无显著差异(P>0.05)。
13安全性评价方面,辨证治疗AECOPD安全有效,未出现严重不良反应,最常见的不良事件是腹泻,腹胀。两组间无显著差异(P>0.05)。
结论
1辨证治疗AECOPD呼吸衰竭临床效果显著。能够降低咳嗽、咯痰、喘息、气短、乏力、心悸、烦燥、腹胀等症状积分,降低浮肿的体征积分；提高动脉血氧分压(PaO2)；降低呼吸困难评分(MMRC);降低APACHEⅡ评分。
2外周血单核细胞免疫功能与AECOPD呼吸衰竭的发病有关。
3中医辨证治疗AECOPD呼吸衰竭的机制可能与下调单核细胞表面TLR4的表达,减轻TLR4和NF-kB介导的炎症反应有关。CRP、IL-8、TNF-α水平与病情严重程度有关,可能可作为判断AECOPD病情严重程度的候选指标。
4辨证治疗在减少VAP发生率方面有一定优势；在插管率、拔管率方面显示了较好的趋势,但无统计学意义,可能与样本量较少有关；在降低病死率方面与对照组比较无显著差异。
Objective
chronic obstructive pulmonary disease (COPD) combined with acute respiratory failure are key drivers of morbidity and mortality, which results in an economic and social burden that is both substantial and increasing. It is reported that treatment with Traditional Chinese Medicine(TCM) may do some benefit to the disease, but the quality of evidence is poor, and mechanism about TCM treatment is not so clear. Inflamation induced by inflammatory cells appears to be amplified in patients who develop COPD. TLRs (Toll-like receptors) comprise a family of proteins whose function is principally to facilitate the detection of, and response to pathogens, viruses, bacteria and fungi can all activate TLR signaling pathway, and these signals have important roles in the activation of COPD host defence. But most of our knowledge of TLRs has emerged from studies of animals. The contribution of TLRs function to human COPD is less advanced.
To investigate clinical therapeutic effect of patients with AECOPD and respiratory failure by treatment of syndromes differentiation of TCM, and the pathogenesis of treatment of syndromes differentiation of TCM, their cellular and molecular mechanisms, and how these underlie physiologic abnormalities and symptoms characteristic of the disease.
Methods
Of a total of 104 patients, we randomly assigned 52 to the control group and 52 to the experimental group. The control group were treated by conventional medicine treatment, the experimental group were treated by TCM besides conventional medicine treatment. The primary efficacy endpoint was mortality, intubation and extubation rate and VAP rate. Secondary endpoints included health status measured by symptomes scores, APACHEⅡscores, blood rutine examination, blood gas analysis and MMRC scores (measured the 0,4,7,14 day after study medication). The expression of TLR4 surface molecules on human CD 14~+ monocytes was assessed using FACS analysis by flow cytometry (measured the 0 and 14 day), so is CD4~+、CD8+T cells. The TLR4mRNA、CD14mRNA、NF-κBp65 mRNA of human CD 14~+ monocytes was assessed by Reverse Transcriptase Polymerase Chain Reaction method(measured the 0,7,14 day)..β-EP、IL-1b、IL-6、IL-8、TNF-α、IFN-γin peripheral blood of patients were assessed by means of enzyme linked immunosorbent assay method(measured the 0,7,14 day). Safety was assessed by documenting all adverse events. Routine examination of blood, urine, stools, liver and renal function, electrocardiograms were performed at days 0 and 14.
Results
Of a total of 104 patients,52 were assigned to the control group and 52 to the experimental group.3 in experimental group and 4 in the control group drop out.
1 2(3.85%) of patients in experimental group died compared with 3 (5.77%) in the control group (P=0.6467).8 (15.38%) of patients in experimental group intubated compared with 11 (21.15%) in the control group(P=0.6118).6(75.0%) extubated in experimental group compared with 4(36.36%) in the control group(P=0.0959). More ventilator-associated pneumonia were reported in the control group relative to experimental group (P=0.0397).
2 The clinical status in experimental groups decreased significantly compared to the control group during the study period(P=0.041), and so was the symptomes scores(P=0.016). There was no significant difference about scores of signs between the two groups (P=0.322).Score of the independent item such as cough, expectoration, gasping, short breath, lack of power, palpitation, upset, abdominal distension and edema decreased significantly compared to the control group during the study period. Dyspnea, sweating, headache, paraphasia, anorexia, wheezing, cyanosis and mental status scores of TCM patients showed no difference to the control group.
3 APACHEⅡscore were decreased in both the two groups at days 14, it was lower in the experimental treatment group than the control group during the study period (P=0.040)
4 Total white cell count in peripheral blood and the neutrophil percentage decreased in the two groups at days 14, it was lower in the experimental treatment group during the study period, there was no major difference between the two groups(P=0.336, P=0.517).
5 Arterial oxygen tension(PaO_2) increased in both the two groups during the study period, it was higher in the experimental treatment group, and there was significant difference between the two groups(P=0.002). Partial pressure of carbon dioxide (PaCO2) in the experimental treatment group showed no significant difference to the conventional treated patients (P=0.988).
6 CD4(+) T cells and ratio of CD4~+/CD8~+ increased in AECOPD patients, CD8(+) T cells in experimental group increased over the study period(P<0.01), CD4(+), CD8(+) T cells in control group increased too ratio of CD4~+/CD8+ decreaced. there were no significant difference between the two groups(P>0.05).
7 The MMRC dyspnoea scale scores decreased in both group during the study period (P=0.000), it was lower in the experimental treatment group than the control group during the study period (P=0.007)
8 CD 14 on AECOPD patients peripheral blood monouclear cell were little lower compared to normal using FACS analysis, and decreased significantly compared to the stable COPD patients (P<0.05). the CD 14 X-mean expressed elevated in stable COPD patients and decreased in severe AECOPD patients, there were no significant difference between them. TLR4 was elevated in stable and AECOPD patients as compared to normal ones, there was significant difference between COPD patients and normals (P<0.05). TLR4 X-mean expressed elevated in stable and AECOPD patients, there was no significant difference between three groups.
9 CD 14 expression were elevated in the experimental(P>0.05) and down-regulated in control group(P>0.05) after treatment. CD14 X-mean expression were not changed much in both groups, and there was no significant difference between them. Expression of TLR4 on monouclear cell were similar in the two groups, and reduced over the treatment period, there was no significant difference as compared to before treatment. TLR4 X-mean expression down-regulated in experimental group and control group, there was no significant difference as compared to before treatment and between them(P>0.05).
10 Compared with the control group, TLR4mRNA、CD14mRNA. NF-κBp65mRNA in monocyte of the experimental group decreased after treatment, The expression levels of CD14mRNA decreased significantly(P=0.020)
11 C-reactive protein in serum was reduced in both the two groups after treatment, CRP in the experimental group reduced more compare to the control group (P=0.045).
12 The level ofβ-EP、IL-1b、IL-6、IL-8、TNF-αin serum was reduced in the experimental group after treatment, all the cytokines in the experimental group reduced more than the control group, especially the IL-8 (P=0.047) and TNF-α(P=0.032). IFN-γin serum was increased gently in the experimental group, but no more than the control group (P<0.05).
13 Safety evaluation, treatment by syndromes differentiation of TCM is safe and effective, no severe adverse reaction reported. Only a few reporting some adverse event, the most frequent of which were diarrhea and abdominal distension.
Conclusion
1 Treatment by syndromes differentiation of TCM to patients with COPD exacerbations and respiratory failure have obvious therapeutic effect. It can relieve clinical symptoms, decrease APACHEⅡscore and the MMRC dyspnea scale outcome. The mechanism of action may related to the following reason.
2 CD 14 and TLR4 expression on monouclear cell increaced in patients with AECOPD and respiratory failure, so peripheral blood monouclear cell may related to the disease.
3 TCM may have the role cf inhibiting activation of TLR4 and nuclear factor-kappaB signaling pathway on peripheral blood monoeytes in patients with AECOPD with respiratory failure, which may associated with reduced cytokine concentration, then relieving the sytemic inflammatory responses. The concentration of CRP、IL-8、TNF-αrelevant to severity of the disease, and maybe it can be take as a biomarker for AECOPD.
4 The experimental group have some advantage in VAP rate. The experimental group have less in intubation and more extubation patients, given more sample, it might be a difference conclusion. There were no significant difference in death rate in the two groups,
慢性阻塞性肺疾病急性加重(AECOPD)呼吸衰竭是导致严重危害公众健康的重大疾病,致死率高,经济负担重。中医药干预AECOPD呼吸衰竭具有一定的疗效和优势,但缺乏系统研究,机制探讨不深入。炎性细胞介导的炎症反应在其中起着重要的作用,Toll样受体(Toll like receptors, TLRs)信号途径在COPD发病机制中的作用受到广泛关注,但对TLR在COPD患者体内实际作用和表达情况的研究较少。本文目的在于从临床方面进行中医辨证治疗AECOPD呼吸衰竭的临床疗效评价,并从单核细胞免疫功能、外周血细胞因子等方面探索中医辨证治疗方案治疗AECOPD呼吸衰竭的机制。
对象与方法
按照随机对照原则,将AECOPD呼吸衰竭患者分为试验组(辨证治疗+西医常规治疗)和对照组(西医常规治疗),试验组入选52例,对照组52例,试验组在常规治疗基础上进行辨证治疗,评价病死率、气管插管率、撤机率、VAP发生率,于治疗第0,4,7,14天,评测临床症状体征积分,APACHEⅡ评分,血常规,血气分析,MMRC评分等；应用流式细胞仪全血免疫荧光直标法检测单核细胞TLR4蛋白和外周血中T细胞亚群CD4+.CD8+及其比值；应用RT-PCR去测定单核细胞TLR4mRNA、CD 14mRNA、NF-κBp65mRNA水平；酶连免疫吸附法(ELISA)测定外周血CRP,细胞因子β-EP.IL-lb. IL-6、IL-8、TNF-α、IFN-y,安全性评价采用报告表记录患者不良反应,并观察治疗前后血常规,尿常规,大便常规,肝肾功能,心电图进行评价。
结果
本项目共完成104例病例,其中试验组52例,对照组52例,试验组脱落3例,对照组脱落4例,临床观察结果表明：
1试验组死亡2例(3.85%),气管插管8例(15.38%),拔管撤机6例(75.0%),与对照组的3例(5.77%),11例(21.15%),4例(36.36%)比较无统计学意义。试验组患者中2例出现机械通气相关肺炎(VAP),与对照组8例比较差异有统计学意义(P=0.0397)。
2试验组治疗后症状体征总积分和症状评分明显低,与对照组差异有统计学意义(P<0.05),体征总积分与对照组比较无统计学意义(F=0.989,P=-0.322)；咳嗽、咯痰、喘息、气短、乏力、心悸、烦燥、腹胀、浮肿等单项积分试验组显著低于对照组(P＜0.05),胸闷、汗出、头痛、语言错乱、食少、哮鸣音、紫绀、精神状态积分两组间差异无统计学意义(P>0.05)。
3两组治疗后APACHEⅡ评分均较治疗前降低,试验组下降幅度较对照组明显,差异有统计学意义(F=4.325,P=0.040)。
4两组治疗后白细胞总数及中性粒细胞百分比渐下降,组间比较(P=0.336；P=0.517)无显著差异。
5试验组治疗后血氧分压与对照组比升高显著(P=0.002)；试验组二氧化碳降低与对照组比较差异无统计学意义(P=0.988)。
6治疗后试验组CD4~+、CD4~+/CD8+轻度上升,CD8+与治疗前比较明显回升(P＜0.01)。对照组CD4~+,CD8+台疗后较治疗前轻度升高,CD4~+/CD8+下降,无统计学差异(P＞0.05)。各指标试验组与对照组差异无统计学意义(P>0.05)。
7两组治疗后MMRC评分均较治疗前下降,试验组呼吸困难评分下降与对照组差异有统计学意义(P=0.007)。
8 AECOPD呼吸衰竭患者外周血单核细胞CD14~+低于正常人组,与稳定期患者比较显著下降(P<0.05)；AECOPD呼吸衰竭患者CD14蛋白(荧光强度)表达低于稳定期组和正常人组,差异无统计学意义(P>0.05)；AECOPD呼吸衰竭患者TLR4阳性细胞相对百分率高于稳定期组和正常人组,两组与正常人组间差异有统计学意义(P<0.05)；AECOPD呼吸衰竭患者TLR4平均荧光强度高于稳定期组和正常人组,各组间差异无统计学意义(P>0.05)。
9治疗后试验组CD14阳性细胞数与治疗前比较轻度上升(P>0.05),CD14蛋白(荧光强度)轻度下降(P＞0.05),与对照组比较差异无统计学意义(P>0.05)；治疗后试验组TLR4阳性细胞数和TLR4蛋白(荧光强度)轻度下降(P>0.05),与对照组比较差异无统计学意义(P>0.05)。
10治疗后试验组血单核细胞TLR4mRNA.CD14mRNA. NF-κBp65mRNA水平均较对照组下降趋势显著,其中CD14mRNA与对照组比较有显著差异(P=0.020)。
11治疗后试验组血清CRP下降明显,与对照组有显著差异(P=0.045)。
12治疗后试验组血清β-EP, IL-1b、IL-6、IL-8、TNF-α水平均出现下降,对照组大都变化不明显或持续上升,试验组与对照组在IL-8(P>=0.047)、TNF-α(P=0.032)比较有显著性差异。试验组IFN-γ轻度上升,对照组第7天上升,第14天下降到治疗前水平，两组比较无显著差异(P>0.05)。
13安全性评价方面,辨证治疗AECOPD安全有效,未出现严重不良反应,最常见的不良事件是腹泻,腹胀。两组间无显著差异(P>0.05)。
结论
1辨证治疗AECOPD呼吸衰竭临床效果显著。能够降低咳嗽、咯痰、喘息、气短、乏力、心悸、烦燥、腹胀等症状积分,降低浮肿的体征积分；提高动脉血氧分压(PaO2)；降低呼吸困难评分(MMRC);降低APACHEⅡ评分。
2外周血单核细胞免疫功能与AECOPD呼吸衰竭的发病有关。
3中医辨证治疗AECOPD呼吸衰竭的机制可能与下调单核细胞表面TLR4的表达,减轻TLR4和NF-kB介导的炎症反应有关。CRP、IL-8、TNF-α水平与病情严重程度有关,可能可作为判断AECOPD病情严重程度的候选指标。
4辨证治疗在减少VAP发生率方面有一定优势；在插管率、拔管率方面显示了较好的趋势,但无统计学意义,可能与样本量较少有关；在降低病死率方面与对照组比较无显著差异。
Objective
chronic obstructive pulmonary disease (COPD) combined with acute respiratory failure are key drivers of morbidity and mortality, which results in an economic and social burden that is both substantial and increasing. It is reported that treatment with Traditional Chinese Medicine(TCM) may do some benefit to the disease, but the quality of evidence is poor, and mechanism about TCM treatment is not so clear. Inflamation induced by inflammatory cells appears to be amplified in patients who develop COPD. TLRs (Toll-like receptors) comprise a family of proteins whose function is principally to facilitate the detection of, and response to pathogens, viruses, bacteria and fungi can all activate TLR signaling pathway, and these signals have important roles in the activation of COPD host defence. But most of our knowledge of TLRs has emerged from studies of animals. The contribution of TLRs function to human COPD is less advanced.
To investigate clinical therapeutic effect of patients with AECOPD and respiratory failure by treatment of syndromes differentiation of TCM, and the pathogenesis of treatment of syndromes differentiation of TCM, their cellular and molecular mechanisms, and how these underlie physiologic abnormalities and symptoms characteristic of the disease.
Methods
Of a total of 104 patients, we randomly assigned 52 to the control group and 52 to the experimental group. The control group were treated by conventional medicine treatment, the experimental group were treated by TCM besides conventional medicine treatment. The primary efficacy endpoint was mortality, intubation and extubation rate and VAP rate. Secondary endpoints included health status measured by symptomes scores, APACHEⅡscores, blood rutine examination, blood gas analysis and MMRC scores (measured the 0,4,7,14 day after study medication). The expression of TLR4 surface molecules on human CD 14~+ monocytes was assessed using FACS analysis by flow cytometry (measured the 0 and 14 day), so is CD4~+、CD8+T cells. The TLR4mRNA、CD14mRNA、NF-κBp65 mRNA of human CD 14~+ monocytes was assessed by Reverse Transcriptase Polymerase Chain Reaction method(measured the 0,7,14 day)..β-EP、IL-1b、IL-6、IL-8、TNF-α、IFN-γin peripheral blood of patients were assessed by means of enzyme linked immunosorbent assay method(measured the 0,7,14 day). Safety was assessed by documenting all adverse events. Routine examination of blood, urine, stools, liver and renal function, electrocardiograms were performed at days 0 and 14.
Results
Of a total of 104 patients,52 were assigned to the control group and 52 to the experimental group.3 in experimental group and 4 in the control group drop out.
1 2(3.85%) of patients in experimental group died compared with 3 (5.77%) in the control group (P=0.6467).8 (15.38%) of patients in experimental group intubated compared with 11 (21.15%) in the control group(P=0.6118).6(75.0%) extubated in experimental group compared with 4(36.36%) in the control group(P=0.0959). More ventilator-associated pneumonia were reported in the control group relative to experimental group (P=0.0397).
2 The clinical status in experimental groups decreased significantly compared to the control group during the study period(P=0.041), and so was the symptomes scores(P=0.016). There was no significant difference about scores of signs between the two groups (P=0.322).Score of the independent item such as cough, expectoration, gasping, short breath, lack of power, palpitation, upset, abdominal distension and edema decreased significantly compared to the control group during the study period. Dyspnea, sweating, headache, paraphasia, anorexia, wheezing, cyanosis and mental status scores of TCM patients showed no difference to the control group.
3 APACHEⅡscore were decreased in both the two groups at days 14, it was lower in the experimental treatment group than the control group during the study period (P=0.040)
4 Total white cell count in peripheral blood and the neutrophil percentage decreased in the two groups at days 14, it was lower in the experimental treatment group during the study period, there was no major difference between the two groups(P=0.336, P=0.517).
5 Arterial oxygen tension(PaO_2) increased in both the two groups during the study period, it was higher in the experimental treatment group, and there was significant difference between the two groups(P=0.002). Partial pressure of carbon dioxide (PaCO2) in the experimental treatment group showed no significant difference to the conventional treated patients (P=0.988).
6 CD4(+) T cells and ratio of CD4~+/CD8~+ increased in AECOPD patients, CD8(+) T cells in experimental group increased over the study period(P<0.01), CD4(+), CD8(+) T cells in control group increased too ratio of CD4~+/CD8+ decreaced. there were no significant difference between the two groups(P>0.05).
7 The MMRC dyspnoea scale scores decreased in both group during the study period (P=0.000), it was lower in the experimental treatment group than the control group during the study period (P=0.007)
8 CD 14 on AECOPD patients peripheral blood monouclear cell were little lower compared to normal using FACS analysis, and decreased significantly compared to the stable COPD patients (P<0.05). the CD 14 X-mean expressed elevated in stable COPD patients and decreased in severe AECOPD patients, there were no significant difference between them. TLR4 was elevated in stable and AECOPD patients as compared to normal ones, there was significant difference between COPD patients and normals (P<0.05). TLR4 X-mean expressed elevated in stable and AECOPD patients, there was no significant difference between three groups.
9 CD 14 expression were elevated in the experimental(P>0.05) and down-regulated in control group(P>0.05) after treatment. CD14 X-mean expression were not changed much in both groups, and there was no significant difference between them. Expression of TLR4 on monouclear cell were similar in the two groups, and reduced over the treatment period, there was no significant difference as compared to before treatment. TLR4 X-mean expression down-regulated in experimental group and control group, there was no significant difference as compared to before treatment and between them(P>0.05).
10 Compared with the control group, TLR4mRNA、CD14mRNA. NF-κBp65mRNA in monocyte of the experimental group decreased after treatment, The expression levels of CD14mRNA decreased significantly(P=0.020)
11 C-reactive protein in serum was reduced in both the two groups after treatment, CRP in the experimental group reduced more compare to the control group (P=0.045).
12 The level ofβ-EP、IL-1b、IL-6、IL-8、TNF-αin serum was reduced in the experimental group after treatment, all the cytokines in the experimental group reduced more than the control group, especially the IL-8 (P=0.047) and TNF-α(P=0.032). IFN-γin serum was increased gently in the experimental group, but no more than the control group (P<0.05).
13 Safety evaluation, treatment by syndromes differentiation of TCM is safe and effective, no severe adverse reaction reported. Only a few reporting some adverse event, the most frequent of which were diarrhea and abdominal distension.
Conclusion
1 Treatment by syndromes differentiation of TCM to patients with COPD exacerbations and respiratory failure have obvious therapeutic effect. It can relieve clinical symptoms, decrease APACHEⅡscore and the MMRC dyspnea scale outcome. The mechanism of action may related to the following reason.
2 CD 14 and TLR4 expression on monouclear cell increaced in patients with AECOPD and respiratory failure, so peripheral blood monouclear cell may related to the disease.
3 TCM may have the role cf inhibiting activation of TLR4 and nuclear factor-kappaB signaling pathway on peripheral blood monoeytes in patients with AECOPD with respiratory failure, which may associated with reduced cytokine concentration, then relieving the sytemic inflammatory responses. The concentration of CRP、IL-8、TNF-αrelevant to severity of the disease, and maybe it can be take as a biomarker for AECOPD.
4 The experimental group have some advantage in VAP rate. The experimental group have less in intubation and more extubation patients, given more sample, it might be a difference conclusion. There were no significant difference in death rate in the two groups,
引文
[1]庞辉群,熊旭东.呼吸衰竭的中医病因病机认识.中国中医急症.2005,14(4)：336-337.
[2]韩云,林燕钊,张忠德,等.晁恩样教授治疗COPD呼吸衰竭经验介绍.新中医.2007,39(4)：8-9.
[3]方统念,赵静.浅谈扶阳法在呼吸衰竭治疗中的应用.中国中医急症.2007,16(8)：954,958.
[4]洪广祥.中医药论治呼吸衰竭.中医药通报,2007,6(4)：6-11.
[5]武维屏,冯淬灵.谈慢性呼吸衰竭三期十候辨治.安徽中医学院学报.2001,20(1)：3-4.
[6]霍博雅,王庆.慢性呼吸衰竭的中医分型与血气分析之间的关系.中医药学刊.2002,20(6)：751,760.
[7]杨惠琴,楚东岭.肺心病II型呼吸衰竭伴营养不良与中医分型相关性分析.第四军医大学学报2009,30(10)：919.
[8]李学明.辨证论治配合西药治疗慢性呼吸衰竭34例.陕西中医.2006,27(12)：1462-1463.
[9]徐艳文.辨证论治结合西医治疗COPD合并呼吸衰竭40例.浙江中西医结合杂志.2008,18(9)：551-552.
[10]韩云,林嬿钊,李芳.有创序贯无创机械通气配合中医药治疗慢性阻塞性肺疾病急性呼吸衰竭临床观察.辽宁中医杂志.2006,33(5)：555-557.
[11]黄斌,王筠,张静.中西医结合治疗呼吸衰竭的临床探讨.中国中医急症.2007,16(1)：55-57.
[12]马振峰.中西医结合并分型治疗肺心病呼吸衰竭.实用中医内科杂志.2008,22(3)：44.
[13]钟世杰、谭荣益、刘涛等.中西医结合治疗中、重度呼吸衰竭临床研究.中国中医急症.2003,12(1)：1-2.
[14]何德平,韩云,陈伯钧.中西医结合治疗慢性阻塞性肺疾病致严重呼吸衰竭10例.新中医.2002,34(7)：40-41.
[15]惠萍,吴海云,伍方红.中西医结合治疗慢性阻塞性肺疾病慢性加重合并呼吸衰竭的临床研究.新中医.2005,37(5)：62-63.
[16]李清华.中西医结合治疗慢性阻塞性肺疾病并呼吸衰竭85例疗效观察.河北中医.2008,30(7)：734-735.
[17]何德平,林琳,吴蕾.中医药对慢阻肺呼吸衰竭机械通气患者作用的临床研究.新中医.2006,38(11)：42-43.
[18]陈燕,王辛秋,杨道文.豁痰祛瘀汤治疗肺心病合并呼吸功能衰竭53例.中国中医药信息杂志.2002,年9(9)：43-44.
[19]傅大海,邵燕燕.化瘀祛痰泻肺法配合抗生素治疗慢性呼吸衰竭50例.陕西中医.2003,24(10)：867-868.
[20]周继朴.慢性阻塞性肺病合并呼吸衰竭患者长期氧疗配合中药汤剂治疗的研究.中华中医药学刊,2009,27(10)：2238-2240.
[21]周喜忠,顾江萍,孙桐杰.通活汤治疗呼吸衰竭48例.中医药信息.2000,17(2)：22.
[22]蒋志诚.中西医结合治疗慢性肺心病呼吸衰竭38例总结.湖南中医杂志.2006,22(3)：11-12.
[23]王军.中西医结合治疗肺心病慢性呼吸衰竭32例.中国中医急症.2004,13(11)：774.
[24]戴安伟.中西医结合治疗Ⅱ型呼吸衰竭42例.河南中医.2005,25(10)：66.
[25]杨周瑞.中西医结合治疗慢性呼吸衰竭临床研究.中国中医急症.2004,10(2)：69-70.
[26]陈沁,洪旭初,蔡勇,等.中西医结合治疗慢性阻塞性肺疾病合并急性呼吸衰竭30例.2005,36(5)：3-5.
[27]翁燕娜,韩云,李芳等.健脾益肺冲剂治疗慢性阻塞性肺疾病呼吸衰竭疗效观察.陕西中医.2009,30(12)：1578-1579.
[28]庞辉群,熊旭东,严慧萍等.肺肃清煎剂对COPD急性发作并呼吸衰竭患者血气分析及血液流变学的影响.上海甲医药大学学报,2006,20(4)：54-56.
[29]庞辉群,熊旭东,李凤森,等.泻热化痰祛瘀法治疗慢性阻塞性肺疾病急性发作并呼吸衰竭疗效观察.中国中医急症2007,16(2)：135-137.
[30]张瑜,李剑莹,邓屹琪,等.清肺化痰中药配合呼吸机无创正压通气救治慢性阻塞性肺病伴呼吸衰竭的疗效观察.广州中医药大学学报.2007,24(3)：205-207.
[31]李素云,马利军,吴其标.益气活血化痰开窍法为主治疗慢性阻塞性肺疾病合并呼吸衰竭疗效观察.中国中医急症.2002,11(1)：9-10.
[32]范发才,李影捷,惠萍,等.益气化痰法联合无创通气治疗慢性阻塞性肺疾病并呼吸衰竭临床观察.中华中医药学刊.2009,27(8)：1787-1789.
[33]杨道文,张洪春.泻浊纳气汤对慢性Ⅱ型呼吸衰竭患者2,3-二磷酸甘油酸的影响.北京中医药大学学报.2000,23(5)：60-62.
[34]罗义,张艳萍,刘冰.无创正压通气联合中药治疗COPD Ⅱ型呼吸衰竭75例临床观察.辽宁中医杂志.2007,34(4)：476-477.
[35]钟勇.中西医结合治疗呼吸衰竭的临床分析.中国现代药物应用.2009,3(22)：92-93.
[36]刘志文,焦河玲.中西医结合治疗呼吸衰竭72例.中医研究.2006,19(10)：30-31.
[37]黄青松.中西医结合治疗肺心病合并呼吸功能衰竭疗效观察.中国中医急症.2007,16(8)：904,953.
[38]刘武年,闫丽.中西医结合治疗慢性阻塞性肺疾病呼吸衰竭60例临床观察.河北中医.2008,30(3)：280.
[39]谈欧,史锁芳,王德钧.中西医结合治疗慢性阻塞性肺病所致呼吸衰竭临床观察.中国中医药信息杂志.2006,13(8)：61-62.
[40]徐艳玲,刘德华.参麦注射液治疗慢性阻塞性肺疾病并呼吸衰竭临床研究.辽宁中医杂志.2005,32(10)：1042-1043.
[41]周敏杰,封启明.参附注射液治疗慢性阻塞性肺疾病合并呼吸衰竭疗效观察.中国中医急症.2006,16(12)：1481-1482.
[42]李逢春,范滨,郝伟,等.清开灵合复方丹参注射液治疗肺心病呼吸衰竭临床观察.中国中医急症.2003,12(5)：435-436.
[43]乔亚红,刘俊刚,汤兵祥.痰热清注射液治疗COPD并呼吸衰竭26例.中医研究.2005,18(6)：43-44.
[44]钟兴美,周波,张宇.痰热清注射液联合机械通气治疗COPD并发呼吸衰竭24例.中国中医急症.2009,18(2)：283-284.
[45]鲍滨.痰热清联合抗生素治疗呼吸衰竭疗效观察.中国中医急症.2008,17(10)：1351-1352,1376.
[46]张清伟,杨清华,吴海珊,等.痰热清治疗呼吸衰竭气管插管/切开术后痰潴留疗效分析.中国中医急症.2007,16(2)：153,155.
[47]李振仁,谷元奎,艾庆岩.细辛脑注射液合川芎嗪注射液治疗肺心病呼吸衰竭疗效观察.中医药 临床杂志,2004,16(3)：257-258.
[48]张庆年,李萍.川芎嗪治疗慢性阻塞性肺疾病急性加重期合并呼吸衰竭疗效观察.中国中医急症.2007,17(8)：1051,1067.
[49]顾伟民,杨大赋.丹红注射液配合无创机械通气治疗慢性阻塞性肺病伴2型呼吸衰竭的临床观察.中华中医药学刊.2008,26(10)：2298-2300.
[50]王立军,张雅莉,李倜.消喘胶囊治疗慢性呼吸衰竭30例临床观察.中国中医药科技.2003,10(6)：380-381.
[51]刘勤建.通心络胶囊治疗喘息型支气管炎急性加重期伴呼吸衰竭40例.中国中医药现代远程教育.2009,7(5)：27.
[52]李伟,孙建,唐艳芬等.中药雾化结合BiPAP治疗COPD伴II型呼吸衰竭42例临床观察.甘肃中医.2007,20(2)：20-22.
[53]韦宏庆,刁人政.中药呼衰雾化剂治疗慢性呼吸衰竭加重期30例临床研究.安徽中医临床杂志.2002,12(1)：21-22.
[54]张伟,孙志佳,刘建博,等.中药灌洗联合机械通气序贯治疗COPD并发呼吸衰竭23例疗效观察.新中医.2006,38(2)：56-57.
[55]刘建博,刘小虹.清开灵注射液支气管肺泡灌洗治疗肺心病呼吸衰竭60例.中国中医急症.2001,10(4)：208-209.
[56]韩云,林嬿钊.中药灌肠联合无创通气治疗COPD急性加重期呼吸衰竭.福建中医学院学报.2006,16(2)：9-12.
[57]林嬿钊,韩云,李芳.通下法配合无创通气治疗慢性阻塞性肺疾病急性加重期呼吸衰竭15例.新中医.2005,37(1)：41-43.
[58]罗友根.丹参对油酸引起的急性肺损伤治疗作用的实验研究[J].河南职工医学院学报,2005,17(6)：328-329.
[59]陆健,张小虎,区永欣,古继红,田丙坤,.祛痰逐水法对实验性大鼠急性肺损伤的影响.中华中医药学刊,2008,26(06)：1347-1349.
[60]曹春水,黄亮.复方丹参对早期急性肺损伤炎性介质的影响[J].江西医药,2007,42(3)：208-211.
[61]刘红菊,陶晓南,辛建宝,等.中药热毒宁对急性肺损伤兔肺内致炎因子的影响.中国新药与临床杂志.2007,26(6)：446449.
[62]黄翠萍,杨和平,张珍祥.参麦注射液对脂多糖诱导大鼠急性肺损伤防护机制探讨[J].中华结核和呼吸杂志,2005,28(1)：67-68.
[63]赵晓琴,张剑锋,邝晓聪等.甘草酸二铵对急性肺损伤大鼠肺泡巨噬细胞白细胞介素10及18表达的影响[J].中华结核和呼吸杂志,2004,27(2)：126-127.
[64]李臣鸿,刘晓晴,张珍祥等.急性肺损伤时黄芪对核因子K13及白细胞介素6mRNA表达的影响[J].中华结核和呼吸杂志,2002,25(3)：189-190.
[65]田玉芝,陈瑞丰,杨俊山,等.胰炎合剂治疗大鼠急性坏死性胰腺炎肺损伤NF-KB活性的研究.中国中西医结合外科杂志.2007,13(2)：167-171.
[66]李建生,张卫红,赵君玫等.川芎嗪和参麦注射液对脑缺再灌注肺损伤老龄大鼠ATP酶和自由基代谢的影响[J].中国中西医结合急救杂志,2001,8(4)：210-211.
[67]曹慧玲,吕士杰,姜艳霞,等.急性肺损伤大鼠氧自由基变化及不同中药治疗作用的对比.中国中西医结合急救杂志.2006,13(3)：146-149.
[68]苏建玲,李星海,佟飞,等.银杏叶提取物对急性百草枯中毒大鼠肺过氧化损伤的保护作用[J].中华劳动卫生职业病杂志,2003,21(3)：226-227.
[69]耿耘.加减陷胸桃承汤合参麦针防治油酸型ARDS动物的实验观察[J].中国医药学报,2000,15(3)：34-36.
[70]阮秋蓉,宋建新,邓仲端等.山莨菪碱对血管内皮细胞组织因子和纤溶酶原激活物抑制剂1表达的影响及其机制研究[J].中国中西医结合杂志,2004,24(5)：422.
[71]王海峰,李建生,李素云,等.中医药治疗慢性呼吸衰竭研究进展.中国中医基础医学杂志,2010,16(12)：1191-1193.
[1]Global Initiative For Chronic Obstructive.Global strategy for diagnosis, management, and prevention of COPD [Internet] [updated 2009]. http://www.goldcopd.org.
[2]TSOUMAKIDOU M, TZANAKIS N, KYRIAKOU D, et al. Inflammatory cell profiles and T-lymphocyte subsets in chronic obstructive pulmonary disease and severe persistent asthma[J]. Clin Exp Allergy,2004,34(2):234-240.
[3]BARNES P J. Mediators of chronic obstructive pulmonary disease[J]. Pharmacol Rev,2004,56(4):515-548.
[4]QUINT J K, WEDZICHA J A. The neutrophil in chronic obstructive pulmonary disease[J]. J Allergy Clin Immunol, 2007,119(5):1065-1071.
[5]PROFITA M, SALA A, BONANNO A, et al. Chronic obstructive pulmonary disease and neutrophil infiltration:role of cigarette smoke and cyclooxygenase products[J]. Am J Physiol Lung Cell Mol Physiol,2010,298(2):L261-L269.
[6]SHAPIRO S D. The macrophage in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,1999,160(5 Pt 2):S29-S32.
[7]PONS J, SAULEDA J, FERRER J M, et al. Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease[J]. Eur Respir J,2005,25(3):441-446.
[8]TSAI J J, LIAO E C, HSU J Y, et al. The differences of eosinophil-and neutrophil-related inflammation in elderly allergic and non-allergic chronic obstructive pulmonary disease[J]. J Asthma,2010,47(9):1040-1044.
[9]VERMAELEN K, PAUWELS R. Pulmonary dendritic cells[J]. Am J Respir Crit Care Med,2005,172(5):530-551.
[10]BANCHEREAU J, STEINMAN R M. Dendritic cells and the control of immunityfJ]. Nature,1998,392(6673):245-252.
[11]COSIO M G, SAETTA M, AGUSTI A. Immunologic aspects of chronic obstructive pulmonary disease[J]. N Engl J Med, 2009,360(23):2445-2454.
[12]FINKELESTEIN R, FRASER R S, GHEZZO H, et al. Alveolar inflammation and its relation to emphysema in smokers[J]. Am J Respir Crit Care Med,1995,152(5 Pt 1):1666-1672.
[13]SAETTA M, DI STEFANO A, MAESTRELLI P, et al. Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis[J]. Am Rev Respir Dis,1993,147(2):301-306.
[14]TSOUMAKIDOU M, DEMEDTS I K, BRUSSELLE G G, et al. Dendritic cells in chronic obstructive pulmonary disease:new players in an old game[J]. Am J Respir Crit Care Med,2008,177(11):1180-1186.
[15]DEMOOR T, BRACKE K. R, VERMAELEN K Y, et al. CCR7 modulates pulmonary and lymph node inflammatory responses in cigarette smoke-exposed mice[J]. J Immunol,2009,183(12):8186-8194.
[16]BRACKE K, CATALDO D, MAES T, et al. Matrix metalloproteinase-12 and cathepsin D expression in pulmonary macrophages and dendritic cells of cigarette smoke-exposed mice[J]. Int Arch Allergy Immunol,2005,138(2):169-179.
[17]TZORTZAKI E G, SIAFAKAS N M. A hypothesis for the initiation of COPD[J]. Eur Respir J,2009,34(2):310-315.
[18]VASSALLO R, WALTERS P R, LAMONT J, et al. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study[J]. Respir Res,2010,11:45.
[19]FREEMAN C M, MARTINEZ FJ, HAN M K, et al. Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2009,180(12):1179-1188.
[20]TSOUMAKIDOU M, KOUTSOPOULOS A V, TZANAKIS N, et al. Decreased small airway and alveolar CD83+ dendritic cells in COPD[J]. Chest,2009,136(3):726-733.
[21]TSOUMAKIDOU M, BOULOUKAKI I, KOUTALA H, et al. Decreased sputum mature dendritic celis in healthy smokers and patients with chronic obstructive pulmonary disease[J]. Int Arch Allergy Immunol,2009,150(4):389-397.
[22]ROGERS A V, ADELROTH E, HATTOTUWA K, et al. Bronchial mucosal dendritic cells in smokers and ex-smokers with COPD:an electron microscopic study[J]. Thorax,2008,63(2):108-114.
[23]BROKAW J J, WHITE G W, BALUK P, et al. Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa[J]. Am J Respir Cell Mol Biol,1998,19(4):598-605.
[24]MARTORANA P A, LUNGHI B, LUCATTELLI M, et al. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice[J]. BMC Pulm Med,2008,8:17.
[25]LAMBRECHT B N, HAMMAD H. Lung dendritic cells:targets for therapy in allergic disease[J]. Handb Exp Pharmacol, 2009(188):99-114.
[26]GADGIL A, DUNCAN S R. Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2008,3(4):531-541.
[27]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2003,168(8):968-975.
[28]WOOLHOUSE I S, BAYLEYD L, STOCKLEY R A. Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8[J]. Thorax, 2002,57(8):709-714.
[29]CROOKS S W, BAYLEY D L, HILL S L, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis:the role of leukotriene B4[J]. Eur Respir J,2000,15(2):274-280.
[30]Ko F W, LEUNG T F, WONG G W, et al. Measurement of tumor necrosis factor-alpha, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2009,4:79-86.
[31]PINTO-PLATA V M, LIVNAT G, GIRISH M, et al. Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD[J]. Chest,2007,131(1):37-43.
[32]BEEH K M, KORNMANN O, BUHL R, et al. Neutrophil chemotactic activity of sputum from patients with COPD:role of interleukin 8 and leukotriene B4[J]. Chest,2003,123(4):1240-1247.
[33]ZHANG Y, YANG S R, CHENG D Y. [The effect of glucocorticoid on IL-8 expressing in lung tissue of rat with chronic obstructive pulmonary disease][J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2007,38(2):287-290.
[34]MILLER A L, STRIETER R M, GRUBER A D, et al. CXCR2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction[J]. J Immunol,2003,170(6):3348-3356.
[35]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2001,163(2):349-355.
[36]SULKOWSKA M, SULKOWSKI S, TERLIKOWSKI S, et al. Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type Ⅱ alveolar epithelial cells[J]. Pol J Pathol,1997,48(3):179-188.
[37]KEATINGS V M, COLLINS P D, SCOTT D M, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma[J]. Am J Respir Crit Care Med, 1996,153(2):530-534.
[38]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2001,163(2):349-355.
[39]CHURG A, WANG R D, TAI H, et al. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse[J]. Am J Respir Crit Care Med,2004,170(5):492-498.
[40]KARADAG F, KARUL A B, CILDAG O, et al. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD[J]. Lung,2008,186(6):403-409.
[41]WOOD AM, SIMMONDSM J, BAYLEY D L, et al. The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency[J]. Respir Res,2008,9:52.
[42]SAPEY E, WOOD A M, AHMAD A, et al. Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2010,182(2):192-199.
[43]RENNARD S I, FOGARTY C, KELSEN S, et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(9):926-934.
[44]DENTENER M A, CREUTZBERG E C, PENNINGS H J, et al. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease:a pilot study[J], Respiration,2008,76(3):275-282.
[45]SUISSA S, ERNST P, HUDSON M. TNF-alpha antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2008,21 (1):234-238.
[46]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[47]CULPITT S V, ROGERS D F, SHAH P, et al. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,167(1):24-31.
[48]RUSZNAK C, MILLS P R, DEVALIA J L, et al. Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol,2000,23(4):530-536.
[49]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[50]SINGH B, ARORA S, KHANNA V. Association of severity of COPD with IgE and interieukin-1 beta[J]. Monaldi Arch Chest Dis,2010,73(2):86-87.
[51]MAHAJAN B, VIJAYAN V K, AGARWAL M K, et al. Serum interleukin-1 beta as a marker for differentiation of asthma and chronic obstructive pulmonary disease[J]. Biomarkers,2008,13(7):713-727.
[52]DROEMANN D, GOLDMANN T, TIEDJE T, et al. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients[J]. Respir Res,2005,6:68.
[53]PONS J, SAULEDA J, REGUEIRO V, et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease[J]. Respir Res,2006,7:64.
[54]POLTORAK A, HE X, SMIRNOVA I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:mutations in Tlr4 gene[J]. Science,1998,282(5396):2085-2088.
[55]ZHANG X, SHAN P, JIANG G, et al. Toll-like receptor 4 deficiency causes pulmonary emphysema[J]. J Clin Invest, 2006,116(11):3050-3059.
[1]Global Initiative For Chronic Obstructive.Global strategy for diagnosis, management, and prevention of COPD [Internet] [updated 2009]. http://www.goldcopd.org.
[2]National Heart, Lung, and Blood Institute.2004 NHLBI morbidity and mortality chartbook on cardiovascular, lung and blood diseases [Internet]. Bethesda, MD:U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health [accessed 2007 Jul 26].[EB/OL]. http://www.nhlbi.nih.gov/resources/docs/cht-book.htm.
[3]LOPEZ A D, MURRAY C C. The global burden of disease,1990-2020[J]. Nat Med,1998,4(11):1241-1243.
[4]LOPEZ A D, SHIBUYA K, RAO C, et al. Chronic obstructive pulmonary disease:current burden and future projections[J]. Eur Respir J,2006,27(2):397-412.
[5]SEEMUNGAL T A, DONALDSON G C, BHOWMIK A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2000,161(5):1608-1613.
[6]KANNER R E, ANTHONISEN N R, CONNETT J E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease:results from the lung health study[J]. Am J Respir Crit Care Med,2001,164(3):358-364.
[7]MACNEE W. Acute exacerbations of COPD[J]. Swiss Med Wkly,2003,133(17-18):247-257.
[8]MCCRORY D C, BROWN C, GELFAND S E, et al. Management of acute exacerbations of COPD:a summary and appraisal of published evidence[J]. Chest,2001,119(4):1190-1209.
[9]CONNORS A J, DAWSON N V, THOMAS C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments)[J]. Am J Respir Crit Care Med,1996,154(4 Pt 1):959-967.
[10]GROENEWEGEN K H, SCHOLS A M, WOUTERS E F. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD[J]. Chest,2003,124(2):459-467.
[11]NEVINS M L, EPSTEIN S K. Predictors of outcome for patients with COPD requiring invasive mechanical ventilation[J]. Chest,2001,119(6):1840-1849.
[12]KANNER R E, ANTHONISEN N R, CONNETT J E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease:results from the lung health study[J]. Am J Respir Crit Care Med,2001,164(3):358-364.
[13]SCHUMAKER G L, EPSTEIN S K. Managing acute respiratory failure during exacerbation of chronic obstructive pulmonary disease[J]. Respir Care,2004,49(7):766-782.
[14]QUON B S, GAN W Q, SIN D D. Contemporary management of acute exacerbations of COPD:a systematic review and metaanalysis[J]. Chest,2008,133(3):756-766.
[15]KUNISAKI K. M, RICE K L, NIEWOEHNER D E. Management of acute exacerbations of chronic obstructive pulmonary disease in the elderly:an appraisal of published evidence[J]. Drugs Aging,2007,24(4):303-324.
[16]有创-无创序贯机械通气多中心研究协作组.以肺部感染控制窗为切换点行有创与无创序贯机械通气治疗慢性阻塞性肺疾病所致严重呼吸衰竭的随机对照研究[J].中华结核和呼吸杂志,2006(1)：14-18.
[17]SENEFF M G, WAGNER D P, WAGNER R P, et al. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease[J]. JAMA, 1995,274(23):1852-1857.
[18]石占利,方堃,李国辉,等.通腑法对慢性阻塞性肺疾病呼吸衰竭患者呼吸力学及气道炎症因子的影响[J].中华中医药杂志,2010(10).1710-1713.
[19]石占利,方堃,李国辉,等.通腑法对慢性阻塞性肺疾病呼吸衰竭患者胃肠激素水平的干预作用[J].中华中医药学刊,2010(4).815-817.
[20]兰万成,曾靖,罗翌.中西医结合治疗慢性阻塞性肺疾病急性发作期呼吸衰竭的临床观察[J].辽宁中医杂志,2010(2).310-312.
[21]韩云,张燕,谢东平,等.中医调肠法配合无创通气治疗AECOPD呼吸衰竭的临床研究[J].中国中西医结合杂志,2010(8).814-818.
[22]李秀彦.通腑降浊法治疗慢性阻塞性肺疾病呼吸衰竭的疗效观察[J].河北中医,2006(7)：503-504.
[23]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,168(8):968-975.
[24]FUJIMOTO K, YASUO M, URUSHIBATA K, et al. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease[J]. Eur Respir J,2005,25(4):640-646.
[25]PAPI A, BELLETTATO C M, BRACCIONI F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations[J]. Am J Respir Crit Care Med,2006,173(10):1114-1121.
[26]GERN J E, FRENCH D A, GRINDLE K A, et al. Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells[J]. Am J Respir Cell Mol Biol,2003,28(6):731-737.
[27]MERCER P F, SHUTE J K, BHOWMIK. A, et al. MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation[J]. Respir Res,2005,6:151.
[28]FIORENZA D, VIGLIO S, LUPI A, et al. Urinary desmosine excretion in acute exacerbations of COPD:a preliminary report[J]. Respir Med,2002,96(2):110-114.
[29]FRANCIOSI L G, PAGE C P, CELI B R, et al. Markers of exacerbation severity in chronic obstructive pulmonary disease[J]. Respir Res,2006,7:74.
[30]ZHU J, MAJUMDAR S, QIU Y, et al. Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells[J]. Am J Respir Crit Care Med,2001,164(12):2220-2228.
[31]BHOWMIK A, SEEMUNGAL T A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations[J]. Thorax,2000,55(2):114-120.
[32]CARPAGNANO G E, RESTA O, FOSCHINO-BARBARO M P, et al. Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease:effect of carbocysteine lysine salt monohydrate (SCMC-Lys)[J]. Eur J Pharmacol,2004,505(1-3):169-175.
[33]CHAUDHURI N, DOWER S K, WHYTE M K, et al. Toll-like receptors and chronic lung disease[J]. Clin Sci (Lond),2005,109(2):125-133.
[34]GERRITSEN W B, ASIN J, ZANEN P, et al. Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients[J]. Respir Med,2005,99(1):84-90.
[35]BIERNACKI W A, KHARITONOV S A, BARNES P J. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD[J]. Thorax,2003,58(4):294-298.
[36]BHOWMIK A, SEEMUNGAL T A, DONALDSON G C, et al. Effects of exacerbations and seasonality on exhaled nitric oxide in COPD[J]. Eur Respir J,2005,26(6):1009-1015.
[37]HURST J R, DONALDSON G C, PERERA W R, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2006,174(8):867-874.
[38]ANTONESCU-TURCU A L, TOMIC R. C-reactive protein and copeptin:prognostic predictors in chronic obstructive pulmonary disease exacerbations[J]. Curr Opin Pulm Med,2009,15(2):120-125.
[39]RAMMAERT B, VERDIER N, CAVESTRI B, et al. Procalcitonin as a prognostic factor in severe acute exacerbation of chronic obstructive pulmonary disease[J]. Respirology,2009,14(7):969-974.
[40]GERRITSEN W B, ASIN J, ZANEN P, et al. Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients[J]. Respir Med,2005,99(1):84-90.
[41]CREUTZBERG E C, WOUTERS E F, VANDERHOVEN-AUGUSTIN I M, et al. Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2000,162(4 Pt 1):1239-1245.
[42]DROST E M, SKWARSKI K M, SAULEDA J, et al. Oxidative stress and airway inflammation in severe exacerbations of COPD[J]. Thorax,2005,60(4):293-300.
[43]MAEDER M T, BRUTSCHE M H, CHRIST A, et al. Natriuretic peptides for the prediction of severely impaired peak VO2 in patients with lung disease[J]. Respir Med,2009,103(9):1337-1345.
[44]张九进,陈显源,邓海波,等.慢性阻塞性肺疾病患者血浆p-内啡肽水平与呼吸功能的相关性研究[J].实用医学杂志,2003,19(1).39-40.
[45]BARNES P J, CHOWDHURY B, KHARITONOV S A, et al. Pulmonary biomarkers in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2006,174(1):6-14.
[46]李建生.中医药治疗慢性阻塞性肺疾病研究的实践与若干思考[J].河南中医,2065(5)：13-15.
[47]朱文锋.中医内科疾病诊疗常规[M].长沙：湖南科技出版社,1999.
[48]郑筱萸.中药新药临床研究指导原则试行[M].北京：中国医药科技出版社,2002.
[49]王永炎,晃恩祥.今日中医内科中卷[M].北京：人民卫生出版社,2000.
[50]ANTHONISEN N R, MANFREDA J, WARREN C P, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease[J]. Ann Intern Med,1987,106(2):196-204.
[51]CELLI B R, MANNEE W. Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper[J]. Eur Respir J,2004,23(6):932-946.
[52]PAPI A, BELLETTATO C M, BRACCIONI F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations[J]. Am J Respir Crit Care Med,2006,173(10):1114-1121.
[53]SETHI S, EVANS N, GRANT B J, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease[J]. N Engl J Med,2002,347(7):465-471.
[54]WEDZICHA J A. Role of viruses in exacerbations of chronic obstructive pulmonary disease[J]. Proc Am Thorac Soc,2004,1(2):115-120.
[55]WILKINSON T M, DONALDSON G C, JOHNSTON S L, et al. Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2006,173(8):871-876.
[56]MELONI F, PASCHETTO E, MANGIAROTTI P, et al. Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations[J]. J Chemother,2004,16(1):70-76.
[57]LIEBERMAN D, LIEBERMAN D, BEN-YAAKOV M, et al. Infectious etiologies in acute exacerbation of COPD[J]. Diagn Microbiol Infect Dis,2001,40(3):95-102.
[58]MACNEE W, DONALDSON K. Exacerbations of COPD:environmental mechanisms[J]. Chest,2000,117(5 Suppl 2):390S-397S.
[59]RUTTEN F H, CRAMER M J, LAMMERS J W, et al. Heart failure and chronic obstructive pulmonary disease: An ignored combination?[J]. Eur J Heart Fail,2006,8(7):706-711.
[60]ABROUG F, OUANES-BESBES L, NCIRI N, et al. Association of left-heart dysfunction with severe exacerbation of chronic obstructive pulmonary disease:diagnostic performance of cardiac biomarkers[J]. Am J Respir Crit Care Med,2006,174(9):990-996.
[61]BASTIN A J, STARLING L, AHMED R, et al. High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation[J]. Chron Respir Dis, 2010,7(2):91-97.
[62]CONNORS A J, DAWSON N V, THOMAS C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments) [J]. Am J Respir Crit Care Med,1996,154(4 Pt 1):959-967.
[63]TILLIE-LEBLOND I, MARQUETTE C H, PEREZ T, et al. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease:prevalence and risk factors[J]. Ann Intern Med, 2006,144(6):390-396.
[64]DAHL M. Biomarkers for chronic obstructive pulmonary disease:surfactant protein D and C-reactive protein[J]. Am J Respir Crit Care Med,2008,177(11):1177-1178.
[65]DAHL M, VESTBO J, LANGE P, et al. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(3):250-255.
[66]DAHL M, VESTBO J, ZACHO J, et al. C reactive protein and chronic obstructive pulmonary disease:a Mendelian randomisation approach[J]. Thorax,2011,66(3):197-204.
[67]RAMMAERT B, VERDIER N, CAVESTRI B, et al. Procalcitonin as a prognostic factor in severe acute exacerbation of chronic obstructive pulmonary disease[J]. Respirology,2009,14(7):969-974.
[68]SHAKOORI T A, SIN D D, GHAFOOR F, et al. Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease[J]. Dis Markers,2009,27(6):287-294.
[69]李建生.慢性阻塞性肺疾病中医辨证治疗概要[J].河南中医学院学报,2009(4)：9-11.
[70]李建生.关于慢性呼吸衰竭中医诊断及辨证治疗标准的研究[J].中医学报,2010(4)：627-629.
[71]ANTHONISEN N R, WRIGHT E C. Bronchodilator response in chronic obstructive pulmonary disease[J]. Am Rev Respir Dis,1986,133(5):814-819.
[72]CHANGE J H, LEE J H, KIM M K, et al. Determinants of respiratory symptom development in patients with chronic airflow obstruction[J]. Respir Med,2006,100(12):2170-2176.
[73]李建生,王至婉,余学庆,等.中药治疗慢性阻塞性肺疾病稳定期的系统评价[J].辽宁中医杂志,2010,37(2).229-231.
[74]KNAUS W A, DRAPER E A, WAGNER D P, et al. APACHE Ⅱ:a severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[75]KNAUS W A, DRAPER E A, WAGNER D P, et al. APACHE Ⅱ:a severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[76]GOEL A, PINCKNEY R G, LITTENBERG B. APACHE II predicts long-term survival in COPD patients admitted to a general medical ward[J]. J Gen Intern Med,2003,18(10):824-830.
[77]RANIERI P, BIANCHETTI A, MARGIOTTA A, et al. Predictors of 6-month mortality in elderly patients with mild chronic obstructive pulmonary disease discharged from a medical ward after acute nonacidotic exacerbation[J]. J Am Geriatr Soc,2008,56(5):909-913.
[78]RANIERI P, BIANCHETTI A, MARGIOTTA A, et al. Predictors of 6-month mortality in elderly patients with mild chronic obstructive pulmonary disease discharged from a medical ward after acute nonacidotic exacerbation[J]. J Am Geriatr Soc,2008,56(5):909-913.
[79]AYDOGDU M, GURSEL G. Does admission from different sources have any influence on intensive care unit outcome in COPD patients?[J]. Tuberk Toraks,2008,56(4):375-381.
[80]GURSEL G. Determinants of the length of mechanical ventilation in patients with COPD in the intensive care unit[J]. Respiration,2005,72(1):61-67.
[81]连增志,穆传勇,黄建安APACHEⅡ评分与临床肺部感染评分在AECOPD中的应用比较分析[J].临床肺科杂志,2009,14(11).1463-1465.
[82]BARNES P J. New molecular targets for the treatment of neutrophilic diseases[J]. J Allergy Clin Immunol, 2007,119(5):1055-1062,1063-1064.
[83]SINGH D, EDWARDS L, TAL-SINGER R, et al. Sputum neutrophils as a biomarker in COPD:findings from the ECLIPSE study[J]. Respir Res,2010,11:77.
[84]TETLEY T D. Macrophages and the pathogenesis of COPD[J]. Chest,2002,121(5 Suppl):156S-159S.
[85]SHAPIRO S D. Evolving concepts in the pathogenesis of chronic obstructive pulmonary disease[J]. Clin Chest Med,2000,21(4):621-632.
[86]Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party[J]. Lancet, 1981,1(8222):681-686.
[87]Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease:a clinical trial. Nocturnal Oxygen Therapy Trial Group[J]. Ann Intem Med,1980,93(3):391-398.
[88]FLETCHER C M. The clinical diagnosis of pulmonary emphysema; an experimental study[J]. Proc R Soc Med,1952,45(9):577-584.
[89]FLETCHER C M, ELMES P C, FAIRBAIRN A S, et al. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population[J]. Br Med J,1959,2(5147):257-266.
[90]MAHLER D A, WELLS C K. Evaluation of clinical methods for rating dyspnea[J]. Chest, 1988,93(3):580-586.
[91]Dyspnea. Mechanisms, assessment, and management:a consensus statement. American Thoracic Society[J]. Am J Respir Crit Care Med,1999,159(1):321-340.
[92]LIN Y X, Xu W N, LIANG L R, et al. The cross-sectional and longitudinal association of the BODE index with quality of life in patients with chronic obstructive pulmonary disease[J]. Chin Med J (Engl), 2009,122(24):2939-2944.
[93]PALADINI L, HODDER R, CECCHINI I, et al. The MRC dyspnoea scale by telephone interview to monitor health status in elderly COPD patients[J]. Respir Med,2010,104(7):1027-1034.
[94]TSIMOGIANNI A M, PAPIRIS S A, STATHOPOULOS G T, et al. Predictors of outcome after exacerbation of chronic obstructive pulmonary disease[J]. J Gen Intern Med,2009,24(9):1043-1048.
[95]NISHIMURA K, IZUMI T, TSUKINO M, et al. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD[J]. Chest,2002,121(5):1434-1440.
[96]O'SHAUGHNESSY T C, ANSARI T W, BARNES N C, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis:inverse relationship of CD8+ T lymphocytes with FEV1[J]. Am J Respir Crit Care Med, 1997,155(3):852-857.
[97]MUELLER R, CHANEZ P, CAMPBELL A M, et al. Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis[J]. Respir Med,1996,90(2):79-85.
[98]SAETTA M, BARALDO S, TURATO G, et al. Increased proportion of CD8+ T-lymphocytes in the paratracheal lymph nodes of smokers with mild COPD[J]. Sarcoidosis Vase Diffuse Lung Dis,2003,20(1):28-32.
[99]DE JONG.J W, VAN DER BELT-GRITTER B, KOETER G H, et al. Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease:association with smoking, IgE and lung function[J]. Respir Med,1997,91(2):67-76.
[100]CARAMORI G, ROMAGNOLI M, CASOLARI P, et al. Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations[J]. Thorax,2003,58(4):348-351.
[101]DO STEFANO A, CARAMORI G, OATES T, et al. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD[J]. Eur Respir J,2002,20(3):556-563.
[102]CHAPCVAL S P, AL-GARAWI A, LORA J M, et al. Inhibition of NF-kappaB activation reduces the tissue effects of transgenic IL-13[J]. J Immunol,2007,179(10):7030-7041.
[103]SADIKOT R T, ZENG H, JOO M, et al. Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa[J]. J Immunol,2006,176(8):4923-4930.
[104]LORA J M, ZHANGD M, LIAO S M, et al. Tumor necrosis factor-alpha triggers mucus production in airway epithelium through an IkappaB kinase beta-dependent mechanism[J]. J Biol Chem, 2005,280(43):36510-36517.
[105]SATO S, NOMURAF F, KAWAI T, et al. Synergy and cross-tolerance between toll-like receptor (TLR) 2-and TLR4-mediated signaling pathways[J]. J Immunol,2000,165(12):7096-7101.
[106]NOMURA F, AKASHI S, SAKAO Y, et al. Cutting edge:endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression[J]. J Immunol, 2000,164(7):3476-3479.
[107]SABROE I, JONES E C, USHER L R, et al. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes:a critical role for monocytes in leukocyte lipopolysaccharide responses[J]. J Immunol, 2002,168(9):4701-4710.
[108]PRINCE L R, ALLEN L, JONES E C, et al. The role of interleukin-lbeta in direct and toll-like receptor 4-mediated neutrophil activation and survival[J]. Am J Pathol,2004,165(5):1819-1826.
[109]DROEMANN D, GOLDMANN T, TIEDJE T, et al. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients[J]. Respir Res,2005,6:68.
[110]PONS J, SAULEDA J, REGUEIRO V, et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease[J]. Respir Res,2006,7:64.
[111]POLTORAK A, HE X, SMIRNOVA I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene[J]. Science,1998,282(5396):2085-2088.
[112]ZHANG X, SHAN P, JJIANG G, et al. Toll-like receptor 4 deficiency causes pulmonary emphysema[J]. J Clin Invest,2006,116(11):3050-3059.
[113]VOLANAKIS J E. Human C-reactive protein:expression, structure, and function[J]. Mol Immunol, 2001,38(2-3):189-197.
[114]DE TORRES J P, CORDOBA-LANUS E, LOPEZ-AGUILAR C, et al. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients[J]. Eur Respir J,2006,27(5):902-907.
[115]GAN W Q, MAN S F, SIN D D. The interactions between cigarette smoking and reduced lung function on systemic inflammation[J]. Chest,2005,127(2):558-564.
[116]THORLEIFSSON S J, MARGRETARDOTTIR O B, GUDMUNDSSON G, et al. Chronic airflow obstruction and markers of systemic inflammation:results from the BOLD study in Iceland[J]. Respir Med, 2009,103(10):1548-1553.
[117]OMORI H, TSUJI M, SATAt K, et al. Correlation of C-reactive protein with disease severity in CT diagnosed emphysema[J]. Respirology,2009,14(4):551-558.
[118]MAN S F, XING L, CONNETT J E, et al. Circulating fibronectin to C-reactive protein ratio and mortality:a biomarker in COPD?[J]. Eur Respir J,2008,32(6):1451-1457.
[119]KARADAG F, KIRDAR S, KARUL A B, et al. The value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease[J]. Eur J Intern Med,2008,19(2):104-108.
[120]DANIELS J M, SCHOORL M, SNUDERS D, et al. Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD[J]. Chest,2010,138(5):1108-1115.
[121]PERERA W R, HURST J R, WILKINSON T M, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation[J]. Eur Respir J,2007,29(3):527-534.
[122]RUIZ-GONZALEZ A, LACASTA D, IBARZ M, et al. C-reactive protein and other predictors of poor outcome in patients hospitalized with exacerbations of chronic obstructive pulmonary disease[J]. Respirology, 2008,13(7):1028-1033.
[123]TSUNODA K, DOUGE K, AKIYA Y, et al. Beta-endorphin secretion at the time of sudden death due to cardiac or respiratory failure[J]. Nihon Hoigaku Zasshi,1992,46(3):182-188.
[124]NGAIS P, JONES A Y, HUI-CHAN C W, et al. Effect of 4 weeks of Acu-TENS on functional capacity and beta-endorphin level in subjects with chronic obstructive pulmonary disease:a randomized controlled trial[J]. Respir Physiol Neurobiol,2010,173(1):29-36.
[125]MAHLER D A, MURRAY J A, WATERMAN L A, et al. Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD[J]. Eur Respir J,2009,33(4):771-777.
[126]张九进,陈显源,邓海波,等.慢性阻塞性肺疾病患者血浆β-内啡肽水平与呼吸功能的相关性研究[J].实用医学杂志,2003,19(1).39-40.
[127]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[128]CULPiTT S V, ROGERS D F, SHAH P, et al. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2003,167(1):24-31.
[129]RUSZNAK C, MILLS P R, DEVALIA J L, et al. Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol,2000,23(4):530-536.
[130]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[131]SINGH B, ARORAS, KHANNA V. Association of severity of COPD with IgE and interleukin-1 beta[J]. Monaldi Arch Chest Dis,2010,73(2):86-87.
[132]MAHAJAN B, VUAYAN V K, AGARWAL M K, et al. Serum interleukin-1beta as a marker for differentiation of asthma and chronic obstructive pulmonary disease[J]. Biomarkers,2008,13(7):713-727.
[133]ALDONYTE R, JANSSON L, PIITULAINEN E, et al. Circulating monocytes from healthy individuals and COPD patients[J]. Respir Res,2003,4:11.
[134]BOLTON C E, EVANS M, IONESCU A A, et al. Insulin resistance and inflammation-A further systemic complication of COPD[J]. COPD,2007,4(2):121-126.
[135]BARNES P J, CELLI B R. Systemic manifestations and comorbidities of COPD[J]. Eur Respir J, 2009,33(5):1165-1185.
[136]CHAOUAT A, SAVALE L, CHOUAID C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension[J]. Chest,2009,136(3):678-687.
[137]K.UHN C R, HOMER R J, ZHU Z, et al. Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung[J]. Am J Respir Cell Mol Biol,2000,22(3):289-295.
[138]BHOWMIK A, SEEMUNGALT A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations [J]. Thorax,2000,55(2):114-120.
[139]BHOWMIK A, SEEMUNGAL T A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations[J]. Thorax,2000,55(2):114-120.
[140]SONG W, ZHAO J, LI Z. Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD[J]. Chin Med J (Engl),2001,114(11):1140-1142.
[141]BUCCHIONI E, KHARITONOV S A, ALLEGRA L, et al. High levels of interleukin-6 in the exhaled breath condensate of patients with COPD[J]. Respir Med,2003,97(12):1299-1302.
[142]DEBIGARE R, MARQUIS K, COTE C H, et al. Catabolic/anabolic balance and muscle wasting in patients with COPD[J]. Chest,2003,124(1):83-89.
[143]GODOY I, CAMPANA A O, GERALDO R R, et al. Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients[J]. Eur Respir J,2003,22(6):920-925.
[144]HAGEMAN G J, LARIK I, PENNINGS H J, et al. Systemic poly(ADP-ribose) polymerase-1 activation, chronic inflammation, and oxidative stress in COPD patients[J]. Free Radic Biol Med,2003,35(2):140-148.
[145]WEDZICHA J A, SEEMUNGAL T A, MACCALLUM P K, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels[J]. Thromb Haemost,2000,84(2):210-215.
[146]PINTO-PLATA V M, LIVNAT G, GIRISH M, et al. Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD[J]. Chest,2007,131(1):37-43.
[147]WALTER R E, WILK J B, LARSON M G, et al. Systemic inflammation and COPD:the Framingham Heart Study[J]. Chest,2008,133(1):19-25.
[148]SIN D D, MAN S F, MARCINIUK D D, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2008,177(11):1207-1214.
[149]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,168(8):968-975.
[150]WOOLHOUSE I S, BAYLEY D L, STOCKLEY R A. Sputum chemotactic activity in chronic obstructive pulmonary disease:effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8[J]. Thorax,2002,57(8):709-714.
[151]CROOKS S W, BAYLEY D L, HILL S L, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis:the role of leukotriene B4[J]. Eur Respir J,2000,15(2):274-280.
[152]KO F W, LEUNG T F, WONG G W, et al. Measurement of tumor necrosis factor-alpha, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2009,4:79-86.
[153]BEEH K M, KORNMANN O, BUHL R, et al. Neutrophil chemotactic activity of sputum from patients with COPD:role of interleukin 8 and leukotriene B4[J]. Chest,2003,123(4):1240-1247.
[154]ZHANG Y, YANG S R, CHENG D Y. [The effect of glucocorticoid on IL-8 expressing in lung tissue of rat with chronic obstructive pulmonary disease][J]. Sichuan Da Xue Xue Bao Yi Xue Ban, 2007,38(2):287-290.
[155]MILLER A L, STRIETER R M, GRUBER A D, et al. CXCR2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction[J]. J Immunol,2003,170(6):3348-3356.
[156]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2001,163(2):349-355.
[157]SULKOWSKA M, SULKOWSKI S, TERLIKOWSKI S, et al. Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells[J]. Pol J Pathol, 1997,48(3):179-188.
[158]KEATINGS V M, COLLINS P D, SCOTT D M, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma[J]. Am J Respir Crit Care Med,1996,153(2):530-534.
[159]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2001,163(2):349-355.
[160]CHURG A, WANG R D, TAI H, et al. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse[J]. Am J Respir Crit Care Med,2004,170(5):492-498.
[161]KARADAG F, KARUL A B, CILDAG O, et al. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD[J]. Lung,2008,186(6):403-409.
[162]WOOD A M, SIMMONDS M J, BAYLEY D L, et al. The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency [J]. Respir Res,2008,9:52.
[163]SAPEY E, WOOD A M, AHMAD A, et al. Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2010,182(2):192-199.
[164]RENNARD S I, FOGARTY C, KELSEN S, et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(9):926-934.
[165]DENGENER M A, CREUTZBERG E C, PENNINGS H J, et al. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease:a pilot study[J]. Respiration,2008,76(3):275-282.
[166]SUISSA S, ERNST P, HUDSON M. TNF-alpha antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2008.21(1):234-238.
[167]KUMAR R K, WEBB D C, HERBERT C, et al. Interferon-gamma as a possible target in chronic asthma[J]. Inflamm Allergy Drug Targets,2006,5(4):253-256.
[168]COSIO M G, GUERASSIMOV A. Chronic obstructive pulmonary disease. Inflammation of small airways and lung parenchyma[J]. Am J Respir Crit Care Med,1999,160(5 Pt 2):S21-S25.
[169]WANG X Q, PANOUSIS C G, ALFARO M L, et al. Interferon-gamma-mediated downregulation of cholesterol efflux and ABC1 expression is by the Statl pathway[J]. Arterioscler Thromb Vasc Biol,2002,22(5):e5-e9.
[170]ELIAS J A, KANG M J, CROTHERS K, et al. State of the art. Mechanistic heterogeneity in chronic obstructive pulmonary disease:insights from transgenic mice[J]. Proc Am Thorac Soc,2006,3(6):494-498.
[171]TZANAKIS N, CHRYSOFAKIS G, TSOUMAKIDOU M, et al. Induced sputum CD8+ T-lymphocyte subpopulations in chronic obstructive pulmonary disease[J]. Respir Med,2004,98(l):57-65.
[172]SZABO S J, SULLIVAN B M, STEMMANN C, et al. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells[J]. Science,2002,295(5553):338-342.
[173]DI STEFANO A, CARAMORI G, CAPELLI A, et al. STAT4 activation in smokers and patients with chronic obstructive pulmonary disease[J]. Eur Respir J,2004,24(l):78-85.
[2]韩云,林燕钊,张忠德,等.晁恩样教授治疗COPD呼吸衰竭经验介绍.新中医.2007,39(4)：8-9.
[3]方统念,赵静.浅谈扶阳法在呼吸衰竭治疗中的应用.中国中医急症.2007,16(8)：954,958.
[4]洪广祥.中医药论治呼吸衰竭.中医药通报,2007,6(4)：6-11.
[5]武维屏,冯淬灵.谈慢性呼吸衰竭三期十候辨治.安徽中医学院学报.2001,20(1)：3-4.
[6]霍博雅,王庆.慢性呼吸衰竭的中医分型与血气分析之间的关系.中医药学刊.2002,20(6)：751,760.
[7]杨惠琴,楚东岭.肺心病II型呼吸衰竭伴营养不良与中医分型相关性分析.第四军医大学学报2009,30(10)：919.
[8]李学明.辨证论治配合西药治疗慢性呼吸衰竭34例.陕西中医.2006,27(12)：1462-1463.
[9]徐艳文.辨证论治结合西医治疗COPD合并呼吸衰竭40例.浙江中西医结合杂志.2008,18(9)：551-552.
[10]韩云,林嬿钊,李芳.有创序贯无创机械通气配合中医药治疗慢性阻塞性肺疾病急性呼吸衰竭临床观察.辽宁中医杂志.2006,33(5)：555-557.
[11]黄斌,王筠,张静.中西医结合治疗呼吸衰竭的临床探讨.中国中医急症.2007,16(1)：55-57.
[12]马振峰.中西医结合并分型治疗肺心病呼吸衰竭.实用中医内科杂志.2008,22(3)：44.
[13]钟世杰、谭荣益、刘涛等.中西医结合治疗中、重度呼吸衰竭临床研究.中国中医急症.2003,12(1)：1-2.
[14]何德平,韩云,陈伯钧.中西医结合治疗慢性阻塞性肺疾病致严重呼吸衰竭10例.新中医.2002,34(7)：40-41.
[15]惠萍,吴海云,伍方红.中西医结合治疗慢性阻塞性肺疾病慢性加重合并呼吸衰竭的临床研究.新中医.2005,37(5)：62-63.
[16]李清华.中西医结合治疗慢性阻塞性肺疾病并呼吸衰竭85例疗效观察.河北中医.2008,30(7)：734-735.
[17]何德平,林琳,吴蕾.中医药对慢阻肺呼吸衰竭机械通气患者作用的临床研究.新中医.2006,38(11)：42-43.
[18]陈燕,王辛秋,杨道文.豁痰祛瘀汤治疗肺心病合并呼吸功能衰竭53例.中国中医药信息杂志.2002,年9(9)：43-44.
[19]傅大海,邵燕燕.化瘀祛痰泻肺法配合抗生素治疗慢性呼吸衰竭50例.陕西中医.2003,24(10)：867-868.
[20]周继朴.慢性阻塞性肺病合并呼吸衰竭患者长期氧疗配合中药汤剂治疗的研究.中华中医药学刊,2009,27(10)：2238-2240.
[21]周喜忠,顾江萍,孙桐杰.通活汤治疗呼吸衰竭48例.中医药信息.2000,17(2)：22.
[22]蒋志诚.中西医结合治疗慢性肺心病呼吸衰竭38例总结.湖南中医杂志.2006,22(3)：11-12.
[23]王军.中西医结合治疗肺心病慢性呼吸衰竭32例.中国中医急症.2004,13(11)：774.
[24]戴安伟.中西医结合治疗Ⅱ型呼吸衰竭42例.河南中医.2005,25(10)：66.
[25]杨周瑞.中西医结合治疗慢性呼吸衰竭临床研究.中国中医急症.2004,10(2)：69-70.
[26]陈沁,洪旭初,蔡勇,等.中西医结合治疗慢性阻塞性肺疾病合并急性呼吸衰竭30例.2005,36(5)：3-5.
[27]翁燕娜,韩云,李芳等.健脾益肺冲剂治疗慢性阻塞性肺疾病呼吸衰竭疗效观察.陕西中医.2009,30(12)：1578-1579.
[28]庞辉群,熊旭东,严慧萍等.肺肃清煎剂对COPD急性发作并呼吸衰竭患者血气分析及血液流变学的影响.上海甲医药大学学报,2006,20(4)：54-56.
[29]庞辉群,熊旭东,李凤森,等.泻热化痰祛瘀法治疗慢性阻塞性肺疾病急性发作并呼吸衰竭疗效观察.中国中医急症2007,16(2)：135-137.
[30]张瑜,李剑莹,邓屹琪,等.清肺化痰中药配合呼吸机无创正压通气救治慢性阻塞性肺病伴呼吸衰竭的疗效观察.广州中医药大学学报.2007,24(3)：205-207.
[31]李素云,马利军,吴其标.益气活血化痰开窍法为主治疗慢性阻塞性肺疾病合并呼吸衰竭疗效观察.中国中医急症.2002,11(1)：9-10.
[32]范发才,李影捷,惠萍,等.益气化痰法联合无创通气治疗慢性阻塞性肺疾病并呼吸衰竭临床观察.中华中医药学刊.2009,27(8)：1787-1789.
[33]杨道文,张洪春.泻浊纳气汤对慢性Ⅱ型呼吸衰竭患者2,3-二磷酸甘油酸的影响.北京中医药大学学报.2000,23(5)：60-62.
[34]罗义,张艳萍,刘冰.无创正压通气联合中药治疗COPD Ⅱ型呼吸衰竭75例临床观察.辽宁中医杂志.2007,34(4)：476-477.
[35]钟勇.中西医结合治疗呼吸衰竭的临床分析.中国现代药物应用.2009,3(22)：92-93.
[36]刘志文,焦河玲.中西医结合治疗呼吸衰竭72例.中医研究.2006,19(10)：30-31.
[37]黄青松.中西医结合治疗肺心病合并呼吸功能衰竭疗效观察.中国中医急症.2007,16(8)：904,953.
[38]刘武年,闫丽.中西医结合治疗慢性阻塞性肺疾病呼吸衰竭60例临床观察.河北中医.2008,30(3)：280.
[39]谈欧,史锁芳,王德钧.中西医结合治疗慢性阻塞性肺病所致呼吸衰竭临床观察.中国中医药信息杂志.2006,13(8)：61-62.
[40]徐艳玲,刘德华.参麦注射液治疗慢性阻塞性肺疾病并呼吸衰竭临床研究.辽宁中医杂志.2005,32(10)：1042-1043.
[41]周敏杰,封启明.参附注射液治疗慢性阻塞性肺疾病合并呼吸衰竭疗效观察.中国中医急症.2006,16(12)：1481-1482.
[42]李逢春,范滨,郝伟,等.清开灵合复方丹参注射液治疗肺心病呼吸衰竭临床观察.中国中医急症.2003,12(5)：435-436.
[43]乔亚红,刘俊刚,汤兵祥.痰热清注射液治疗COPD并呼吸衰竭26例.中医研究.2005,18(6)：43-44.
[44]钟兴美,周波,张宇.痰热清注射液联合机械通气治疗COPD并发呼吸衰竭24例.中国中医急症.2009,18(2)：283-284.
[45]鲍滨.痰热清联合抗生素治疗呼吸衰竭疗效观察.中国中医急症.2008,17(10)：1351-1352,1376.
[46]张清伟,杨清华,吴海珊,等.痰热清治疗呼吸衰竭气管插管/切开术后痰潴留疗效分析.中国中医急症.2007,16(2)：153,155.
[47]李振仁,谷元奎,艾庆岩.细辛脑注射液合川芎嗪注射液治疗肺心病呼吸衰竭疗效观察.中医药 临床杂志,2004,16(3)：257-258.
[48]张庆年,李萍.川芎嗪治疗慢性阻塞性肺疾病急性加重期合并呼吸衰竭疗效观察.中国中医急症.2007,17(8)：1051,1067.
[49]顾伟民,杨大赋.丹红注射液配合无创机械通气治疗慢性阻塞性肺病伴2型呼吸衰竭的临床观察.中华中医药学刊.2008,26(10)：2298-2300.
[50]王立军,张雅莉,李倜.消喘胶囊治疗慢性呼吸衰竭30例临床观察.中国中医药科技.2003,10(6)：380-381.
[51]刘勤建.通心络胶囊治疗喘息型支气管炎急性加重期伴呼吸衰竭40例.中国中医药现代远程教育.2009,7(5)：27.
[52]李伟,孙建,唐艳芬等.中药雾化结合BiPAP治疗COPD伴II型呼吸衰竭42例临床观察.甘肃中医.2007,20(2)：20-22.
[53]韦宏庆,刁人政.中药呼衰雾化剂治疗慢性呼吸衰竭加重期30例临床研究.安徽中医临床杂志.2002,12(1)：21-22.
[54]张伟,孙志佳,刘建博,等.中药灌洗联合机械通气序贯治疗COPD并发呼吸衰竭23例疗效观察.新中医.2006,38(2)：56-57.
[55]刘建博,刘小虹.清开灵注射液支气管肺泡灌洗治疗肺心病呼吸衰竭60例.中国中医急症.2001,10(4)：208-209.
[56]韩云,林嬿钊.中药灌肠联合无创通气治疗COPD急性加重期呼吸衰竭.福建中医学院学报.2006,16(2)：9-12.
[57]林嬿钊,韩云,李芳.通下法配合无创通气治疗慢性阻塞性肺疾病急性加重期呼吸衰竭15例.新中医.2005,37(1)：41-43.
[58]罗友根.丹参对油酸引起的急性肺损伤治疗作用的实验研究[J].河南职工医学院学报,2005,17(6)：328-329.
[59]陆健,张小虎,区永欣,古继红,田丙坤,.祛痰逐水法对实验性大鼠急性肺损伤的影响.中华中医药学刊,2008,26(06)：1347-1349.
[60]曹春水,黄亮.复方丹参对早期急性肺损伤炎性介质的影响[J].江西医药,2007,42(3)：208-211.
[61]刘红菊,陶晓南,辛建宝,等.中药热毒宁对急性肺损伤兔肺内致炎因子的影响.中国新药与临床杂志.2007,26(6)：446449.
[62]黄翠萍,杨和平,张珍祥.参麦注射液对脂多糖诱导大鼠急性肺损伤防护机制探讨[J].中华结核和呼吸杂志,2005,28(1)：67-68.
[63]赵晓琴,张剑锋,邝晓聪等.甘草酸二铵对急性肺损伤大鼠肺泡巨噬细胞白细胞介素10及18表达的影响[J].中华结核和呼吸杂志,2004,27(2)：126-127.
[64]李臣鸿,刘晓晴,张珍祥等.急性肺损伤时黄芪对核因子K13及白细胞介素6mRNA表达的影响[J].中华结核和呼吸杂志,2002,25(3)：189-190.
[65]田玉芝,陈瑞丰,杨俊山,等.胰炎合剂治疗大鼠急性坏死性胰腺炎肺损伤NF-KB活性的研究.中国中西医结合外科杂志.2007,13(2)：167-171.
[66]李建生,张卫红,赵君玫等.川芎嗪和参麦注射液对脑缺再灌注肺损伤老龄大鼠ATP酶和自由基代谢的影响[J].中国中西医结合急救杂志,2001,8(4)：210-211.
[67]曹慧玲,吕士杰,姜艳霞,等.急性肺损伤大鼠氧自由基变化及不同中药治疗作用的对比.中国中西医结合急救杂志.2006,13(3)：146-149.
[68]苏建玲,李星海,佟飞,等.银杏叶提取物对急性百草枯中毒大鼠肺过氧化损伤的保护作用[J].中华劳动卫生职业病杂志,2003,21(3)：226-227.
[69]耿耘.加减陷胸桃承汤合参麦针防治油酸型ARDS动物的实验观察[J].中国医药学报,2000,15(3)：34-36.
[70]阮秋蓉,宋建新,邓仲端等.山莨菪碱对血管内皮细胞组织因子和纤溶酶原激活物抑制剂1表达的影响及其机制研究[J].中国中西医结合杂志,2004,24(5)：422.
[71]王海峰,李建生,李素云,等.中医药治疗慢性呼吸衰竭研究进展.中国中医基础医学杂志,2010,16(12)：1191-1193.
[1]Global Initiative For Chronic Obstructive.Global strategy for diagnosis, management, and prevention of COPD [Internet] [updated 2009]. http://www.goldcopd.org.
[2]TSOUMAKIDOU M, TZANAKIS N, KYRIAKOU D, et al. Inflammatory cell profiles and T-lymphocyte subsets in chronic obstructive pulmonary disease and severe persistent asthma[J]. Clin Exp Allergy,2004,34(2):234-240.
[3]BARNES P J. Mediators of chronic obstructive pulmonary disease[J]. Pharmacol Rev,2004,56(4):515-548.
[4]QUINT J K, WEDZICHA J A. The neutrophil in chronic obstructive pulmonary disease[J]. J Allergy Clin Immunol, 2007,119(5):1065-1071.
[5]PROFITA M, SALA A, BONANNO A, et al. Chronic obstructive pulmonary disease and neutrophil infiltration:role of cigarette smoke and cyclooxygenase products[J]. Am J Physiol Lung Cell Mol Physiol,2010,298(2):L261-L269.
[6]SHAPIRO S D. The macrophage in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,1999,160(5 Pt 2):S29-S32.
[7]PONS J, SAULEDA J, FERRER J M, et al. Blunted gamma delta T-lymphocyte response in chronic obstructive pulmonary disease[J]. Eur Respir J,2005,25(3):441-446.
[8]TSAI J J, LIAO E C, HSU J Y, et al. The differences of eosinophil-and neutrophil-related inflammation in elderly allergic and non-allergic chronic obstructive pulmonary disease[J]. J Asthma,2010,47(9):1040-1044.
[9]VERMAELEN K, PAUWELS R. Pulmonary dendritic cells[J]. Am J Respir Crit Care Med,2005,172(5):530-551.
[10]BANCHEREAU J, STEINMAN R M. Dendritic cells and the control of immunityfJ]. Nature,1998,392(6673):245-252.
[11]COSIO M G, SAETTA M, AGUSTI A. Immunologic aspects of chronic obstructive pulmonary disease[J]. N Engl J Med, 2009,360(23):2445-2454.
[12]FINKELESTEIN R, FRASER R S, GHEZZO H, et al. Alveolar inflammation and its relation to emphysema in smokers[J]. Am J Respir Crit Care Med,1995,152(5 Pt 1):1666-1672.
[13]SAETTA M, DI STEFANO A, MAESTRELLI P, et al. Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis[J]. Am Rev Respir Dis,1993,147(2):301-306.
[14]TSOUMAKIDOU M, DEMEDTS I K, BRUSSELLE G G, et al. Dendritic cells in chronic obstructive pulmonary disease:new players in an old game[J]. Am J Respir Crit Care Med,2008,177(11):1180-1186.
[15]DEMOOR T, BRACKE K. R, VERMAELEN K Y, et al. CCR7 modulates pulmonary and lymph node inflammatory responses in cigarette smoke-exposed mice[J]. J Immunol,2009,183(12):8186-8194.
[16]BRACKE K, CATALDO D, MAES T, et al. Matrix metalloproteinase-12 and cathepsin D expression in pulmonary macrophages and dendritic cells of cigarette smoke-exposed mice[J]. Int Arch Allergy Immunol,2005,138(2):169-179.
[17]TZORTZAKI E G, SIAFAKAS N M. A hypothesis for the initiation of COPD[J]. Eur Respir J,2009,34(2):310-315.
[18]VASSALLO R, WALTERS P R, LAMONT J, et al. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study[J]. Respir Res,2010,11:45.
[19]FREEMAN C M, MARTINEZ FJ, HAN M K, et al. Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2009,180(12):1179-1188.
[20]TSOUMAKIDOU M, KOUTSOPOULOS A V, TZANAKIS N, et al. Decreased small airway and alveolar CD83+ dendritic cells in COPD[J]. Chest,2009,136(3):726-733.
[21]TSOUMAKIDOU M, BOULOUKAKI I, KOUTALA H, et al. Decreased sputum mature dendritic celis in healthy smokers and patients with chronic obstructive pulmonary disease[J]. Int Arch Allergy Immunol,2009,150(4):389-397.
[22]ROGERS A V, ADELROTH E, HATTOTUWA K, et al. Bronchial mucosal dendritic cells in smokers and ex-smokers with COPD:an electron microscopic study[J]. Thorax,2008,63(2):108-114.
[23]BROKAW J J, WHITE G W, BALUK P, et al. Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa[J]. Am J Respir Cell Mol Biol,1998,19(4):598-605.
[24]MARTORANA P A, LUNGHI B, LUCATTELLI M, et al. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice[J]. BMC Pulm Med,2008,8:17.
[25]LAMBRECHT B N, HAMMAD H. Lung dendritic cells:targets for therapy in allergic disease[J]. Handb Exp Pharmacol, 2009(188):99-114.
[26]GADGIL A, DUNCAN S R. Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2008,3(4):531-541.
[27]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2003,168(8):968-975.
[28]WOOLHOUSE I S, BAYLEYD L, STOCKLEY R A. Sputum chemotactic activity in chronic obstructive pulmonary disease: effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8[J]. Thorax, 2002,57(8):709-714.
[29]CROOKS S W, BAYLEY D L, HILL S L, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis:the role of leukotriene B4[J]. Eur Respir J,2000,15(2):274-280.
[30]Ko F W, LEUNG T F, WONG G W, et al. Measurement of tumor necrosis factor-alpha, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2009,4:79-86.
[31]PINTO-PLATA V M, LIVNAT G, GIRISH M, et al. Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD[J]. Chest,2007,131(1):37-43.
[32]BEEH K M, KORNMANN O, BUHL R, et al. Neutrophil chemotactic activity of sputum from patients with COPD:role of interleukin 8 and leukotriene B4[J]. Chest,2003,123(4):1240-1247.
[33]ZHANG Y, YANG S R, CHENG D Y. [The effect of glucocorticoid on IL-8 expressing in lung tissue of rat with chronic obstructive pulmonary disease][J]. Sichuan Da Xue Xue Bao Yi Xue Ban,2007,38(2):287-290.
[34]MILLER A L, STRIETER R M, GRUBER A D, et al. CXCR2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction[J]. J Immunol,2003,170(6):3348-3356.
[35]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2001,163(2):349-355.
[36]SULKOWSKA M, SULKOWSKI S, TERLIKOWSKI S, et al. Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type Ⅱ alveolar epithelial cells[J]. Pol J Pathol,1997,48(3):179-188.
[37]KEATINGS V M, COLLINS P D, SCOTT D M, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma[J]. Am J Respir Crit Care Med, 1996,153(2):530-534.
[38]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2001,163(2):349-355.
[39]CHURG A, WANG R D, TAI H, et al. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse[J]. Am J Respir Crit Care Med,2004,170(5):492-498.
[40]KARADAG F, KARUL A B, CILDAG O, et al. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD[J]. Lung,2008,186(6):403-409.
[41]WOOD AM, SIMMONDSM J, BAYLEY D L, et al. The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency[J]. Respir Res,2008,9:52.
[42]SAPEY E, WOOD A M, AHMAD A, et al. Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2010,182(2):192-199.
[43]RENNARD S I, FOGARTY C, KELSEN S, et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(9):926-934.
[44]DENTENER M A, CREUTZBERG E C, PENNINGS H J, et al. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease:a pilot study[J], Respiration,2008,76(3):275-282.
[45]SUISSA S, ERNST P, HUDSON M. TNF-alpha antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2008,21 (1):234-238.
[46]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[47]CULPITT S V, ROGERS D F, SHAH P, et al. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,167(1):24-31.
[48]RUSZNAK C, MILLS P R, DEVALIA J L, et al. Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol,2000,23(4):530-536.
[49]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[50]SINGH B, ARORA S, KHANNA V. Association of severity of COPD with IgE and interieukin-1 beta[J]. Monaldi Arch Chest Dis,2010,73(2):86-87.
[51]MAHAJAN B, VIJAYAN V K, AGARWAL M K, et al. Serum interleukin-1 beta as a marker for differentiation of asthma and chronic obstructive pulmonary disease[J]. Biomarkers,2008,13(7):713-727.
[52]DROEMANN D, GOLDMANN T, TIEDJE T, et al. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients[J]. Respir Res,2005,6:68.
[53]PONS J, SAULEDA J, REGUEIRO V, et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease[J]. Respir Res,2006,7:64.
[54]POLTORAK A, HE X, SMIRNOVA I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:mutations in Tlr4 gene[J]. Science,1998,282(5396):2085-2088.
[55]ZHANG X, SHAN P, JIANG G, et al. Toll-like receptor 4 deficiency causes pulmonary emphysema[J]. J Clin Invest, 2006,116(11):3050-3059.
[1]Global Initiative For Chronic Obstructive.Global strategy for diagnosis, management, and prevention of COPD [Internet] [updated 2009]. http://www.goldcopd.org.
[2]National Heart, Lung, and Blood Institute.2004 NHLBI morbidity and mortality chartbook on cardiovascular, lung and blood diseases [Internet]. Bethesda, MD:U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health [accessed 2007 Jul 26].[EB/OL]. http://www.nhlbi.nih.gov/resources/docs/cht-book.htm.
[3]LOPEZ A D, MURRAY C C. The global burden of disease,1990-2020[J]. Nat Med,1998,4(11):1241-1243.
[4]LOPEZ A D, SHIBUYA K, RAO C, et al. Chronic obstructive pulmonary disease:current burden and future projections[J]. Eur Respir J,2006,27(2):397-412.
[5]SEEMUNGAL T A, DONALDSON G C, BHOWMIK A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2000,161(5):1608-1613.
[6]KANNER R E, ANTHONISEN N R, CONNETT J E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease:results from the lung health study[J]. Am J Respir Crit Care Med,2001,164(3):358-364.
[7]MACNEE W. Acute exacerbations of COPD[J]. Swiss Med Wkly,2003,133(17-18):247-257.
[8]MCCRORY D C, BROWN C, GELFAND S E, et al. Management of acute exacerbations of COPD:a summary and appraisal of published evidence[J]. Chest,2001,119(4):1190-1209.
[9]CONNORS A J, DAWSON N V, THOMAS C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments)[J]. Am J Respir Crit Care Med,1996,154(4 Pt 1):959-967.
[10]GROENEWEGEN K H, SCHOLS A M, WOUTERS E F. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD[J]. Chest,2003,124(2):459-467.
[11]NEVINS M L, EPSTEIN S K. Predictors of outcome for patients with COPD requiring invasive mechanical ventilation[J]. Chest,2001,119(6):1840-1849.
[12]KANNER R E, ANTHONISEN N R, CONNETT J E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease:results from the lung health study[J]. Am J Respir Crit Care Med,2001,164(3):358-364.
[13]SCHUMAKER G L, EPSTEIN S K. Managing acute respiratory failure during exacerbation of chronic obstructive pulmonary disease[J]. Respir Care,2004,49(7):766-782.
[14]QUON B S, GAN W Q, SIN D D. Contemporary management of acute exacerbations of COPD:a systematic review and metaanalysis[J]. Chest,2008,133(3):756-766.
[15]KUNISAKI K. M, RICE K L, NIEWOEHNER D E. Management of acute exacerbations of chronic obstructive pulmonary disease in the elderly:an appraisal of published evidence[J]. Drugs Aging,2007,24(4):303-324.
[16]有创-无创序贯机械通气多中心研究协作组.以肺部感染控制窗为切换点行有创与无创序贯机械通气治疗慢性阻塞性肺疾病所致严重呼吸衰竭的随机对照研究[J].中华结核和呼吸杂志,2006(1)：14-18.
[17]SENEFF M G, WAGNER D P, WAGNER R P, et al. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease[J]. JAMA, 1995,274(23):1852-1857.
[18]石占利,方堃,李国辉,等.通腑法对慢性阻塞性肺疾病呼吸衰竭患者呼吸力学及气道炎症因子的影响[J].中华中医药杂志,2010(10).1710-1713.
[19]石占利,方堃,李国辉,等.通腑法对慢性阻塞性肺疾病呼吸衰竭患者胃肠激素水平的干预作用[J].中华中医药学刊,2010(4).815-817.
[20]兰万成,曾靖,罗翌.中西医结合治疗慢性阻塞性肺疾病急性发作期呼吸衰竭的临床观察[J].辽宁中医杂志,2010(2).310-312.
[21]韩云,张燕,谢东平,等.中医调肠法配合无创通气治疗AECOPD呼吸衰竭的临床研究[J].中国中西医结合杂志,2010(8).814-818.
[22]李秀彦.通腑降浊法治疗慢性阻塞性肺疾病呼吸衰竭的疗效观察[J].河北中医,2006(7)：503-504.
[23]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,168(8):968-975.
[24]FUJIMOTO K, YASUO M, URUSHIBATA K, et al. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease[J]. Eur Respir J,2005,25(4):640-646.
[25]PAPI A, BELLETTATO C M, BRACCIONI F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations[J]. Am J Respir Crit Care Med,2006,173(10):1114-1121.
[26]GERN J E, FRENCH D A, GRINDLE K A, et al. Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells[J]. Am J Respir Cell Mol Biol,2003,28(6):731-737.
[27]MERCER P F, SHUTE J K, BHOWMIK. A, et al. MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation[J]. Respir Res,2005,6:151.
[28]FIORENZA D, VIGLIO S, LUPI A, et al. Urinary desmosine excretion in acute exacerbations of COPD:a preliminary report[J]. Respir Med,2002,96(2):110-114.
[29]FRANCIOSI L G, PAGE C P, CELI B R, et al. Markers of exacerbation severity in chronic obstructive pulmonary disease[J]. Respir Res,2006,7:74.
[30]ZHU J, MAJUMDAR S, QIU Y, et al. Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells[J]. Am J Respir Crit Care Med,2001,164(12):2220-2228.
[31]BHOWMIK A, SEEMUNGAL T A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations[J]. Thorax,2000,55(2):114-120.
[32]CARPAGNANO G E, RESTA O, FOSCHINO-BARBARO M P, et al. Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease:effect of carbocysteine lysine salt monohydrate (SCMC-Lys)[J]. Eur J Pharmacol,2004,505(1-3):169-175.
[33]CHAUDHURI N, DOWER S K, WHYTE M K, et al. Toll-like receptors and chronic lung disease[J]. Clin Sci (Lond),2005,109(2):125-133.
[34]GERRITSEN W B, ASIN J, ZANEN P, et al. Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients[J]. Respir Med,2005,99(1):84-90.
[35]BIERNACKI W A, KHARITONOV S A, BARNES P J. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD[J]. Thorax,2003,58(4):294-298.
[36]BHOWMIK A, SEEMUNGAL T A, DONALDSON G C, et al. Effects of exacerbations and seasonality on exhaled nitric oxide in COPD[J]. Eur Respir J,2005,26(6):1009-1015.
[37]HURST J R, DONALDSON G C, PERERA W R, et al. Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2006,174(8):867-874.
[38]ANTONESCU-TURCU A L, TOMIC R. C-reactive protein and copeptin:prognostic predictors in chronic obstructive pulmonary disease exacerbations[J]. Curr Opin Pulm Med,2009,15(2):120-125.
[39]RAMMAERT B, VERDIER N, CAVESTRI B, et al. Procalcitonin as a prognostic factor in severe acute exacerbation of chronic obstructive pulmonary disease[J]. Respirology,2009,14(7):969-974.
[40]GERRITSEN W B, ASIN J, ZANEN P, et al. Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients[J]. Respir Med,2005,99(1):84-90.
[41]CREUTZBERG E C, WOUTERS E F, VANDERHOVEN-AUGUSTIN I M, et al. Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2000,162(4 Pt 1):1239-1245.
[42]DROST E M, SKWARSKI K M, SAULEDA J, et al. Oxidative stress and airway inflammation in severe exacerbations of COPD[J]. Thorax,2005,60(4):293-300.
[43]MAEDER M T, BRUTSCHE M H, CHRIST A, et al. Natriuretic peptides for the prediction of severely impaired peak VO2 in patients with lung disease[J]. Respir Med,2009,103(9):1337-1345.
[44]张九进,陈显源,邓海波,等.慢性阻塞性肺疾病患者血浆p-内啡肽水平与呼吸功能的相关性研究[J].实用医学杂志,2003,19(1).39-40.
[45]BARNES P J, CHOWDHURY B, KHARITONOV S A, et al. Pulmonary biomarkers in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2006,174(1):6-14.
[46]李建生.中医药治疗慢性阻塞性肺疾病研究的实践与若干思考[J].河南中医,2065(5)：13-15.
[47]朱文锋.中医内科疾病诊疗常规[M].长沙：湖南科技出版社,1999.
[48]郑筱萸.中药新药临床研究指导原则试行[M].北京：中国医药科技出版社,2002.
[49]王永炎,晃恩祥.今日中医内科中卷[M].北京：人民卫生出版社,2000.
[50]ANTHONISEN N R, MANFREDA J, WARREN C P, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease[J]. Ann Intern Med,1987,106(2):196-204.
[51]CELLI B R, MANNEE W. Standards for the diagnosis and treatment of patients with COPD:a summary of the ATS/ERS position paper[J]. Eur Respir J,2004,23(6):932-946.
[52]PAPI A, BELLETTATO C M, BRACCIONI F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations[J]. Am J Respir Crit Care Med,2006,173(10):1114-1121.
[53]SETHI S, EVANS N, GRANT B J, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease[J]. N Engl J Med,2002,347(7):465-471.
[54]WEDZICHA J A. Role of viruses in exacerbations of chronic obstructive pulmonary disease[J]. Proc Am Thorac Soc,2004,1(2):115-120.
[55]WILKINSON T M, DONALDSON G C, JOHNSTON S L, et al. Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2006,173(8):871-876.
[56]MELONI F, PASCHETTO E, MANGIAROTTI P, et al. Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations[J]. J Chemother,2004,16(1):70-76.
[57]LIEBERMAN D, LIEBERMAN D, BEN-YAAKOV M, et al. Infectious etiologies in acute exacerbation of COPD[J]. Diagn Microbiol Infect Dis,2001,40(3):95-102.
[58]MACNEE W, DONALDSON K. Exacerbations of COPD:environmental mechanisms[J]. Chest,2000,117(5 Suppl 2):390S-397S.
[59]RUTTEN F H, CRAMER M J, LAMMERS J W, et al. Heart failure and chronic obstructive pulmonary disease: An ignored combination?[J]. Eur J Heart Fail,2006,8(7):706-711.
[60]ABROUG F, OUANES-BESBES L, NCIRI N, et al. Association of left-heart dysfunction with severe exacerbation of chronic obstructive pulmonary disease:diagnostic performance of cardiac biomarkers[J]. Am J Respir Crit Care Med,2006,174(9):990-996.
[61]BASTIN A J, STARLING L, AHMED R, et al. High prevalence of undiagnosed and severe chronic obstructive pulmonary disease at first hospital admission with acute exacerbation[J]. Chron Respir Dis, 2010,7(2):91-97.
[62]CONNORS A J, DAWSON N V, THOMAS C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments) [J]. Am J Respir Crit Care Med,1996,154(4 Pt 1):959-967.
[63]TILLIE-LEBLOND I, MARQUETTE C H, PEREZ T, et al. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease:prevalence and risk factors[J]. Ann Intern Med, 2006,144(6):390-396.
[64]DAHL M. Biomarkers for chronic obstructive pulmonary disease:surfactant protein D and C-reactive protein[J]. Am J Respir Crit Care Med,2008,177(11):1177-1178.
[65]DAHL M, VESTBO J, LANGE P, et al. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(3):250-255.
[66]DAHL M, VESTBO J, ZACHO J, et al. C reactive protein and chronic obstructive pulmonary disease:a Mendelian randomisation approach[J]. Thorax,2011,66(3):197-204.
[67]RAMMAERT B, VERDIER N, CAVESTRI B, et al. Procalcitonin as a prognostic factor in severe acute exacerbation of chronic obstructive pulmonary disease[J]. Respirology,2009,14(7):969-974.
[68]SHAKOORI T A, SIN D D, GHAFOOR F, et al. Serum surfactant protein D during acute exacerbations of chronic obstructive pulmonary disease[J]. Dis Markers,2009,27(6):287-294.
[69]李建生.慢性阻塞性肺疾病中医辨证治疗概要[J].河南中医学院学报,2009(4)：9-11.
[70]李建生.关于慢性呼吸衰竭中医诊断及辨证治疗标准的研究[J].中医学报,2010(4)：627-629.
[71]ANTHONISEN N R, WRIGHT E C. Bronchodilator response in chronic obstructive pulmonary disease[J]. Am Rev Respir Dis,1986,133(5):814-819.
[72]CHANGE J H, LEE J H, KIM M K, et al. Determinants of respiratory symptom development in patients with chronic airflow obstruction[J]. Respir Med,2006,100(12):2170-2176.
[73]李建生,王至婉,余学庆,等.中药治疗慢性阻塞性肺疾病稳定期的系统评价[J].辽宁中医杂志,2010,37(2).229-231.
[74]KNAUS W A, DRAPER E A, WAGNER D P, et al. APACHE Ⅱ:a severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[75]KNAUS W A, DRAPER E A, WAGNER D P, et al. APACHE Ⅱ:a severity of disease classification system[J]. Crit Care Med,1985,13(10):818-829.
[76]GOEL A, PINCKNEY R G, LITTENBERG B. APACHE II predicts long-term survival in COPD patients admitted to a general medical ward[J]. J Gen Intern Med,2003,18(10):824-830.
[77]RANIERI P, BIANCHETTI A, MARGIOTTA A, et al. Predictors of 6-month mortality in elderly patients with mild chronic obstructive pulmonary disease discharged from a medical ward after acute nonacidotic exacerbation[J]. J Am Geriatr Soc,2008,56(5):909-913.
[78]RANIERI P, BIANCHETTI A, MARGIOTTA A, et al. Predictors of 6-month mortality in elderly patients with mild chronic obstructive pulmonary disease discharged from a medical ward after acute nonacidotic exacerbation[J]. J Am Geriatr Soc,2008,56(5):909-913.
[79]AYDOGDU M, GURSEL G. Does admission from different sources have any influence on intensive care unit outcome in COPD patients?[J]. Tuberk Toraks,2008,56(4):375-381.
[80]GURSEL G. Determinants of the length of mechanical ventilation in patients with COPD in the intensive care unit[J]. Respiration,2005,72(1):61-67.
[81]连增志,穆传勇,黄建安APACHEⅡ评分与临床肺部感染评分在AECOPD中的应用比较分析[J].临床肺科杂志,2009,14(11).1463-1465.
[82]BARNES P J. New molecular targets for the treatment of neutrophilic diseases[J]. J Allergy Clin Immunol, 2007,119(5):1055-1062,1063-1064.
[83]SINGH D, EDWARDS L, TAL-SINGER R, et al. Sputum neutrophils as a biomarker in COPD:findings from the ECLIPSE study[J]. Respir Res,2010,11:77.
[84]TETLEY T D. Macrophages and the pathogenesis of COPD[J]. Chest,2002,121(5 Suppl):156S-159S.
[85]SHAPIRO S D. Evolving concepts in the pathogenesis of chronic obstructive pulmonary disease[J]. Clin Chest Med,2000,21(4):621-632.
[86]Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party[J]. Lancet, 1981,1(8222):681-686.
[87]Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease:a clinical trial. Nocturnal Oxygen Therapy Trial Group[J]. Ann Intem Med,1980,93(3):391-398.
[88]FLETCHER C M. The clinical diagnosis of pulmonary emphysema; an experimental study[J]. Proc R Soc Med,1952,45(9):577-584.
[89]FLETCHER C M, ELMES P C, FAIRBAIRN A S, et al. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population[J]. Br Med J,1959,2(5147):257-266.
[90]MAHLER D A, WELLS C K. Evaluation of clinical methods for rating dyspnea[J]. Chest, 1988,93(3):580-586.
[91]Dyspnea. Mechanisms, assessment, and management:a consensus statement. American Thoracic Society[J]. Am J Respir Crit Care Med,1999,159(1):321-340.
[92]LIN Y X, Xu W N, LIANG L R, et al. The cross-sectional and longitudinal association of the BODE index with quality of life in patients with chronic obstructive pulmonary disease[J]. Chin Med J (Engl), 2009,122(24):2939-2944.
[93]PALADINI L, HODDER R, CECCHINI I, et al. The MRC dyspnoea scale by telephone interview to monitor health status in elderly COPD patients[J]. Respir Med,2010,104(7):1027-1034.
[94]TSIMOGIANNI A M, PAPIRIS S A, STATHOPOULOS G T, et al. Predictors of outcome after exacerbation of chronic obstructive pulmonary disease[J]. J Gen Intern Med,2009,24(9):1043-1048.
[95]NISHIMURA K, IZUMI T, TSUKINO M, et al. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD[J]. Chest,2002,121(5):1434-1440.
[96]O'SHAUGHNESSY T C, ANSARI T W, BARNES N C, et al. Inflammation in bronchial biopsies of subjects with chronic bronchitis:inverse relationship of CD8+ T lymphocytes with FEV1[J]. Am J Respir Crit Care Med, 1997,155(3):852-857.
[97]MUELLER R, CHANEZ P, CAMPBELL A M, et al. Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis[J]. Respir Med,1996,90(2):79-85.
[98]SAETTA M, BARALDO S, TURATO G, et al. Increased proportion of CD8+ T-lymphocytes in the paratracheal lymph nodes of smokers with mild COPD[J]. Sarcoidosis Vase Diffuse Lung Dis,2003,20(1):28-32.
[99]DE JONG.J W, VAN DER BELT-GRITTER B, KOETER G H, et al. Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease:association with smoking, IgE and lung function[J]. Respir Med,1997,91(2):67-76.
[100]CARAMORI G, ROMAGNOLI M, CASOLARI P, et al. Nuclear localisation of p65 in sputum macrophages but not in sputum neutrophils during COPD exacerbations[J]. Thorax,2003,58(4):348-351.
[101]DO STEFANO A, CARAMORI G, OATES T, et al. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD[J]. Eur Respir J,2002,20(3):556-563.
[102]CHAPCVAL S P, AL-GARAWI A, LORA J M, et al. Inhibition of NF-kappaB activation reduces the tissue effects of transgenic IL-13[J]. J Immunol,2007,179(10):7030-7041.
[103]SADIKOT R T, ZENG H, JOO M, et al. Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa[J]. J Immunol,2006,176(8):4923-4930.
[104]LORA J M, ZHANGD M, LIAO S M, et al. Tumor necrosis factor-alpha triggers mucus production in airway epithelium through an IkappaB kinase beta-dependent mechanism[J]. J Biol Chem, 2005,280(43):36510-36517.
[105]SATO S, NOMURAF F, KAWAI T, et al. Synergy and cross-tolerance between toll-like receptor (TLR) 2-and TLR4-mediated signaling pathways[J]. J Immunol,2000,165(12):7096-7101.
[106]NOMURA F, AKASHI S, SAKAO Y, et al. Cutting edge:endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface toll-like receptor 4 expression[J]. J Immunol, 2000,164(7):3476-3479.
[107]SABROE I, JONES E C, USHER L R, et al. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes:a critical role for monocytes in leukocyte lipopolysaccharide responses[J]. J Immunol, 2002,168(9):4701-4710.
[108]PRINCE L R, ALLEN L, JONES E C, et al. The role of interleukin-lbeta in direct and toll-like receptor 4-mediated neutrophil activation and survival[J]. Am J Pathol,2004,165(5):1819-1826.
[109]DROEMANN D, GOLDMANN T, TIEDJE T, et al. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients[J]. Respir Res,2005,6:68.
[110]PONS J, SAULEDA J, REGUEIRO V, et al. Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease[J]. Respir Res,2006,7:64.
[111]POLTORAK A, HE X, SMIRNOVA I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene[J]. Science,1998,282(5396):2085-2088.
[112]ZHANG X, SHAN P, JJIANG G, et al. Toll-like receptor 4 deficiency causes pulmonary emphysema[J]. J Clin Invest,2006,116(11):3050-3059.
[113]VOLANAKIS J E. Human C-reactive protein:expression, structure, and function[J]. Mol Immunol, 2001,38(2-3):189-197.
[114]DE TORRES J P, CORDOBA-LANUS E, LOPEZ-AGUILAR C, et al. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients[J]. Eur Respir J,2006,27(5):902-907.
[115]GAN W Q, MAN S F, SIN D D. The interactions between cigarette smoking and reduced lung function on systemic inflammation[J]. Chest,2005,127(2):558-564.
[116]THORLEIFSSON S J, MARGRETARDOTTIR O B, GUDMUNDSSON G, et al. Chronic airflow obstruction and markers of systemic inflammation:results from the BOLD study in Iceland[J]. Respir Med, 2009,103(10):1548-1553.
[117]OMORI H, TSUJI M, SATAt K, et al. Correlation of C-reactive protein with disease severity in CT diagnosed emphysema[J]. Respirology,2009,14(4):551-558.
[118]MAN S F, XING L, CONNETT J E, et al. Circulating fibronectin to C-reactive protein ratio and mortality:a biomarker in COPD?[J]. Eur Respir J,2008,32(6):1451-1457.
[119]KARADAG F, KIRDAR S, KARUL A B, et al. The value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease[J]. Eur J Intern Med,2008,19(2):104-108.
[120]DANIELS J M, SCHOORL M, SNUDERS D, et al. Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD[J]. Chest,2010,138(5):1108-1115.
[121]PERERA W R, HURST J R, WILKINSON T M, et al. Inflammatory changes, recovery and recurrence at COPD exacerbation[J]. Eur Respir J,2007,29(3):527-534.
[122]RUIZ-GONZALEZ A, LACASTA D, IBARZ M, et al. C-reactive protein and other predictors of poor outcome in patients hospitalized with exacerbations of chronic obstructive pulmonary disease[J]. Respirology, 2008,13(7):1028-1033.
[123]TSUNODA K, DOUGE K, AKIYA Y, et al. Beta-endorphin secretion at the time of sudden death due to cardiac or respiratory failure[J]. Nihon Hoigaku Zasshi,1992,46(3):182-188.
[124]NGAIS P, JONES A Y, HUI-CHAN C W, et al. Effect of 4 weeks of Acu-TENS on functional capacity and beta-endorphin level in subjects with chronic obstructive pulmonary disease:a randomized controlled trial[J]. Respir Physiol Neurobiol,2010,173(1):29-36.
[125]MAHLER D A, MURRAY J A, WATERMAN L A, et al. Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD[J]. Eur Respir J,2009,33(4):771-777.
[126]张九进,陈显源,邓海波,等.慢性阻塞性肺疾病患者血浆β-内啡肽水平与呼吸功能的相关性研究[J].实用医学杂志,2003,19(1).39-40.
[127]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[128]CULPiTT S V, ROGERS D F, SHAH P, et al. Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2003,167(1):24-31.
[129]RUSZNAK C, MILLS P R, DEVALIA J L, et al. Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol,2000,23(4):530-536.
[130]SAPEY E, AHMAD A, BAYLEY D, et al. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD[J]. J Clin Immunol,2009,29(4):508-516.
[131]SINGH B, ARORAS, KHANNA V. Association of severity of COPD with IgE and interleukin-1 beta[J]. Monaldi Arch Chest Dis,2010,73(2):86-87.
[132]MAHAJAN B, VUAYAN V K, AGARWAL M K, et al. Serum interleukin-1beta as a marker for differentiation of asthma and chronic obstructive pulmonary disease[J]. Biomarkers,2008,13(7):713-727.
[133]ALDONYTE R, JANSSON L, PIITULAINEN E, et al. Circulating monocytes from healthy individuals and COPD patients[J]. Respir Res,2003,4:11.
[134]BOLTON C E, EVANS M, IONESCU A A, et al. Insulin resistance and inflammation-A further systemic complication of COPD[J]. COPD,2007,4(2):121-126.
[135]BARNES P J, CELLI B R. Systemic manifestations and comorbidities of COPD[J]. Eur Respir J, 2009,33(5):1165-1185.
[136]CHAOUAT A, SAVALE L, CHOUAID C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension[J]. Chest,2009,136(3):678-687.
[137]K.UHN C R, HOMER R J, ZHU Z, et al. Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung[J]. Am J Respir Cell Mol Biol,2000,22(3):289-295.
[138]BHOWMIK A, SEEMUNGALT A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations [J]. Thorax,2000,55(2):114-120.
[139]BHOWMIK A, SEEMUNGAL T A, SAPSFORD R J, et al. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations[J]. Thorax,2000,55(2):114-120.
[140]SONG W, ZHAO J, LI Z. Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD[J]. Chin Med J (Engl),2001,114(11):1140-1142.
[141]BUCCHIONI E, KHARITONOV S A, ALLEGRA L, et al. High levels of interleukin-6 in the exhaled breath condensate of patients with COPD[J]. Respir Med,2003,97(12):1299-1302.
[142]DEBIGARE R, MARQUIS K, COTE C H, et al. Catabolic/anabolic balance and muscle wasting in patients with COPD[J]. Chest,2003,124(1):83-89.
[143]GODOY I, CAMPANA A O, GERALDO R R, et al. Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients[J]. Eur Respir J,2003,22(6):920-925.
[144]HAGEMAN G J, LARIK I, PENNINGS H J, et al. Systemic poly(ADP-ribose) polymerase-1 activation, chronic inflammation, and oxidative stress in COPD patients[J]. Free Radic Biol Med,2003,35(2):140-148.
[145]WEDZICHA J A, SEEMUNGAL T A, MACCALLUM P K, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels[J]. Thromb Haemost,2000,84(2):210-215.
[146]PINTO-PLATA V M, LIVNAT G, GIRISH M, et al. Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD[J]. Chest,2007,131(1):37-43.
[147]WALTER R E, WILK J B, LARSON M G, et al. Systemic inflammation and COPD:the Framingham Heart Study[J]. Chest,2008,133(1):19-25.
[148]SIN D D, MAN S F, MARCINIUK D D, et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2008,177(11):1207-1214.
[149]QIU Y, ZHU J, BANDI V, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2003,168(8):968-975.
[150]WOOLHOUSE I S, BAYLEY D L, STOCKLEY R A. Sputum chemotactic activity in chronic obstructive pulmonary disease:effect of alpha(1)-antitrypsin deficiency and the role of leukotriene B(4) and interleukin 8[J]. Thorax,2002,57(8):709-714.
[151]CROOKS S W, BAYLEY D L, HILL S L, et al. Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis:the role of leukotriene B4[J]. Eur Respir J,2000,15(2):274-280.
[152]KO F W, LEUNG T F, WONG G W, et al. Measurement of tumor necrosis factor-alpha, leukotriene B4, and interleukin 8 in the exhaled breath condensate in patients with acute exacerbations of chronic obstructive pulmonary disease[J]. Int J Chron Obstruct Pulmon Dis,2009,4:79-86.
[153]BEEH K M, KORNMANN O, BUHL R, et al. Neutrophil chemotactic activity of sputum from patients with COPD:role of interleukin 8 and leukotriene B4[J]. Chest,2003,123(4):1240-1247.
[154]ZHANG Y, YANG S R, CHENG D Y. [The effect of glucocorticoid on IL-8 expressing in lung tissue of rat with chronic obstructive pulmonary disease][J]. Sichuan Da Xue Xue Bao Yi Xue Ban, 2007,38(2):287-290.
[155]MILLER A L, STRIETER R M, GRUBER A D, et al. CXCR2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction[J]. J Immunol,2003,170(6):3348-3356.
[156]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2001,163(2):349-355.
[157]SULKOWSKA M, SULKOWSKI S, TERLIKOWSKI S, et al. Tumor necrosis factor-alpha induces emphysema-like pulmonary tissue rebuilding. Changes in type II alveolar epithelial cells[J]. Pol J Pathol, 1997,48(3):179-188.
[158]KEATINGS V M, COLLINS P D, SCOTT D M, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma[J]. Am J Respir Crit Care Med,1996,153(2):530-534.
[159]AARON S D, ANGEL J B, LUNAU M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2001,163(2):349-355.
[160]CHURG A, WANG R D, TAI H, et al. Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse[J]. Am J Respir Crit Care Med,2004,170(5):492-498.
[161]KARADAG F, KARUL A B, CILDAG O, et al. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD[J]. Lung,2008,186(6):403-409.
[162]WOOD A M, SIMMONDS M J, BAYLEY D L, et al. The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency [J]. Respir Res,2008,9:52.
[163]SAPEY E, WOOD A M, AHMAD A, et al. Tumor necrosis factor-{alpha} rs361525 polymorphism is associated with increased local production and downstream inflammation in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2010,182(2):192-199.
[164]RENNARD S I, FOGARTY C, KELSEN S, et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2007,175(9):926-934.
[165]DENGENER M A, CREUTZBERG E C, PENNINGS H J, et al. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease:a pilot study[J]. Respiration,2008,76(3):275-282.
[166]SUISSA S, ERNST P, HUDSON M. TNF-alpha antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease[J]. Pulm Pharmacol Ther,2008.21(1):234-238.
[167]KUMAR R K, WEBB D C, HERBERT C, et al. Interferon-gamma as a possible target in chronic asthma[J]. Inflamm Allergy Drug Targets,2006,5(4):253-256.
[168]COSIO M G, GUERASSIMOV A. Chronic obstructive pulmonary disease. Inflammation of small airways and lung parenchyma[J]. Am J Respir Crit Care Med,1999,160(5 Pt 2):S21-S25.
[169]WANG X Q, PANOUSIS C G, ALFARO M L, et al. Interferon-gamma-mediated downregulation of cholesterol efflux and ABC1 expression is by the Statl pathway[J]. Arterioscler Thromb Vasc Biol,2002,22(5):e5-e9.
[170]ELIAS J A, KANG M J, CROTHERS K, et al. State of the art. Mechanistic heterogeneity in chronic obstructive pulmonary disease:insights from transgenic mice[J]. Proc Am Thorac Soc,2006,3(6):494-498.
[171]TZANAKIS N, CHRYSOFAKIS G, TSOUMAKIDOU M, et al. Induced sputum CD8+ T-lymphocyte subpopulations in chronic obstructive pulmonary disease[J]. Respir Med,2004,98(l):57-65.
[172]SZABO S J, SULLIVAN B M, STEMMANN C, et al. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells[J]. Science,2002,295(5553):338-342.
[173]DI STEFANO A, CARAMORI G, CAPELLI A, et al. STAT4 activation in smokers and patients with chronic obstructive pulmonary disease[J]. Eur Respir J,2004,24(l):78-85.