炔丙基甘氨酸增加高肺血流大鼠肺动脉结缔组织生长因子的表达

目的 探讨硫化氢(H2S)生成酶抑制剂炔丙基甘氨酸(PPG)对高肺血流大鼠肺动脉结缔组织生长因子(CTGF)表达的影响.方法 将32只雄性SD大鼠随机分为分流组、分流 炔丙基甘氨酸(PPG)组、假手术组和假手术 PPG组,每组8只.在大鼠高肺血流动物模型上,观察肺组织H2S含量、血浆ET-1含量、肺组织ET-1 mRNA的表达和肺动脉CTGF蛋白表达的变化.结果 分流4周后,肺组织H2S含量、血浆ET-1含量、肺组织ET-1 mRNA表达及肺动脉CTGF表达均明显升高(P<0.01);应用PPG干预后,分流 PPG组大鼠H2S含量明显降低;血浆ET-1含量、肺组织ET-1 mRNA的表达及肺动脉CTGF蛋白表达比分流组明显增加(P<0.05).结论 内源性H2S可能通过降低血管活性肽ET-1及CTGF在肺组织的表达参与对高肺血流时肺循环结构与功能的调节.     

门静脉高压症患者血浆内源性硫化氢含量的变化和意义

目的:观察血浆内源性硫化氢(H2S)在门静脉高压症不同Child级别患者中的差异及其在门静脉高压症发病中的可能作用。方法:测定2007年9月～2007年12月在我院住院治疗的门静脉高压症患者(23例)和同期体检健康人群(25例)的血浆H2S水平、肝功能、门静脉管径,分析血浆H2S含量差异与门静脉高压症的关系。结果:门静脉高压症患者血浆H2S水平较健康人低;Child不同级别H2S含量存在明显差异,血浆H2S含量与门静脉管径具有负线性相关关系。结论:内源性H2S可能参与门静脉高压症的病理过程。     

心血管组织钙化时内源性硫化氢系统下调

目的：观察心血管组织钙化时内源性硫化氢生成系统(CSE/H2S)的变化，以探讨内源性硫化氢在心血管组织钙化中的作用及血管钙化的细胞分子机制。方法：在维生素D3 (Vit D3)和尼古丁(nicotine)诱导大鼠血管钙化模型上，测定钙含量、［45Ca2+］沉积及碱性磷酸酶（ALP）活性判断心血管钙化程度,采用生化法测定血浆、心肌组织和主动脉H2S含量及CSE活性，半定量RT-PCR方法测定心血管组织CSE mRNA水平。结果：钙化组大鼠心肌组织钙含量较对照组高3.8倍,主动脉钙含量、［45Ca2+］ 沉积及ALP 活性分别较对照组高6.8倍、1.4倍和 1.9倍（P＜0.01）；钙化组大鼠血浆H2S含量较对照组低39%（P<0.01），心肌和主动脉组织的 H2S含量也分别较对照组低39%和31%，CSE mRNA表达也分别低28％和36％（P<0.01），CSE活性分别低56%和53%(P<0.01)。结论：钙化心血管组织CSE/H2S通路受抑制，内源性H2S生成减少。     

急性脑梗塞患者血浆TXB_2、6-Keto-PGF_(1α)含量的变化

本文报告了31例健康人血浆中TXB_2与6-Keto-PGF_(1α)的测定结果。并对51例急性脑梗塞患者血浆中TXB_2、6-Keto-PgF_(1α)进行了测定,结果表明急梗组病人较对照组血浆TXB_2明显增高P<0.01);而病入血浆中6-Keto-PGF_(1α)与对照组相比也有明显差异(P<0.01),TXB_2/6-Keto-PGF_(1α)比值增大。40—50岁患者,血浆TXB_2含量明显高于同龄对照组(P<0.01),而6-Keto-PGF_(1α)含量组间差异不明显。测定结果提示,TXB_2/6-Keto-PGF_(1α)失衡与脑血栓性梗塞发生有关;在急性脑梗塞发病机制中可能由于TXA_2生成增多,血小板活性增强所致。     

冠心病患者介入治疗后血浆新型气体信号分子硫化氢及一氧化氮变化的临床研究

目的研究新型气体信号分子硫化氢（H2S）及一氧化氮（NO）在冠心病患者和冠脉造影正常者血浆中含量的差异及介入治疗对其的影响,探讨其在冠心病发病及介入治疗中的病理生理意义。方法冠心病组40例,造影正常组17例,采用硫敏感法测定术前血浆H2S含量并用Greiss法测定血浆中NO含量,动态监测冠心病患者冠状动脉造影前后、介入治疗后即刻、术后24h和72h血浆H2S、NO含量,分析冠心病组和造影正常组患者血浆H2S、NO含量的差异及介入治疗后血浆H2S和NO的变化。结果冠心病患者血浆H2S、NO含量远低于造影正常组（P均〈0.01）;冠脉双支和多支病变组血浆H2S含量差异无统计学意义（P〉0.05）,但均明显低于单支病变组（P〈0.05和P〈0.01）。不同支数病变冠心病患者血浆NO含量差异无统计学意义。冠脉血管有闭塞组其血浆H2S、NO含量明显低于单纯狭窄组（P均〈0.05）;支架植入术后复查狭窄者NO含量明显低于无狭窄者（P〈0.05）,H2S含量也低于无狭窄者,但差异无统计学意义（P〉0.05）。冠状动脉造影术对血浆H2S、NO含量无影响,但PCI治疗术后即刻H2S、NO含量显著降低;H2S含量术后24h恢复至术前水平,NO含量术后24h降至最低水平,72h仍未恢复至术前水平。结论 H2S和NO可能参与了冠心病的发病过程及介入治疗后急性血管闭塞及再狭窄的发生,血浆H2S含量的高低与冠脉血管病变严重程度相关。     

硫化氢供体对阿霉素心肌病大鼠心肌结构及心功能的影响

目的探讨给予外源性硫化氢(H2S)供体硫氢化钠(NaHS)对阿霉素(ADR)心肌病大鼠心功能及心肌结构的影响及其作用机制。方法雄性Wistar大鼠54只,随机分5组(1)ADR组;(2)ADR 小剂量NaHS组;(3)ADR 大剂量NaHS组;(4)对照组;(5)NaHS组。药物均腹腔注射,连续用药10周,检测心功能和血流动力学指标,于光镜及电镜下观察显微及超微结构,并测定其血浆及心肌组织中H2S含量。结果阿霉素组大鼠心功能较对照组明显降低(P<0.01),心肌组织呈心肌病样改变,且血浆及心肌组织中H2S含量均明显低于对照组(P<0.001)。经补充外源性H2S供体NaHS后,大鼠心功能较前明显改善,心肌组织病理损害程度明显减轻。结论H2S参与了大鼠阿霉素心肌病的发病过程,补充外源性H2S可以改善阿霉素心肌病大鼠心功能,减轻心肌损伤。     

CO上调大鼠胸主动脉中硫化氢/胱硫醚-γ-裂解酶体系

目的研究一氧化碳(CO)对正常大鼠主动脉中硫化氢(H2S)/胱硫醚-γ-裂解酶(CSE)体系的影响。方法取W istar大鼠胸主动脉分为对照组、血红素组(终浓度10-4mol/L)和锌原卟啉组(终浓度10-5mol/L),每组各9例,用硫电极法测定孵育液中H2S含量和组织中H2S生成率。结果与对照组相比,血红素组孵育液中H2S含量明显升高(P<0.01),而锌原卟啉组H2S含量明显降低(P<0.05)。与对照组相比,血红素组胸主动脉组织中H2S生成率明显升高(P<0.01),锌原卟啉组H2S生成率明显降低(P<0.05)。结论在正常大鼠胸主动脉组织孵育中CO上调H2S/CSE体系。     

急性脑出血患者血浆皮质醇含量变化的临床意义

目的:探讨皮质醇在急性脑出血疾病中的变化。方法:采用放射免疫分析,对68例急性脑出血患者和40例正常人的血浆中皮质醇含量进行测定。结果:患者血浆中皮质醇含量较对照组明显增高(P<0.001)。皮质醇昼夜分泌规律出现明显紊乱,且上述变化与病情的严重程度呈正相关。随着病情改善,血浆皮质醇亦逐渐恢复。结论:急性脑出血患者血浆皮质醇的含量与疾病的严重程度和预后有着密切的关系。     

L-精氨酸对大鼠高肺血流所致肺血管结构重建及内源性硫化氢的影响

探讨L 精氨酸 (L Arg)对高肺血流量所致大鼠肺血管结构重建和内源性硫化氢的影响及其机制。 2 1只SD大鼠随机分为对照组 (n =7) ,分流组 (n =7) ,分流 +L 精氨酸组 (n =7)。对后两组大鼠行腹主动脉、下腔静脉分流术。对分流 +L 精氨酸组大鼠每天灌胃L Arg 1g kg。 1 1周后观察肺动脉平均压 (mPAP)和右心室肥厚的改变。并且在光学显微镜和电子显微镜下观测肺血管结构的变化。测定血浆硫化氢含量和肺组织硫化氢产出率。结果表明 ,分流组大鼠mPAP、右心室 /体重 (RV BW)及右心室 /左心室 +室间隔 [RV (LV +S) ]比值明显高于对照组 (P <0 0 1 ) ,光镜下肺小血管肌化程度明显增强 ,电镜下 ,肺中、小肌型动脉内皮细胞增生、肥厚 ,平滑肌细胞由收缩表型向合成表型转化。分流组大鼠的血浆H2 S含量及肺组织CSE活性 (肺组织H2 S产出率 )明显低于对照组 (P <0 0 1 ) ,肺动脉平均压与血浆H2 S浓度呈负相关。同时L Arg缓解了肺动脉结构重建的形成 ,同时提高了内源性硫化氢水平 ,这可能是L Arg缓解高肺血流量所致肺动脉高压形成的机制之一。     

内毒素性急性肺损伤大鼠内源性H2S/CSE体系的变化

目的：观察内毒素性急性肺损伤（ALI）大鼠内源性硫化氢/胱硫醚-γ-裂解酶（H2S/CSE）体系、IL-1β和IL-10的动态变化。方法:健康雄性SD大鼠共80只，随机分为Ⅰ（对照）组；Ⅱ（LPS 1 h）组；Ⅲ（LPS 3 h）组；Ⅳ（LPS 6 h）组；Ⅴ（LPS 9 h）组；Ⅵ（LPS 12 h）组。给予LPS复制内毒素性ALI大鼠模型，分别于1、3、6、9、12 h处死，观察光镜和电镜下肺组织形态学改变，检测肺系数、肺湿/干重比、血浆中H2S含量、肺组织CSE活性、血清中IL-1β和IL-10的动态变化。结果:⑴LPS 1 h组，光镜和电镜下肺组织形态学无明显改变，肺系数、肺湿/干重比、血浆中H2S的含量和肺组织CSE活性与对照组比较无明显变化，血清中IL-1β和IL-10含量明显高于对照组(IL-1β，P<0.05；IL-10，P<0.01)。⑵LPS 3、6、9、12 h组，光镜和电镜下肺组织明显受损，超微结构明显改变，肺系数和肺湿/干重比明显高于对照组(P<0.05或P<0.01)，血浆中H2S的含量和肺组织CSE活性明显低于对照组（P<0.05 或P<0.01) ，血清中IL- 1β和IL-10的含量明显高于对照组(P<0.01)。结论:内源性H2S/CSE体系、IL-β和IL-10参与内毒素性ALI的病理生理过程。     

Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis

Cha S‐I, Chang C S, Kim E K, Lee J W, Matthay M A, Golden J A, Elicker B M, Jones K, Collard H R & Wolters P J (2012) Histopathology  61, 98–106 Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis Aims: The relationship of mast cells to the pathogenesis of lung fibrosis remains undefined despite recognition of their presence in the lungs of patients with pulmonary fibrosis. This study was performed to characterize the relationship of mast cells to fibrotic lung diseases. Methods and results: Lung tissues from patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), systemic sclerosis (SSc)‐related interstitial lung disease (ILD) and normal individuals were subjected to chymase immunostaining and the mast cell density quantified. Eosinophils were quantified by immunostaining for eosinophil peroxidase. Changes in lung function were correlated with mast cell density. Lung tissue obtained from IPF patients had a higher density of chymase‐immunoreactive mast cells than that from patients with HP, SSc‐related ILD or normal lungs. IPF lung tissue had a higher density of eosinophils than normal lung. There was no correlation between mast cell density and eosinophil density in IPF lung. IPF patients with high mast cell density had a slower rate of decline in forced vital capacity (FVC) than IPF patients with low mast cell density. Conclusions: Mast cell density in IPF lungs is higher than in other fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may predict slower disease progression.     

Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is a major interstitial lung disease (ILD). Recently, we established a new mouse model for ILD in which daily administration of interleukin (IL)-18 with IL-2 induces lethal lung injury, suggesting that IL-18 is involved in the pathogenesis of ILD. Here, utilizing immunohistochemistry, we have analyzed IL-18 and IL-18 receptor (IL-18R) alpha expression in the lungs of 18 patients with IPF/UIP and 13 control subjects by using monoclonal anti-IL-18 antibodies and a new monoclonal antibody for IL-18Ralpha (H44). IL-18 was expressed in bronchoalveolar epithelium, alveolar macrophages, and the endothelium of small vessels in control subjects, and was abundantly expressed in the majority of pulmonary cells in patients with IPF. IL-18Ralpha was expressed in bronchoalveolar epithelium and alveolar macrophages in control subjects, and was strongly expressed in interstitial cells in patients with IPF, especially in the fibroblastic foci (FF). Interestingly, IL-18Ralpha expression was only weakly observed in areas showing established fibrosis. Semiquantitative analysis revealed that the histologic FF score was significantly correlated with the IL-18Ralpha expression level in FF lesions. Moreover, IL-18 levels in the serum and bronchoalveolar lavage fluid of patients with IPF were significantly higher than those in control subjects. Our findings suggest IL-18 and IL-18R are involved in the pathogenesis of IPF/UIP.     

Broncho-alveolar lavage cells are the most significant reservoir of human cytomegalovirus genome

The aim of the study is to estimate human cytomegalovirus DNA copy number in different compartments (BAL cells, blood leukocytes, serum) in patients with idiopathic pulmonary fibrosis (IPF). There were 16 patients (mean age 40.87 +/-10.97; 9 males, 7 females) with newly diagnosed and so far not treated IPF included in the study. The diagnosis of IPF was confirmed by typical HRCT findings and/or lung biopsy histopathological examination (result of the biopsy: "usual interstitial pneumonia"). There were also 16 adult volunteers (mean age 36.75 +/- 6.43; 12 males, 4 females) included in the study as a control group. Using the real-time quantitative polymerase chain reaction the HCMV DNA copy number was estimated. The prevalence of HCMV DNA positive subjects in the IPF group (75%) was higher, but did not differ significantly from the control group (69%). The HCMV DNA copy number in 1 million BAL cells was significantly higher comparing to blood leukocytes, both in IPF and control group (log10 = 2.7 vs. 1.2 for IPF and 2.8 vs. 0.9 for control, respectively). Higher mean HCMV DNA copy number was observed in IPF patients comparing to control group (log10 = 3.2 for IPF and 2.0 for control) in 1 mL of blood serum. We concluded that the lungs play an important role in human cytomegalovirus latency and infection reactivation and thus could be a cofactor modulating the course of IPF in humans. The contribution of HCMV infection in IPF patients should be taken into account during immunosuppression therapy planning.     

Idiopathic pulmonary fibrosis vs. pulmonary involvement of collagen vascular disease: HRCT findings.

The purpose of this study is to assess the differences of high-resolution CT (HRCT) findings in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary involvement of collagen vascular disease (CVD). We analyzed the HRCT findings of 33 patients with IPF and 23 patients with CVD in terms of predominant pattern, site of involvement, mediastinal lymph node enlargement, pleural change, and pulmonary volume loss. The predominant HRCT pattern was honeycombing for IPF (58%), and ground-glass opacity for CVD (57%). Predominantly subpleural involvement was seen in 90% of IPF and 83% of CVD patients. Mediastinal lymph node enlargement was seen in 61% of the patients with IPF and 13% with CVD (p = 0.0004). Pleural thickening was seen in 97% of the patients with IPF and 35% with CVD and the severity of pleural thickening is statistically significant (p = 0.00001). Pleural effusion was seen in 6% of the patients with IPF and 26% with CVD (p = 0.0351). The hilar height ratio was more than 1.5 in 52% of the patients with IPF and 30% with CVD (p = 0.2620). Although HRCT findings of IPF and pulmonary involvement of CVD are similar and overlap considerably, but patients with IPF showed a tendency to more progressed fibrosis than patients with CVD.     

Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease

ObjectiveTo determine the plasma level of Wingless-related integration site 7b (Wnt7b) protein in rheumatoid arthritis (RA) patients (with and without interstitial lung disease (ILD)) and in idiopathic pulmonary fibrosis (IPF) patients and its relationship with RA disease activity and/or severity of pulmonary fibrosis. To assess the validity of plasma Wnt7b for the detection of ILD among RA patients.MethodThis case-control study included 128 subjects (32 RA-ILD, 32 RA, 32 IPF, and 32 healthy controls). RA and RA-ILD Patients were evaluated for disease activity by DAS28 and disease activity grades were recorded according to DAS28 grades. Laboratory parameters as Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF), Anti-citrullinated peptide (Anti-CCP) were recorded. Plasma Wnt7b levels were measured by ELISA. Diagnosis of pulmonary fibrosis (for RA-ILD and IPF patients) was done by high resolution computed tomography (HRCT) and its severity was assessed mainly by pulmonary function test using forced vital capacity (FVC) grading.ResultsComparison of Wnt7b plasma levels showed a significant difference between the studied groups with the P-value < 0.018 (RA-ILD had the highest levels). Post hoc analysis revealed a significant difference in Wnt7b plasma levels between RA-ILD and IPF groups (P = 0.008). Also, RA-ILD and control groups had a significant difference (P = 0.039). However, there was a non-significant relationship between Wnt7b plasma levels and RA disease activity as well as the severity of pulmonary fibrosis. ROC curve analysis for the plasma Wnt7b levels revealed that a level  ≥285.1 pg/ml had a sensitivity of 87.5% and a specificity of 43.8% for the detection of ILD in RA patients with positive likelihood ratio of 1.56 and negative likelihood ratio of 0.29.ConclusionRA-ILD patients had significantly higher plasma Wnt7b levels than the controls and IPF patients. These data suggest that the Wnt7b secretion is augmented by the concomitant presence of RA with pulmonary fibrosis. In addition, plasma Wnt7b may be used as a highly sensitive test for the detection of immunologically induced fibrotic changes in lung tissue among RA patients.     

MRP14 is elevated in the bronchoalveolar lavage fluid of fibrosing interstitial lung diseases

Pulmonary fibrosis is defined by an overgrowth of fibroblasts and extracellular matrix deposition, and results in respiratory dysfunction that is often fatal. It is the end stage in many chronic inflammatory interstitial lung diseases (ILD) such as sarcoidosis and idiopathic pulmonary fibrosis (IPF). The myeloid‐related proteins (MRPs) belong to the S100 family of calcium‐binding proteins and are highly expressed by neutrophils, macrophages and epithelial cells during chronic inflammation. MRP14 stimulates fibroblast proliferation in vitro and is expressed in granulomas from sarcoidosis patients. We hypothesized that MRP14 may be a biomarker for fibrotic interstitial lung diseases. The objective of this study was to investigate whether levels of MRP14 in the bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis and IPF correlate with clinical parameters. We used an enzyme‐linked immunosorbent assay (ELISA) to measure MRP14 in BALF of 74 sarcoidosis patients, 54 IPF patients and 19 controls. Mean BALF levels of MRP14 were elevated significantly in IPF (P < 0·001) and sarcoidosis (P < 0·05) patients compared to controls. MRP14 levels were associated linearly with sarcoidosis disease severity based on chest radiographic stage. Moreover, BALF MRP14 levels were correlated inversely with diffusion capacity and forced vital capacity in sarcoidosis patients. In IPF patients, a correlation with BALF neutrophil percentage was found. In conclusion, BALF MRP14 levels are elevated in IPF and sarcoidosis and are associated with disease severity in sarcoidosis. The results support the need for further studies into the role of MRP14 in the pathogenesis of lung fibrosis.     

Association between MUC5B polymorphism and susceptibility and severity of idiopathic pulmonary fibrosis

Objectives: Idiopathic pulmonary fibrosis (IPF) is a group of lung diseases that cause irreversible architectural distortion and impair gas, and finally progressive pulmonary functional decline and death, in which the common variant in the promoter region of the mucin 5B (MUC5B) gene may be involved. The present study aims to investigate whether variants within the MUC5B gene rs35705950 contributed to IPF susceptibility and severity in Chinese Han Population. Methods: A total of 187 patients diagnosed with IPF and 250 healthy controls were enrolled in this study. All subjects were genotyped for MUV5B SNP rs35705950. The demographic, comorbidity, clinical and functional data were recorded. Results: The rs35705950 of MUC5B were found significantly associated with increased risk of IPF susceptibility. One way ANOVA analysis found that there was a significant decreased FVC (P < 0.0001) and DLco (P < 0.0001) in correction with the minor allele of the SNP rs35705950. In the 5 years’ follow-up, the carriers of the minor allele T increased mortality (P = 0.0294). Conclusion: This study demonstrated that the MUC5B polymorphism rs35705950 is associated with increased risk of idiopathic pulmonary fibrosis susceptibility, severity, and the decreased overall survival.     

硫化氢对肺动脉高压大鼠肺血管重塑及其抑制因子的影响

目的 探讨硫化氢（H2S）对肺动脉高压（PH）大鼠肺血管重塑及其抑制因子的影响。方法 30只雄性SD大鼠,通过随机数字表方式分为对照组10只、模型组10只及H2S干预组10只,其中模型组通过野百合碱诱导建立PH模型,H2S干预组在模型组基础上,对大鼠腹腔注射NaHS（56 μmol/kg）,对照组注射等剂量的生理盐水。制作模型4周后,测定各组大鼠血流动力学指标,计算右心室肥厚指数(RVHI),通过HE染色检测肺血管病理形态学变化,应用Western blotting及Real-time PCR检测丝裂原激活蛋白激酶（MAPK）家族中p38、c-Jun氨基末端激酶（JNK）蛋白的表达及表达含量。结果 各组血流动力学、RVHI、管壁厚度占血管直径百分比（WT%）、肺血管壁面积占血管截面积百分比（WA%）、p38 mRNA和JNK mRNA差异比较,具有统计学意义（P＜0.05）。其中模型组及H2S干预组平均体循环动脉压(MSAP)、平均肺动脉压(MPAP)、RVHI、WT%、WA%、p38mRNA和JNK mRNA表达水平均显著高于对照组（P＜0.05）,而H2S干预组MSAP、MPAP、RVHI、WT%、WA%、p38mRNA和JNK mRNA水平均显著低于模型组（P＜0.05）。肺动脉形态图显示,与对照组相比,模型组及H2S干预组的血管管壁厚度均增加,管腔变狭窄,但H2S干预组管厚度及管腔狭窄度均较模型组明显减轻;Western blotting显示,模型组及H2S干预组p38、JNK蛋白表达量均高于对照组,而H2S干预组p38、JNK蛋白表达量均低于模型组。结论 H2S可改善PH大鼠血流动力学、右心室肥厚指数;减轻肺动脉血管管壁增厚及管腔狭窄,抑制大鼠肺血管重构,其作用机制可能与H2S下调MAPK信号通路上JNK及p38蛋白的表达有关。     

The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis

Interstitial lung disease compatible with idiopathic pulmonary fibrosis (IPF) developed in 19 previously healthy patients. Although interstitial and/or honeycomb parenchymal fibrosis was present in all, there were patchy areas of paucicellular septal capillary injury along with corroborative direct immunofluorescent evidence of a humorally mediated microvascular injury syndrome. Significantly elevated factor VIII levels were seen in 17 of 18 patients tested. Antiphospholipids were present in all 18 patients tested, comprising antibodies of phosphatidylethanolamine, beta-2 glycoprotein, phosphatidylcholine, and/or phosphatidylserine. Anti-Ro and/or anti-ribonucleoprotein (RNP) antibodies were seen in 4 patients. Serologic evidence of infection with cytomegalovirus (CMV) was found in 9 patients and parvovirus B19 (B19) in 9 patients; 1 patient was not tested. Molecular studies revealed B19 DNA in 6 of 6 B19-seropositive patients. In situ hybridization studies revealed CMV RNA in pulmonary cells in patients with serologic evidence of active CMV infection despite the absence of cytopathic changes typical of CMV infection. Antiphospholipid antibodies, antiendothelial cell antibodies, and/or endotheliotropic viral infections related to B19 and CMV may be of pathogenetic importance to the evolution of IPF. This report underscores the potential importance of microvascular injury in the evolution of IPF.     

Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis

On the basis of earlier reports associating Epstein-Barr Virus (EBV) with half of the cases of idiopathic pulmonary fibrosis (IPF), we hypothesized that chronic infection with EBV or a closely related herpesvirus would be detected in all cases of IPF. We tested lung specimens from 33 IPF patients (8 patients with familial IPF and 25 patients with sporadic IPF) and 25 patients with other diseases as controls for the presence of eight herpesviruses using PCR-based techniques. One or more of four herpesviruses (cytomegalovirus [CMV], EBV, human herpesvirus 7 [HHV-7], and HHV-8) were detected in 32 of 33 (97%) subjects with IPF and in 9 of 25 (36%) controls (P < 0.0001). CMV, EBV, and HHV-8 were found more frequently in IPF patients than in controls (P < 0.05, P < 0.001, and P < 0.01 respectively). Two or more herpesviruses were detected in 19 of 33 (57%) IPF patients and in 2 of 25 (8%) controls (P < 0.001). Two or more herpesviruses and HHV-8 were found more frequently in patients with sporadic IPF than in patients with familial IPF (P < 0.05 for both comparisons), and CMV was found less frequently in patients with sporadic IPF than in patients with familial IPF (P < 0.05). Immunohistochemistry for EBV or HHV-8 antigen showed viral antigen primarily in airway epithelial cells. These data support the concept that a herpesvirus could be a source of chronic antigenic stimulation in IPF.