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.     

特发性肺纤维化患者生存预后因素的回顾性分析

目的 探讨临床指标、肺生理变化及BALF细胞分类对判断特发性肺纤维化(IPF)患者预后的价值,评估糖皮质激素或糖皮质激素联合细胞毒类药物治疗IPF患者的影响.方法 65例IPF患者分别接受临床评估和血气分析、肺功能、胸部高分辨率CT、心脏超声及BALF检查,分析各项指标对判断IPF患者预后的意义.采用Cox比例风险回归评价各指标的死亡危险度,采用Kaplan-Meier检验进行组间生存率比较.结果 在平均随访38个月内,IPF患者的总体生存率为43.1%,确诊后的中位生存期为39个月;体重指数、杵状指、ESR、氧合指数、SaO2、肺总量占预计值%、DLCO占预计值%、肺动脉压和BALF中的中性粒细胞百分率是IPF患者预后的影响因素,其死亡危险度为0.842～1.945,Wald值为3.782～12.963,均P＜0.05;体重指数、杵状指、ESR、氧合指数、肺总量占预计值%和DLCO占预计值%的组间生存率比较,差异均有统计学意义(Log-rank值为3.907～10.452,均P＜0.05);采用糖皮质激素治疗和糖皮质激素联合细胞毒类药物治疗的IPF患者与未采用上述药物治疗的IPF患者组间生存率比较,差异无统计学意义(Log-rank值为2.405,P＞0.05).结论 体重指数、杵状指、ESR、氧合指数、肺总量占预计值%和DLCO占预计值%对IPF患者的生存预后可能具有参考价值,糖皮质激素或糖皮质激素联合细胞毒类药物治疗不能改变IPF患者的预后.

Abstract：

Objective To investigate the prognostic implications of clinical and physiological variables, and the cellular classification of bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF). The effect of treatment with glucocorticoids with or without cytotoxic drugs was also evaluated. Methods The significances of clinical, arterial blood gas analysis, pulmonary function test, lung high-resolution computed tomography, echocardiography and BALF in the prognosis of patients with IPF were assessed in 65 patients with IPF at diagnosis. Univariate Cox proportional-hazards regression analysis was used to evaluate the various parameters associated with hazard ratio. The survival rates of all groups were compared using the Kap]an-Meier method. Results In 38 months of average follow-up time,the survival rate of the patients was 43. 1%, and the median survival time was 39 months after diagnosis.Univariate Cox proportional-hazards regression analysis showed that body mass index, clubbing fingers,ESR, PaO2/FiO2, SaO2, TLC%, DLCO%, pulmonary arterial pressure and the percent of neutrophil in BALF were factors that affected the prognosis of the patients with IPF ( HR 0. 842 - 1. 945, Wald 3. 782 -12. 963, P ＜0. 05). In the meanwhile, the patients were divided into 2 groups by the median of significant variables in univariate Cox proportional-hazards regression analysis (the cut off point value ), and the survival rate group comparison showed statistically significant difference in body mass index, clubbing fingers, ESR, TLC% as well as DLCO% ( Log-rank 3.907 - 10. 452, P ＜ 0. 05 ), while glucocorticoids with or without cytotoxic drugs for patients with IPF did not change the prognosis ( Log-rank 2. 405, P ＞0. 05). Conclusions Body mass index, clubbing fingers, ESR, PaO2/FiO2, TLC%, and DLCO% maybe the factors affecting the prognosis of patients with IPF, while glucocorticoids with or without cytotoxic drugs did not change the course of IPF.     

血清LTBP2作为特发性肺纤维化患者预后标志物的研究

目的探讨血清潜在转化生长因子结合蛋白2(LTBP2)作为特发性肺纤维化(IPF)患者预后标志物的临床价值。 方法回顾性选择2010年1月至2015年12月来我院接受治疗的IPF患者120例。根据患者随访结局分为预后良好组70例和预后不良组50例。比较两组患者在临床特征方面的差异。血清LTBP2水平与临床特征间相关性利用Pearson相关分析。影响IPF患者预后的多因素分析采用Cox比例风险模型。采用受试者工作特征曲线(ROC)筛选切点，计算曲线下面积评估血清LTBP2的预测效力。 结果预后不良组在SGRQ评分、血清LTBP2水平方面高于预后良好组，差异有统计学意义(P<0.05)，在6 min步行试验、肺总量(TLC)占预计值百分比、肺弥散量(DLco)占预计值百分比、LAA-950、平均肺密度比、PaO₂方面低于预后良好组，差异有统计学意义(P<0.05)。Pearson相关分析结果显示，血清LTBP2水平与TLC占预计值百分比、DLco占预计值百分比、LAA-950、平均肺密度比、PaO₂呈负相关(P<0.05)，与SGRQ评分呈正相关(P<0.05)。Cox比例风险模型分析结果显示，PaO₂、血清LTBP2水平是是影响IPF患者预后的危险性因素(P<0.05)。血清LTBP2水平预测IPF患者预后不良的最佳诊断界值为12.25 ng/ml。 结论血清LTBP2水平偏高不利于IPF患者预后，血清LTBP2水平可作为预测IPF患者预后的重要分子标志物。     

特发性肺纤维化患者嗜酸粒细胞与肺功能相关性的研究

特发性肺纤维化(IPF)发病机制至今尚未完全清楚。大量研究结果表明,肺泡巨噬细胞、淋巴细胞和中性粒细胞等免疫细胞及其分泌的炎症介质在IPF的发病、进展方面起重要作用;临床上将IPF归为中性粒细胞型肺泡炎,强调了中性粒细胞在IPF中的作用。但是,近年来嗜酸粒细胞在间质性肺疾病(ILD)发病中所起的作用日益受到关注。一些研究发现嗜酸粒细胞的激活及其释放的嗜酸粒细胞阳离子蛋白(ECP)是引起肺间质纤维化的重要因素[1,2]。我们对32例IPF患者支气管肺泡灌洗液(BALF)中白细胞和肺通气功能、弥散功能[单次呼吸法一氧化碳弥散(DLCO)]…     

肺泡蛋白沉着症肺功能检查特点:附27例分析

目的 肺泡蛋白沉着症(PAP)在临床上极为罕见,其肺功能检查特点的报道也极少,本研究目的在于探讨肺功能检查在PAP诊断和治疗中的价值.方法 回顾性分析本院呼吸疾病研究所经肺组织病理(过碘酸雪夫反应阳性)确诊的27例PAP患者的临床资料.全部病例均给予肺通气和弥散功能测试,其中12例进行了肺容积测试.比较了10例行支气管肺泡灌洗(BAL)治疗的患者在灌洗前、后肺功能的改变情况.结果 27例患者入院后的基础通气肺功能情况:用力肺活量(FVC):(79.67±16.21)%;第1秒用力呼气容积(FEV1):(83.94±16.07)%,一秒率(FEV1/FVC):(89.20±5.50)%;最大呼气流量(PEF):(107.64±17.73)%;肺一氧化碳弥散量(DLCO):(49.27±21.83)%;DLCO与肺泡通气量比值(DLCO/VA):(69.92±20.11)%.肺总量(TLC):(80.60±19.56)%;残气容积(RV):(86.03±38.10)%;残总比(RV/TLC):(32.73±9.48)%;功能残气量(FRC):(84.91±28.08)%.27例患者基础肺功能下降的异常率:FVC:55.6%(15例);FEV1:44.4%(12例);FEV1/FVC:0%(0例);PEF:3.7 %(1例);DLCO:88.9%(24例);DLCO/VA:70.4%(19例).12例患者肺容积的异常率:TLC下降者占50%(6例);RV下降者占41.7%(5例),升高者占16.7%(2例);RV/TLC升高者占50%(6例);FRC下降者占33.3%(4例).10例进行BAL治疗的患者术后肺功能改善率:FVC:5.47%;FEV1:5.50%;DLCO:31.07%;DLCO/VA:20.35%.灌洗前后DLCO及DLCO/VA差异有统计学意义(t=-3.551,-3.159;P=0.006,0.012).结论 PAP的肺功能检查以肺限制性通气功能障碍及肺弥散功能障碍为常见,尤其为弥散功能障碍.PAP经BAL治疗后肺弥散功能有显著性改善.     

特发性肺间质纤维化合并肺气肿的临床特征分析

目的探讨特发性肺问质纤维化（IPF）合并肺气肿（CPFE）的临床特点及意义,提高对本疾病的认识和诊断水平。方法选择31例IPF合并CPFE的患者和36例单纯IPF患者作为研究对象,回顾性分析两组患者临床资料、肺功能、血气分析、胸部高分辨CT（HRCT）表现及生存时间差异。结果两组性别、年龄、吸烟者比例无显著差异,CPFE组吸烟指数为（38．1±9．0）年包,明显高于IPF组。CPFE组患者用力肺活量（FVC）占预计值％为（78．6±11．2）％、第1秒用力吸气容积FEV1／FVC为（69．1±6．0）％、一氧化碳弥散量（DLCO）占预计值％为（32．1±11．8）％,均明显低于IPF组,CPFE组患者肺总量（TLC）占预计值％为（76．3±8．1）％,VC占预计值％为（70．7±11．6）％,均明显高于IPF组。CPFE组患者肺动脉收缩压（CSPA）为（59．6±20．3）mmHg,明显高于IPF组。静息吸气状态下,CPFE组患者PaO2水平为（50．3±5．9）mmHg,明显低于IPF组。CPFE组患者胸部HRCT主要表现为双上肺野肺气肿和肺大疱,双下肺野呈网格影、蜂窝肺和牵张性支气管扩张。两组中位生存时间无统计学差异[分别为（38±5）和（41±4）个月,Х^2=0．55,P=0．63]。结论吸烟为CPFE的重要危险因素,当CPFE时,肺功能、血气分析、HRCT表现存在与单纯IPF不同的特点,与单纯IPF比较,预后无明显差异。     

骨密度测定对特发性肺纤维化预后的预测价值

目的探讨骨密度(BMD)与特发性肺纤维化(IPF)患者肺功能指标的关系,以及BMD对IPF预后的预测价值。方法选择2012年1月至2015年6月在本院诊治的89例IPF患者纳入研究。收集所有入组患者的一般资料,肺功能指标和随访结果;按随访结果分为预后良好组和预后不良组,比较两组各项指标的差异;采用Pearson相关法分析BMD与肺功能指标的相关性;采用Logistic多因素回归分析法评价各项临床指标对IPF患者预后的影响;绘制ROC曲线分析BMD对IPF患者预后的预测价值。结果2年随访期内89例IPF患者中失访5例,预后良好48例,预后不良36例,预后不良率为40.5%。预后不良组BMD水平显著低于预后良好组[(475.8±98.6)mg/cm^2 vs(598.4±97.7)mg/cm^2,t=5.668,P<0.001]。预后不良组合并骨质疏松症比例显著高于预后良好组(χ^2=4.227,P=0.040)。Pearson相关分析结果显示IPF患者BMD水平与肺弥散功能指标一氧化碳弥散量占预计值百分比(DLCO%)均呈显著正相关关系(r=0.391,P<0.001),与肺通气功能指标1s用力呼气容积(FEV 1)无相关关系(r=0.065,P=0.555)。Logistic多因素回归分析结果显示:IPF患者BDM和DLCO%均是预后不良的影响因素(OR=1.012,95%CI 1.004~1.021,P=0.005;OR=1.322,95%CI 1.161~1.506,P<0.001)。ROC曲线分析显示:BMD和DLCO%预测IPF患者预后不良的ROC曲线AUC分别是0.810(0.719,0.900)和0.893(0.816,0.970),经Z检验两者差异无统计学意义(Z=1.376,P=0.169)。BMD预测IPF患者预后不良的cut-off值为560.1mg/cm 2,对应的灵敏度和特异度分别为68.8%和86.1%。结论IPF预后不良患者BMD水平显著降低,BMD可能成为早期预测IPF预后的新指标。     

特发性肺纤维化患者辅助性T细胞1/辅助性T细胞2的研究

目的 对特发性肺纤维化(IPF)患者辅助性T细胞1(Th1)/辅助性T细胞2(Th2)进行研究,探讨Th1/Th2能否反映疾病的严重性,能否预测疾病的进展.方法 入选83例IPF患者,应用酶联免疫吸附测定法检测所有受试者血清、支气管肺泡灌洗液(BALF)中γ干扰素(IFNγ)、白细胞介素-4(IL-4)水平,并进行相关性分析.结果 (1)基线资料:IPF患者血清、BALF中IFNγ/IL-4比值(0.8±0.3;0.8±0.3)较对照组(1.4±0.2;1.4±0.2)显著降低;血清、BALF中IFNγ/IL-4比值与病程、呼吸困难评分、第1秒用力呼气容积(FEV1)占预计值百分比、用力肺活量(FVC)占预计值百分比、肺总量(TLC)占预计值百分比、最大去氧饱和度、6分钟步行距离(6MWD)、CT间质纤维化评分显著相关(血清:r值分别为-0.426、-0.623、0.487、0.455、0.517、-0.491、0.263、-0.569,P值均＜0.05;BALF:r值分别为-0.434、-0.637、0.480、0.456、0.501、-0.507、0.253、-0.605,P值均＜0.05);血清中IFNγ/IL-4比值与CT磨玻璃影评分呈正相关(r=0.340,P＜0.01).(2)随访:IPF患者血清中IFNγ、IL-4、IFNγ/IL-4在糖皮质激素治疗者与非糖皮质激素治疗者间差异无统计学意义.随访6个月后的呼吸困难评分、FEV1占预计值百分比、TLC占预计值百分比、CT磨玻璃影评分、CT间质纤维化评分、IFNγ和IL-4较基线值显著恶化.血清中IFNγ/IL-4比值变化与呼吸困难评分、FVC占预计值百分比、TLC占预计值百分比、肺一氧化碳弥散量占预计值百分比、6MWD、CT间质纤维化评分的变化显著相关(r值分别为-0.297、0.462、0.315、0.353、0.420、-0.307,P值均＜0.05).结论 IPF患者血清和BALF中Th1/Th2存在失衡,Th1/Th2可能反映IPF的严重性,随访时血清中Th1/Th2的变化可能会预测IPF的疾病进展.     

糖尿病前期及糖尿病与特发性肺纤维化患者肺功能的关系研究

目的探讨糖尿病前期及糖尿病与特发性肺纤维化(IPF)患者肺功能的关系。方法查阅徐州市中医院2016年1月—2018年7月住院病历资料并选取70例IPF患者作为IPF组,其中无糖尿病43例,糖尿病前期7例,糖尿病20例;按照年龄、性别1:1匹配原则选取2018年4—7月徐州市中医院体检中心健康体检者70例作为对照组。比较两组受试者肺通气功能指标[包括第1秒用力呼气容积占预计值百分比(FEV_1%pred)、用力肺活量占预计值百分比(FVC%pred)]、肺弥散功能指标[包括一氧化碳弥散量占预计值百分比(DLCO%pred)、脉搏氧饱和度(SpO_2)]、糖尿病前期或糖尿病者所占比例,并比较有无糖尿病IPF患者肺通气功能指标、肺弥散功能指标及糖皮质激素使用率。结果 (1)IPF组患者FEV_1%pred、FVC%pred、DLCO%pred及SpO_2低于对照组,糖尿病前期或糖尿病者所占比例高于对照组(P0.05)。(2)无糖尿病、糖尿病前期及糖尿病者FEV_1%pred、FVC%pred及糖皮质激素使用率比较,差异无统计学意义(P0.05);糖尿病前期及糖尿病者DLCO%pred及SpO_2低于无糖尿病者(P0.05);糖尿病前期与糖尿病者DLCO%pred及SpO_2比较,差异无统计学意义(P0.05)。(3)Spearman秩相关分析结果显示,血糖与IPF患者DLCO%pred(r_s=-0.509)、SpO_2(r_s=-0.287)呈负相关(P0.05)。结论 IPF并糖尿病前期或糖尿病患者肺弥散功能下降,且血糖与IPF患者肺弥散功能有关。     

特发性肺纤维化患者肺功能与CT表现相关性分析

目的探讨特发性肺纤维化(IPF)患者肺功能与计算机断层扫描(CT)表现的相关性。方法选择2011年12月至2015年12月在我院确诊的IPF患者32例为研究对象,对所有患者行肺功能检测和临床CT检查,观察其CT表现和解剖分布,评价肺功能与CT表现的相关性。结果本组32例IPF患者均存在不同程度肺功能损害,以网织影CT表现最多,占81.25%。FEV1/FVC与磨玻璃影呈负相关;TLC、FEV1、FVC、DLCO、DLCO/VA、Pa O2与网织影呈负相关,P(A-a)O2与网织影呈正相关;TLC、FEV1、FVC、DLCO、DLCO/VA与蜂窝肺呈负相关。结论 IPF患者的肺功能与CT表现存在强相关性,联合检测能比较准确地对IPF患者的病情进展、疗效及预后进行预测。     

间质性肺疾病支气管肺泡灌洗液中性粒细胞趋化因子和肿瘤坏 …

OBJECTIVE: To investigate the relationship between the level of the neutrophil chemotactic factor(NCF), tumor necrosis factor-alpha(TNF-alpha) in patients with interstitial lung disease(ILD) and the activity of ILD. METHOD: The NCF activities in the BALF and in the serum from 11 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects were determined using the membrane filter and radio-immunoassay. The level of TNF-alpha was also detected. RESULT: In the 7 IPF patients, the level of NCF and TNF-alpha (203 +/- 44 cells/10 HP, 11.7 +/- 2.9 ng/L) in the BALF was higher than that in 8 control patients (83 +/- 45 cells/10 HP, 6.5 +/- 1.4 ng/L, P < 0.01). The level of NCF and TNF-alpha in the BALF from 11 patients with sarcoidosis (186 +/- 50 cells/10 HP, 12 +/- 3 ng/L) was highet than those in 8 control patients (P < 0.01). The level of NCF and TNF-alpha in the BALF from patients with IPF was positive correlated with the percentage of neutrophil (NCF: r = 0.89, P < 0.01; TNF-alpha: r = 0.86, P < 0.05). The level of NCF and TNF-alpha in the BALF of patients with sarcoidosis was positive correlated with the percentage of lymphocyte (NCF: r = 0.78, P < 0.01; TNF-alpha: r = 0.73, P < 0.01. CONCLUSION: The level of NCF and TNF-alpha in the BALF from patients with IPF and sarcoidosis can act as the marker of the activity of alveolitis of IPF and sarcoidosis.     

间质性肺疾病患者血清和支气管肺泡灌洗液中内皮素1活？…

评价内皮素对肺纤维化发生，发展作用的影响。方法利用同位素放射免疫直接测定法，检测１０例肺结节病和８例特发性肺纤维化患外周血和支气管肺泡灌洗液中内皮素１（ＥＴ－１）的活性，并与８名健康非吸烟进行对照。结论ＥＴ－１在肺结节病和ＩＰＦ发病机制中起着重要作用，并可作为疾病活动性判定的一项重要参考指标。     

肺结节病支气管肺泡灌洗液中肿瘤坏死因子和中性粒细胞趋化 …

OBJECTIVE: To evaluate the role of cytokines released by the inflammatory cells and immunocytes from patients in pathogenesis of developing sarcoidosis. METHODS: With well- microchemotaxis and allergy immunology, the level of tumor necrosis factor-alpha (TNF-alpha) and neutrophil chemotactic factor (NCF) was measured in the serum and BALF of 11 sarcoidosis and 7 IPF and 8 normal subjects (non-smokers). RESULTS: The levels of TNFalpha (11.9 +/- 3.2, 11.7 +/- 3.0 ng x L(-1)) and NCF (191 +/- 51, 203 +/- 44 cell x 10HP(-1)) of BALF in the patients with sarcoidosis and IPF were significantly higher than these in control group (P < 0.01) and were higher than those in serum. The level of TNF-alpha in the BALF of patients with sarcoidosis was positively correlated with the percentage of lymphocytes (r = 0.73, P < 0.01). The activity of NCF in the BALF of patients with IPF was positively correlated with the percentage of neutrophils (r = 0.89, P < 0.01). CONCLUSIONS: It indicated that TNF-alpha and NCF might play an important role in the pathogenetic process of the sarcoidosis and IPF, and can act as the marker of activity of these diseases.     

特发性肺纤维化患者支气管肺泡灌洗液中白细胞介素13的水平及意义

目的　探讨特发性肺纤维化 (IPF)患者支气管肺泡灌洗液 (BALF)和外周血中白细胞介素 13 (IL 13 )水平的变化及其意义。方法　选择 17例IPF患者 (IPF组 )和 8名无器质性肺疾病者 (对照组 )。采用IL 13特异的酶联免疫吸附法测定 (ELISA)法检测 2组BALF和外周血中IL 13的水平 ,分析患者IL 13水平与其肺功能、血气之间的关系。结果　IPF组BALF和外周血中IL 13水平分别为(3 0 1± 86)ng/L、(178± 3 6)ng/L ;对照组分别为 (10 3± 2 4)ng/L、(55± 15)ng/L ,两者比较差异均有显著性 (P <0 0 1)。IPF组BALF中IL 13水平与BALF中性粒细胞数呈正相关 (r =0 786,P <0 0 1) ,与用力肺活量、一秒钟用力呼气容积、肺一氧化碳弥散量及动脉血氧分压均呈一定的等级负相关 (r分别为 -0 898、-0 878、-0 874、-0 890 ,P均 <0 0 1)。结论　IL 13可能在IPF的发病过程中起一定作用 ,并有可能作为判断病变进展情况的一项指标     

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...     

Prognostic value of clinical exercise testing in idiopathic pulmonary fibrosis

Current guidelines for referring patients with idiopathic pulmonary fibrosis (IPF) for lung transplantation, based on resting parameters, are insufficient to predict 3-year mortality. The aim of this study was to determine the prognostic value of cardio-pulmonary exercise testing (CPET) in patients with IPF. A multicentre retrospective study of 3-year outcome was made on 63 adult patients with IPF who underwent CPET with blood gas analysis. Demographic data, resting pulmonary function and CPET parameters were collected to perform a univariate survival analysis. To estimate prognosis at 3 years, a multivariate logistic regression analysis by Kaplan-Meier curves and log-rank tests was performed. Forty-four patients (70%) were alive without lung transplant at the end of the 3-year follow-up: 19 patients (30%) were dead (n=14) or transplanted (n=5). Univariate analysis indicated that: at rest lower TLC, FVC, DLCO and PaCO(2), higher alveolo-arterial gradient for oxygen [P(A-a)O(2)] and pH; at ventilatory threshold (VT) higher VE/VO(2) and VE/VCO(2) and at peak exercise higher VE/VO(2) and VE/VCO(2), higher pH and ΔP(A-a)O(2)/ΔVO(2) (mmHg/L), lower VO(2) peak, PaO(2) and VO(2)/FC were associated with a significantly lower survival at 3 years. The multivariate logistic regression analysis showed that CPT (<65%) and VE/VO(2) at VT (>45) were independently associated with a lower survival at 3 years. Restriction and hyperventilation at ventilatory threshold are major prognostic factors in the course of IPF. CPET with blood gas analysis may have a prognostic value in these patients and initial evaluation of these parameters can help to predict disease progression.     

BALF N-acetylglucosaminidase and beta-galactosidase activities in idiopathic pulmonary fibrosis

The lysosomal enzymes N-acetylglucosaminidase (N-ACGA) and beta-galactosidase (beta-gal) are involved in cellular collagen metabolism and may, therefore, be markers of fibrosis in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis (IPF). N-ACGA and beta-gal were analyzed in the bronchoalveolar lavage fluid (BALF) of patients with the histologic pattern of usual interstitial pneumonia (UIP, n=10) and controls (n=9). Cellular distribution in BALF as well as the concentration of TGF-beta a well-known mediator of fibroblast matrix deposition were correlated to the enzyme activities in both groups of patients. We found that both, N-ACGA (UIP: 25.2 nmol/l s +/- 3.4; controls: 73 nmol/l s +/- 1.3) and beta-gal (UIP: 4.7 nmol/l s +/- 0.5; controls: 2.4 nmol/l s +/- 0.3) were elevated significantly in BALF of patients with IPF compared to that of control patients (P<0.003). This increase was paralleled by an increase in neutrophils (IPF: 17.9% +/- 21.8; controls: 5.4% +/- 6.3; P=0.03) and eosinophils (IPF: 2.0% +/- 1.5; controls: 0.2% +/- 0.45; P=0.002) in BALF fluid. In addition, N-ACGA activity correlated closely with lung function (FVC, TLC, and DLCO), transforming growth factor-beta (TGF-beta) in BALF (r=0.77, P=0.008) and activated lymphocytes (r=0.66, P=0.0021). Our findings suggest that measurement of lysosomal enzymes such as N-ACGA may represent a useful indicator of fibrotic activity in IPF.