特发性肺纤维化患者肺泡灌洗液及血清中白细胞介素4、12水平变化的意义

目的探讨特发性肺纤维化（IPF）患者肺泡灌洗液及血清中自细胞介素4、12（IL-4、IL-12）水平变化的意义。方法用酶联免疫吸附法，检测30例IPF患者（IPF组）血清及支气管肺泡灌洗液（BALF）中IL-4、IL-12的水平；健康非吸烟的自愿献血者30名，为血清对照组，检测其血清IL4、IL-12的水平；以胸痛为主诉进行BALF检查证实为健康者9名，作为BALF对照组，检测其BALF中IL-4、IL-12的水平。结果IPF组患者BALF中IL-4为（84．87±26．10）pg／ml、IL-12为（12．33±6．89）pg／ml，对照组BALF中IL-4、IL-12分别为（55．78±22．88）、（46．674-24．67）pg／ml，两组相比差异有显著意义（P值均〈0．01）；IPF组患者血清IL-4水平的变化与BLAF一致，但血清IL-12为（45．70±25．65）pg／ml，与血清对照组（46．80±23．73）pg／ml相比差异无显著性（P〉0．05）。结论IPF时Th1型细胞因子IL-12水平下降主要发生在肺组织局部，而Th2型细胞因子IL-4水平增高的变化是一种全身性行为，TH1／Th2型细胞因子平衡失调，在IPF的发生、发展过程中起着重要的作用。     

肺结节病患者支气管肺泡灌洗液中细胞因子水平的变化

为探讨细胞因子在肺结节病发病机制中的作用，本研究检测了肺结节病患者支气管肺泡灌洗液(BALF)中白细胞介素(IL)-13和肿瘤坏死因子(TNFα)水平，现报告如下。     

特发性肺纤维化患者肺泡灌洗液及血清中前列腺素E2和白细胞介素12、13水平变化的意义

目的　探讨特发性肺纤维化 (IPF)患者肺泡灌洗液及血清中前列腺素E2 (PGE2 )和白细胞介素 12、13(IL 12、IL 13)水平变化的意义。方法　用放射免疫法及酶联免疫吸附法 ,检测 30例IPF患者 (IPF组 )血清及支气管肺泡灌洗液 (BALF)中PGE2 和IL 12、IL 13的水平 ;健康非吸烟的自愿献血者 30名 ,为血清对照组 ,检测其血清PGE2 和IL 12、IL 13的水平 ;以胸痛为主诉进行BALF检查证实为健康者 9名 ,作为BALF对照组 ,检测其BALF中PGE2 和IL 12、IL 13的水平。结果　IPF组患者BALF中PGE2 为 (5 91± 88)ng/L、IL 12为 (1 34± 0 2 5 )ng/L、IL 13为 (38± 5 )ng/L ,对照组BALF中PGE2 、IL 12、IL 13分别为 (2 38± 7)、(2 2 9± 0 2 6 )、(2 0± 4 )ng/L ,两组相比差异有显著意义 (P值均 <0 0 1) ;血清IL 13水平的变化与BLAF一致 ,但IPF组患者血清PGE2 为 (2 35± 13)ng/L、IL 12为 (2 35± 0 14 )ng/L ,与血清对照组相比差异无显著性 (P >0 0 5 )。结论　IPF患者BALF中PGE2 水平升高 ,可能与IL 13的增高和IL 12水平的下降有关 ,并在IPF的发生、发展中起重要的作用。肺纤维化患者PGE2水平增高主要发生在肺的局部 ,而并非全身性的。     

特发性肺纤维化患者肺泡灌洗液及血清中自细胞介素4、12水平变化的意义

目的 探讨特发性肺纤维化(IPF)患者肺泡灌洗液及血清中自细胞介素4、12(IL-4,IL-12)水平变化的意义.方法 用酶联免疫吸附法,检测30例IPF患者(IPF组)血清及支气管肺泡灌洗液(BALF)中IL-4、IL-12的水平;健康非吸烟的自愿献血者30名,为血清对照组,检测其血清IL-4、IL-12的水平;以胸痛为主诉进行BALF检查证实为健康者9名.作为BALF对照组,检测其BALF中IL-4、IL-12的水平.结果 IPF组患者BALF中IL-4为(84.87±26.10)pg/ml、IL-12为(12.33±6.89)pg/ml,对照组BALF中IL-4、IL-12分别为(55.78± 22.88)、(46.67±24.67)pg/ml,两组相比差异有显著意义(P值均＜0.01);IPF组患者血清IL-4水平的变化与BLAF一致,但血清IL-12为(45.70±25.65)pg/ml,与血清对照组(46.80±23.73)pg/ml相比差异无显著性(P＞0.05).结论 IPF时Th1型细胞因子IL-12水平下降主要发生在肺组织局部,而Th2型细胞因子IL-4水平增高的变化是一种全身性行为,TH1/Th2型细胞因子平衡失调,在IPF的发生、发展过程中起着重要的作用.     

特发性肺纤维化患者血清及支气管肺泡灌洗液中KL-6水平及其意义

特发性肺纤维化（IPF）发病隐袭，机制不明，预后差。KL-6是Ⅱ型肺泡上皮细胞膜上的一种糖蛋白，可从Ⅱ型肺泡上皮细胞上脱落进入肺泡腔和血液。有报道，KL-6可用来监测肺纤维化的活动早期发现IPF病情变化。本研究通过检测IPF患者血清及支气管肺泡灌洗液（BALF）中KL-6水平，探讨其在IPF诊断、监测中的应用价值。     

肺结节病患者支气管肺泡灌洗液中白细胞介素-2及其可溶性受体的表达

肺结节病下呼吸道的表现为淋巴细胞性肺泡炎 ,支气管肺泡灌洗液 (ＢＡＬＦ)中ＣＤ4 /ＣＤ8 比值增高 ;ＣＤ4 细胞不仅数量增加而且功能活跃 ;肺组织中Ⅰ型Ｔ辅助细胞 (Ｔｈ1)占优势[1] 。但对血清和ＢＡＬＦ中白细胞介素 (ＩＬ) 2的研究结果不尽相同[2 ,3] ,更缺乏对可溶性ＩＬ 2受体 (ｓＩＬ 2Ｒ)的同步研究。本研究同步测定了肺结节病患者ＢＡＬＦ中ＩＬ 2和ｓＩＬ 2Ｒ水平 ,探讨其在发病机制中的作用。一、对象与方法1.对象 :结节病组 :11例 ,男 4例 ,女 7例 ,年龄 2 3～ 49岁 ,诊断符合 1993年中华医学会呼吸病学分会第三次修订的结…     

支气管肺泡灌洗液中IL-10的检测对肺结核的诊断意义

目的检测肺结核患者支气管肺泡灌洗液中IL-10水平,探索IL-10对肺结核的诊断意义。方法采用ELISA双抗体夹心法测定50例肺结核患者及48名健康体检者外周血IL-10水平,同时测定肺结核患者抗结核治疗前后支气管肺泡灌洗液中IL-10水平,观察其差异有无统计学意义。结果肺结核患者外周血中IL-10水平明显高于健康对照组,肺结核患者经抗结核治疗后外周血和支气管肺泡灌洗液中IL-10水平均较治疗前下降。结论在结核病的发生过程中IL-10发挥了重要的免疫抑制作用,它对临床上肺结核的诊断有一定辅助意义。     

特发性肺纤维化病人支气管肺泡灌洗液中细胞外基质的变化

为探讨细胞外基质在肺纤维化中的作用，检测了１３例特发性肺纤维化（ＩＰＦ）病人和１１例正常人支气管肺泡灌洗液（ＢＡＬＦ）和外周血中纤维连接素（ＦＮ）、透明质酸（ＨＡ）和Ⅲ型前胶原（ＰＣⅢ）水平。结果：（１）ＩＰＦ组ＢＡＬＦ中ＦＮ、ＨＡ和ＰＣⅢ水平分别较外周血明显升高，并且也分别高于对照组ＢＡＬＦ中的水平；（２）ＩＰＦ组ＢＡＬＦ中的ＦＮ和ＨＡ均分别与细胞总数和中性粒细胞数（％）呈正相关，而ＰＣⅢ与肺泡巨噬细胞总数呈正相关。另外，ＦＮ、ＨＡ、ＰＣⅢ之间均呈明显的正相关。结果提示：ＩＰＦ病人肺内ＦＮ、ＨＡ和ＰＣⅢ产生增多；ＢＡＬＦ中ＦＮ、ＨＡ和ＰＣⅢ的水平从不同侧面反映了疾病活动性并具有估计预后的作用。     

特发性肺纤维化患者支气管肺泡灌洗液和血清基质金属蛋白酶及其抑制剂检测

目的探讨特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)及血清中基质金属蛋白酶9(MMP9)、基质金属蛋白酶组织抑制剂1(TIMP1)水平的变化。方法2001至2004年用酶联免疫吸附(ELISA)法检测30例IPF患者BALF及血清中MMP9和TIMP1的水平,同时行肺高分辨率CT(HRCT)及肺功能检查。健康非吸烟的自愿献血者30名,为血清对照组。以胸痛为自觉症状在我院自愿进行纤维支气管镜及BALF检查,经体检及X线检查证实为健康者13名,作为BALF对照组。结果IPF患者BALF及血清中MMP9水平为(245±26)和(203±32)ng/L,对照组为(205±22)和(186±16)ng/L,两组相比差异无统计学意义;IPF组BALF及血清中TIMP1水平[(522±81)、(166±29)ng/L]高于对照组[(201±31)、(87±16)ng/L],差异有统计学意义;IPF组BALF及血清中MMP9/TIMP1比值(0.53±0.18,1.5±0.3)低于对照组(1.06±0.38,2.6±0.5)。HRCT、肺功能评分及BALF中上述指标与MMP9无明显相关性,与TIMP1呈正相关,与MMP9/TIMP1比值呈负相关。结论IPF患者肺纤维化的发生与TIMP1水平升高及MMP9/TIMP1比值降低对细胞外基质降解的抑制有关,后者可能意义更大;患者肺影像学及肺功能变化可能也与此有关。     

特发性肺纤维化患者死亡预后因素的回顾性队列研究

目的 探讨特发性肺纤维化(IPF)患者的临床、影像学和肺生理学指标与疾病预后的关系.方法 2000年1月至2004年6月在中国医科大学附属第一医院126例经临床诊断的IPF患者作为研究对象,其中男81例,女45例,年龄51～67岁,平均61岁.采用单因素和多因素Cox比例风险回归分析评估患者临床、呼吸生理、BALF及HRCT等参数的死亡风险度,采用Kaplan-Meier检验比较组间生存率.结果平均随访时间为29.6个月,IPF患者的生存率为46.8%(59/126),确诊后的中位生存期为30个月.采用糖皮质激素和(或)细胞毒类药物治疗与采用其他药物治疗的生存率比较,差异无统计学意义(Ward值为2.3,P>0.05);性别和吸烟状态的组间生存率比较,差异无统计学意义(Ward值为0.11和1.65,均P>0.05).将单因素Cox比例风险回归分析结果中有意义的变量中位数为截点值,进行组间生存率比较,结果表明,呼吸困难评分、FVC、肺总量、DLCO、BALF中性粒细胞、嗜酸粒细胞、胸部HRCT网格影和蜂窝肺的组间生存率差异均有统计学意义(Logrank值为13.52～57.52,均P<0.05).多因素Cox比例风险回归分析结果表明,肺总量、DLCO、HRCT网格影和蜂窝肺均为影响IPF患者预后的因素(Ward值为5.76～74.20,均P<0.01).结论 肺总量、DLCO、BALF细胞学指标和肺纤维化程度是影响IPF患者预后的主要因素,其中肺总量和DLCO与IPF患者的预后呈负相关.糖皮质激素和(或)细胞毒类药物不能改变IPF患者的预后.     

结节病患者肺功能与支气管肺泡灌洗液细胞学关系的研究

目的 探讨结节病患者不同影像分期之间肺功能指标、支气管肺泡灌洗液细胞学的改变以及两者的相关性.方法 回顾性调查71例结节病患者肺功能以及支气管肺泡灌洗液检查的资料.结果 在结节病患者不同影像分期之间肺功能指标用力肺活量(FVC)占预计值%、第1秒用力呼气容积(FEV1)占预计值%、肺总量(TLC)占预计值%以及肺一氧化...     

A novel seven-gene risk profile in BALF to identify high-risk patients with idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal heterogeneous disease with a varied clinical course that is difficult to predict. Accurate predictive models are urgently needed to identify individuals with poor survival for the optimal timing of referral for transplantation and provide some clues for mechanistic research on disease progression.MethodsWe obtained the gene expression profiles of bronchoalveolar lavage fluid (BALF) from the Gene Expression Omnibus. Individuals from the {"type":"entrez-geo","attrs":{"text":"GPL14550","term_id":"14550"}}GPL14550 platform were assigned to the derivation cohort (n=112) and individuals from the {"type":"entrez-geo","attrs":{"text":"GPL17077","term_id":"17077"}}GPL17077 platform to the validation cohort (n=64). Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were applied to select candidate genes for overall survival. A nomogram model was constructed based on Cox hazard regression analysis. The model was assessed by C-statistic, calibration curve, and decision curve analysis (DCA) and was externally validated.ResultsA nomogram model comprising seven genes was constructed. Excellent discrimination and calibration were observed in the derivation (C-index 0.815) and validation (C-index 0.812) cohorts. The AUCs for predicting 1-, 2- and 3-year survival were 0.857, 0.918, 0.930 in the derivation cohort and 0.850, 0.880, 0.925 in the validation cohort, respectively. DCA confirmed the clinical applicability of the model. A risk score based on the model was an independent prognostic predictor and could divide patients into high- and low-risk groups. The Kaplan-Meier analysis displayed that high-risk patients exhibited significantly poorer survival compared with low-risk patients. Gene Set Enrichment Analysis (GSEA) showed that high-risk patients were primarily enriched in inflammatory hallmarks, and single sample GSEA (ssGSEA) indicated that the high-risk group is closely correlated with the immune process. These lead to increased insight into mechanisms associated with IPF progression that inflammation mediated by immune response might be involved in the disease progression.ConclusionsThe novel BALF seven-gene model performed well in risk stratification and individualized survival prediction for patients with IPF, facilitating personalized management of IPF patients. It deepened the understanding of the role of inflammation in IPF progression, which needs to be further studied.     

IL-17和IL-6在特发性肺纤维化患者中的表达及意义

目的探讨特发性肺纤维化患者支气管肺泡灌洗液和血清中白细胞介素-17(IL-17)和白细胞介素-6(IL-6)水平的变化及临床意义。方法选择:31例特发性肺纤维化患者(病例组)和14例健康就诊者(对照组)为研究对象,采用ELISA法检测两组组BALF和外周血中IL-17和IL-6的水平,分析病例组患者IL-17和IL-6水平与其肺功能的关系。结果 IPF组患者血清和BALF中IL-6水平为均明显高于对照组水平(P0.01);IPF组患者血清和BALF中IL-17水平均明显高于对照组水平(P0.01);IPF组患者血清和BALF患者的IL-6和IL-17水平与FVC、FEV1、FEV1∕FVC和DLco水平均呈现明显的负相关性(P均0.01)。结论 IL-17和IL-6可能在IPF的发病过程中发挥一定作用,并有可能作为判断IPF病情严重程度的一项指标。     

Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases

We analyzed phospholipids of human bronchoalveolar lavage (BAL) fluids from patients with interstitial lung diseases; idiopathic pulmonary fibrosis (IPF), sarcoidosis, and eosinophilic granuloma (EG) and compared them to those of normal subjects. The content of phospholipid/ml of BAL fluid was significantly decreased in IPF. There was a significant decrease in phosphatidylglycerol (PG) and an increase in phosphatidylinositol (PI) in IPF but not in sarcoidosis and EG. Thus, the PG to PI ratio was significantly decreased in IPF. The dipalmitoyl species of phosphatidylcholine (PC) was found to be significantly decreased in IPF and sarcoidosis by molecular species analysis using high performance liquid chromatography. In contrast, the unsaturated species were increased in these diseases. The decrease in dipalmitoyl PC appeared to be a common feature in interstitial lung diseases. The changes in phospholipids in BAL fluids, especially decreases in DPPC and PG to PI ratio in IPF, appear to indicate that damage of alveolar Type II cells and/or of metabolic disturbance in pulmonary surfactant occurs in IPF.     

特发性肺纤维化和结节病患者基质金属蛋白酶的变化及其临床意义

目的 探讨特发性肺纤维化(IPF)和结节病患者基质金属蛋白酶(MMP)-1和MMP-7的变化及其临床意义. 方法 经临床确诊的IPF患者44例为IPF组,其中男23例、女21例,年龄46～70岁,平均(58±9)岁;Ⅱ期结节病患者20例为结节病组,其中男9例、女11例,年龄35～65岁,平均(50±12)岁.均进行肺功能和支气管肺泡灌洗检查.采用酶联免疫吸附试验测定血清和BALF中MMP-1和MMP-7水平.非正态分布的计量资料以中位数表示,采用两个独立样本比较的Wilcoxon秩和检验进行统计学分析,采用Spearson相关性检验进行相关分析. 结果 IPF组患者血清和BALF中MMP-1中位数(范围)分别为3.78(0.14～13.44)和1.09(0.04～5.14)μg/L,均明显低于结节病组的7.79(4.67μ10.68)和2.08(0.05μ4.16) μg/L,两组血清中MMP-1水平的差异有统计学意义(z=-3.53,P<0.01);IPF组患者血清和BALF中MMP-7中位数(范围)分别为7.83(3.57～14.37)和3.75(1.10～9.87)μg/L,均明显高于结节病组的4.04(0.06～9.94)和1.16(0.02～4.47)μg/L,两组血清和BALF中MMP-7水平的差异均有统计学意义(z值分别为-3.84和-5.33,均P<0.01).IPF组患者血清中MMP-7水平与DLCO占预计值%和BALF中性粒细胞构成比呈显著负相关(r值分别为-0.56和-0.47,均P<0.01),IPF组患者BALF中MMP-7水平与DLCO占预计值%呈显著负相关(r=-0.31,P<0.05). 结论 在肺纤维化炎症细胞浸润阶段MMP-1水平高于纤维化阶段,在纤维化基质重塑阶段MMP-7水平高于炎症阶段.MMP-7有可能作为肺纤维化严重程度的参考指标.     

Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema

Background and objective: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper lobe emphysema together with lower lobe fibrosis. The aim of this study was to examine whether cytokine levels in the alveolar space are associated with emphysematous changes superimposed on pulmonary fibrosis. Methods: Consecutive patients (n = 102), diagnosed with pulmonary fibrosis were retrospectively evaluated. Cytokine levels and differential cell counts in bronchoalveolar lavage (BAL) fluid, pulmonary function, computed tomography (CT) scores and levels of serum markers were compared between patients with or without emphysema. Results: Among the 102 patients (14 females, mean age 68 years), 38 (37%) had evidence of upper lobe emphysema on computed tomography (CT). Levels of epithelial neutrophil activating peptide 78 (ENA‐78/CXCL5) and interleukin (IL)‐8/CXCL8 in BAL fluid were significantly higher in patients with emphysema. Vital capacity (VC, % predicted) was greater, and ratio of forced expiratory volume in 1 s/forced vital capacity and diffusing capacity of carbon monoxide (DL_CO)/alveolar volume (V_A) were lower in patients with emphysema. CXCL8 and CXCL5 levels were associated with percentage or absolute numbers of neutrophils in BAL fluid. In addition, CXCL8 levels were inversely correlated with VC and DL_CO/V_A, and positively correlated with composite physiological index (CPI) and the extent of areas of low attenuation on CT. Conclusions: Increased CXC chemokine levels in the airspaces may be associated with emphysematous lung changes in patients with pulmonary fibrosis.