间质性肺病合并肺癌研究进展

间质性肺病和肺癌是呼吸内科常见疾病.近年来2种疾病的发病率都有明显升高的趋势,而且预后不良,特别是间质性肺病合并肺癌的出现,在其诊断和治疗方面都存在一定的难度和挑战.一方面,2种疾病的发病机制在一定程度上有共同之处;另一方面,肺癌的治疗会诱发间质性肺病的发生和急性加重.本文通过搜集近年来有关间质性肺病合并肺癌的流行病学、发病机制、临床特征、治疗和预后等相关问题的研究进展,并进行总结,以提高临床医师对间质性肺病合并肺癌的诊治水平.     

分子靶向药物心血管毒性的研究

分子靶向治疗在临床应用中取得非常鼓舞人心的效果，已经成为当前肿瘤治疗的新热点。然而，即使是针对性很强的癌细胞分子靶向治疗，也往往会导致心血管不良反应。随着越来越多的分子靶向药物的心血管不良反应逐渐被发现并受到重视，人们对其发生机制也有了初步的研究。本文将对分子靶向药物心血管毒性的研究做简要的综述。     

间质性肺病的治疗进展

间质性肺病是一组异源性肺部弥漫性疾病,其病因各异,故治疗方法及对药物的反应也各不相同。近年来,在对药物反应不佳的间质性肺疾病的治疗方面涌现了不少新的药物,本文将对各类间质性肺病的治疗以及近年来提出的可用于治疗间质性肺病的药物作一简要的概述。     

分子靶向药物相关性脂膜炎的研究进展

脂膜炎是一种累及皮下脂肪的非化脓性炎症性疾病，发病原因不明，临床表现多样且缺乏特异性。药物相关的皮疹部分可表现为脂膜炎，但由于对此类疾病的认识不足，目前关于药物相关性脂膜炎的报道不多。随着分子靶向药物在临床治疗中得到越来越广泛地应用，这类药物诱发的脂膜炎越来越多地被观察到。本文从脂膜炎的定义、分子靶向药物相关性脂膜炎的临床表现以及治疗等方面进行综述。     

肝癌靶向治疗导致肝损伤的应对策略

原发性肝细胞癌恶性程度高, 起病隐匿且发展迅速, 严重威胁人类的生命和健康。随着对肿瘤分子学特征研究的不断深入, 分子靶向药物已成为晚期肝癌患者的重要治疗手段。肝损伤是靶向药物常见的不良反应之一, 需引起重视。现主要从肝癌靶向药物导致肝损伤的发生情况、机制、危险因素、诊断和治疗等方面做简要阐述, 以期为肝癌患者临床安全应用靶向药物提供参考。     

分子靶向药物治疗肝细胞癌的研究进展

肝细胞癌(HCC)严重威胁着人类的生命健康。在临床治疗中,HCC治疗策略的选择越来越备受关注,随着对HCC发病机制的不断研究及分子生物学技术的飞速发展,分子靶向抗肿瘤药物治疗晚期HCC成为研究热点,并在临床实践中取得了显著疗效。回顾了近几年HCC分子靶向治疗药物最新临床应用研究进展及出现的相关问题,并针对其治疗策略的未来焦点进行展望,为应用研究和临床治疗HCC提供新的方向和参考。     

类风湿关节炎合并间质性肺病及血清表面活性蛋白研究进展

类风湿关节炎合并间质性肺病发病率、病死率高,早期易误诊、漏诊,尤其后期出现肺间质纤维化,临床治疗很困难.近年来,血清表面活性蛋白在间质性肺病研究较多.本文基于对类风湿关节炎合并间质性肺病的诊断和治疗进展方面的现代认识及血清表面活性蛋白在间质性肺病的研究进展进行综述,为该疾病早期诊断和治疗效果观察提供新的方法和手段.     

皮肤病相关间质性肺病13例临床分析

目的总结与皮肤病相关的间质性肺病的综合治疗效果。方法13例皮肤病相关间质性肺病患者，均给予抗炎、抗感染、氧疗等综合治疗。结果13例患者治疗后血气分析、肺功能及影像学明显改善。结论对于某些皮肤病相关的间质性肺病综合治疗效果较好，且早期治疗有助于改善预后。     

肺癌分子靶向治疗研究新进展

对肺癌分子发病机制和生物学行为的深入研究,促进了肺癌分子靶向治疗的发展。分子靶向治疗是指针对参与肿瘤发生、发展过程的细胞信号转导和其他生物学途径的治疗手段,具有高效和低不良反应的特点。本文主要对肺癌的分子靶向治疗研究进展进行概括总结。     

分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在肝细胞癌中的应用

肝细胞癌(HCC)是最常见的恶性肿瘤之一,发病隐匿,发展迅速,高复发的特点导致HCC患者长期生存面临巨大挑战。分子靶向药物与免疫抑制剂在HCC治疗中成为研究的热点,大量临床试验发现,联合治疗取得了不错的疗效。主要介绍了分子靶向药物与免疫抑制剂联合治疗及其他联合治疗在HCC中的应用,指出当前HCC治疗的最新研究热点在于系统治疗或局部治疗相关的联合治疗。     

多发性肌炎/皮肌炎合并肺间质病变的临床特征和预后

目的 研究多发性肌炎(PM)和皮肌炎(DM)合并肺间质病变(ILD)的临床特点和预后.方法 回顾性分析107例PM/DM患者的临床资料,包括首发症状、临床表现、实验室检查、影像学资料、治疗及预后.结果 107例PM/DM患者合并ILD有28例,ILD发生率为26.2%.①合并ILD的首发症状为关节炎或关节痛者高于无ILD(P<0.05);合并ILD临床表现为关节炎或关节痛、发热、干咳气促者明显高于无ILD(P<0.05).②DM合并ILD患者大多有特异性皮疹,呼吸困难较重(P<0.05),而PM合并ILD患者肌痛、肌无力较重(P<0.05).③合并ILD的红细胞沉降率(ESR)和C反应蛋白(CRP)明显高于无ILD(P<0.05);DM-ILD组肌酶谱以羟丁酸脱氢酶(HBDH)、天冬氨酸转氨酶(AST)升高为主(P≤0.05),PM合并ILD患者肌酶谱以肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)为主(P<0.05).④合并ILD的28例PM/DM患者经治疗,20例病情改善,8例重症7例均为DM合并ILD,5例治疗无效因Ⅰ型呼吸衰竭死亡(病死率占PM/DM合并ILD患者的17.9%).结论 ①首发症状为关节炎或关节痛,临床表现有关节炎或者关节痛、发热以及ESR和CRP高者易合并ILD;有特异性皮疹、AST升高的DM易合并ILD;肌酶以CK和CK-MB升高为主的PM易合并ILD.②DM合并ILD病情进展凶险,病死率高,预后不良.     

Ethnic differences in idiopathic pulmonary fibrosis: The Japanese perspective

Epidemiologic data suggest that there are ethnic differences between Japanese and other populations with regard to the important clinical aspects of interstitial lung disease (ILD), such as the cause of death and prognostic factors in patients with idiopathic pulmonary fibrosis (IPF). Acute exacerbation (AE) of IPF may be more common in Japan than in the rest of the world, although this suggestion remains controversial. Moreover, AE of ILD induced by gefitinib may also be more common in Japan, indicating that Japanese patients have a genetic vulnerability or susceptibility to AE. Recent large-scale studies are starting to reveal ethnic differences in the genetics of ILD, including the prevalence of the genetic polymorphisms associated with the clinical course of ILD. We anticipate that ongoing and upcoming research regarding ethnic differences will continue to provide valuable insights into the pathogenesis and management of ILD.     

Clinical evaluation of anti-aminoacyl tRNA synthetase antibodies in Japanese patients with dermatomyositis

OBJECTIVE: To investigate the distribution of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies among patients with autoimmune diseases, and to analyze the clinical features of patients with dermatomyositis (DM) with anti-ARS antibodies. METHODS: Serum samples from 315 patients with autoimmune diseases or related disorders who had visited Kanazawa University Hospital or affiliated facilities were assessed for anti-ARS antibodies by immunoprecipitation. In particular, the association between anti-ARS antibodies and clinical features was investigated in detail in patients with DM. RESULTS: Anti-ARS antibody was positive in 16 (29%) of 55 patients with DM, 2 (22%) of 9 patients with polymyositis, and 7 (25%) of 28 patients with idiopathic pulmonary fibrosis. Although anti-ARS antibody was detected with high frequency (63%, 15/24) in DM patients with interstitital lung disease (ILD), the incidence of anti-ARS antibody was very low (3%, 1/31) in DM patients without ILD. Anti-ARS antibody-positive patients with DM had significantly higher incidences of ILD (94% vs 23%) and fever (64% vs 10%) than the antibody-negative patients. Some immunosuppressive agents, in addition to oral corticosteroids, were required more frequently in the antibody-positive patients with DM than the antibody-negative patients (88% vs 26%). Although 60% of DM patients with ILD simultaneously developed ILD and myositis, ILD preceded myositis in 33% of patients. CONCLUSION: Among patients with DM, anti-ARS antibodies are found in a subset with ILD. DM patients with anti-ARS antibodies appear to have a more persistent disease course that requires additional therapy compared to those without anti-ARS antibodies.     

Interstitial lung disease in polymyositis and dermatomyositis

OBJECTIVES: To assess prevalence, characteristics, and long-term outcome of interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To determine predictive variables of ILD course in PM/DM, and to define both clinical and biochemical features associated with ILD onset in PM/DM. METHODS: The medical records of 156 consecutive PM/DM patients in 3 medical centers were reviewed. RESULTS: Thirty-six PM/DM patients (23.1%) developed ILD. We observed that 19.4% of patients with ILD had resolution of pulmonary disorders, whereas 25% experienced ILD deterioration. Morbidity and mortality rates were as high as 13.9% and 36.4%, respectively, in PM/DM patients with ILD. Parameters of PM/DM that related to ILD poor outcome were identified as follows: Hamman-Rich-like pattern, initial diffusing capacity of carbon monoxide <45%, neutrophil alveolitis, and histologic usual interstitial pneumonia. Additionally, for the group with ILD, polyarthritis, higher values of erythrocyte sedimentation rate and C-reactive protein, presence of anti-Jo-1 antibody, and characteristic microangiopathy were significantly more frequent. CONCLUSION: Our series underlines the high frequency of ILD in PM/DM patients, resulting in increased morbidity and mortality rates. It also indicates that PM/DM patients should routinely be screened for ILD, even those patients without anti-Jo-1 antibody, because 69% of our ILD patients were seronegative for the anti-Jo-1 antibody. Our findings further suggest that PM/DM patients presenting with factors predictive of ILD poor outcome may require more aggressive therapy.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

目的 检测类风湿关节炎(RA)患者血清骨桥蛋白(OPN)水平,分析血清OPN水平与RA疾病活动的相关性,初步探讨OPN在RA合并肺间质病变(ILD)发病机制中的作用.方法 收集临床确诊的65例RA患者血清.其中活动期RA患者43例,缓解期RA患者22例;其中合并ILD者24例,未合并ILD者41例.以20名健康体检者血清为健康对照组.采用酶联免疫吸附法(ELISA)检测血清OPN水平,并与RA患者的临床及实验室指标进行相关性分析.结果 ①RA组血清OPN水平(中位数18.0 ng/ml),高于健康对照组(中位数14.0 ng/ml,P<0.01);活动期RA组血清OPN水平(中位数20.0 ng/ml),高于缓解期RA组(中位数1.5 ng/ml,P<0.01).②RA组血清OPN水平与病程、关节压痛数、红细胞沉降率(ESR)、C反应蛋白(CRP)等呈显著正相关,与关节肿胀数无相关性.③RA合并ILD组血清OPN水平(中位数20.0 ng/ml),高于RA未合并ILD组(中位数17.0 ng/ml,P<0.05);且与动脉氧分压(PaO2)呈负相关;与肺功能(肺活量、一氧化碳弥散吸收率)无相关性.④RA合并ILD组关节压痛数,关节肿胀数、ESR、CRP等与RA未合并ILD组相比差异具有统计学意义(P均<0.01);RA合并ILD组血清类风湿因子(RF)(IgM)高于RA未合并ILD组(P<0.05).结论 OPN在RA发病机制中具有一定意义且与RA活动性有关,可作为评价疾病活动度的炎性指标;OPN参与了RA合并ILD的发生及进展,并与肺损害严重程度有关.     

Association of the RAGE/RAGE-ligand axis with interstitial lung disease and its acute exacerbation

The receptor for advanced glycation end product (RAGE) is a transmembrane receptor highly expressed in type 1 pneumocytes of healthy lungs. RAGE is considered to play a homeostatic role in the lung, as RAGE knockout mice develop lung fibrosis as they age. In contrast, RAGE can bind numerous ligands, including high-mobility group box 1 (HMGB1). These interactions initiate pro-inflammatory signaling associated with the pathogenesis of lung injury and interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF).ILD is a broad category of diffuse parenchymal lung disease characterized by various extents of lung fibrosis and inflammation, and IPF is a common and progressive ILD of unknown cause. The prognosis of patients with IPF is poor, and acute exacerbation of IPF (AE-IPF) is one of the main causes of death. Recent reports indicate that acute exacerbations can occur in other ILDs (AE-ILD). Notably, ILD is frequently observed in patients with lung cancer, and AE-ILD after surgical procedures or the initiation of chemotherapy for concomitant lung cancer are clinically important due to their association with increased mortality.In this review, we summarize the associations of RAGE/soluble RAGE (sRAGE)/RAGE ligands with the pathogenesis and clinical course of ILD, including IPF and AE-IPF. Additionally, the potential use of sRAGE and RAGE ligands as predictive markers of AE-IPF and cancer treatment-triggered AE-ILD is also discussed.     

来氟米特与类风湿肺间质病变

肺间质病变（ILD）是类风湿关节炎（RA）常见的关节外表现之一,发生率为7．7％,预后较差,近年来备受关注。而作为治疗RA的常用药物,来氟米特引起间质性肺炎的报道逐年增加,那么,RA合并ILD能否使用来氟米特呢？有文献指出来氟米特可以有效地治疗已经存在肺部疾病（包括甲氨蝶呤导致的间质性肺病）的RA患者,且未发现药物不良反应及肺部症状加重,因此指出当出现甲氨蝶呤相关ILD时,来氟米特可作为替代治疗用药。来氟米特在治疗中国RA患者的安全性是相对较好的,而近年来国外对于来氟米特引起ILD的报道却屡见不鲜。加拿大从一项治疗RA患者的队列研究中发现,应用来氟米特治疗的RA患者中ILD发病风险增高（校正RR1．9）,但其中元甲氨蝶呤用药史和ILD史的患者经来氟米特治疗后出现ILD的风险并未增高（校正RR1．2）。日本学者提出对于已有ILD或吸烟、高龄的男性RA患者应禁用或慎用来氟米特。文献报道不同种族RA患者对来氟米特并发的肺部不良反应存在差异,基因学检测将是寻找答案的关键。总之,虽然来氟米特有导致ILD的潜在隐患,但荟萃分析仍提示来氟米特治疗RA有很好的疗效及安全性,所以,对于已存在肺部疾患的RA患者,应分析具体病因慎重应用来氟米特,并定期监测肺CT。     

Interstitial lung disease and Sjögren’s syndrome in primary biliary cirrhosis: a causal or casual association?

Interstitial lung disease (ILD) has been reported in patients with primary biliary cirrhosis (PBC); however, its frequency and pathogenesis are still poorly documented. Sjogren's syndrome (SS) is fairly common among patients with PBC, but the relationship between SS and PBC also remains controversial. To determine whether ILD and SS in PBC is a causal or casual association, whether SS accompanying PBC, could be considered secondary to or associated with PBC. One hundred and nine consecutive PBC cases were analyzed, and the differences of clinical features, histological stages, and serum autoantibodies between the PBC patients with and without SS were compared. There were 46 PBC patients with SS and 63 without SS, and 11 patients met the criteria of ILD. SS is associated with PBC in the form of secondary SS. The frequency of ILD in PBC patients with SS was 21.7% while only 1.6% in PBC patients without SS (P < 0.0001). ILD in PBC was related to SS, with Spearman's rank coefficient of 0.330 (P = 0.000). The association of SS with PBC, significantly higher in patients with than without ILD, which supports the hypothesis that ILD and SS in PBC, may be a causal, not casual, association.     

Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD)

OBJECTIVE: Interstitial lung disease (ILD) may be a characteristic, often serious, manifestation of mixed connective tissue disease (MCTD). In this retrospective study, the frequency and clinical picture of ILD were determined in patients with MCTD using two diagnostic tests: high-resolution computed tomography (HRCT) and inhaled aerosol clearance times of (99m)Tc-labelled diethylene-triamine pentaacetate ((99m)Tc-DTPA). In addition, pulmonary function, effects of therapy and a variety of immunoserological markers were also assessed. METHODS: One hundred and forty-four consecutive patients with MCTD were selected from the clinic, irrespective of the presence or absence of ILD. All patients underwent a detailed clinical assessment, chest HRCT scanning, chest radiography, inhaled aerosol of (99m)Tc-DTPA clearance times, and all pulmonary function tests. Patients who had active ILD received corticosteroid (CS) or CS in combination with cyclophosphamide (CPH). All investigations were repeated after 6 months of immunosuppressive therapy. RESULTS: Ninety-six out of 144 MCTD patients (66.6%) had active ILD, 75 of this group (78.1%) showed ground glass opacity, 21 patients (21.8%) ground glass opacity with mild fibrosis with HRCT. Forty-five patients with active ILD received 2 mg/kg/day CS for 6-8 weeks alone and 51 patients CS in combination with CPH (2 mg/kg/day). Six months later, after therapy, 67 out of 96 MCTD patients with ILD (69.8%) showed a negative HRCT pattern, ground glass opacity with mild fibrosis developed in 15 patients (15.6%), and fibrosis was detected in 13 patients (13.5%). Only one patient showed subpleural honeycombing. (99m)Tc-DTPA was rapid in all 96 MCTD patients with active ILD (28.7 +/- 8.2 min, normal value >40 min). After therapy the (99m)Tc-DTPA was normalized, 79 out of 96 patients (82.3%). Carbon monoxide diffusion capacity (DLCO) was reduced in 33 out of 96 MCTD patients with active ILD (34.3%), while there were no significant differences in the pulmonary function tests between the active versus inactive stage of ILD or versus patients without ILD. The sera of 96 MCTD patients with active ILD contained a high level of immune complexes (ICs), and the total haemolytic complement levels (CH50/ml U) decreased. After 6 months of therapy, the IC levels decreased and CH50/ml levels normalized (MCTD patients before and after active ILD: IC optical density = 355 +/- 227 vs 206 +/- 92, P<0.001; CH50/ml, 38.0 +/- 12.6 U vs 64.3 +/- 13.0 U, P<0.001). CONCLUSIONS: HRCT is the gold standard for diagnosis of ILD. However, we used another method, (99m)Tc-DTPA, in order to compare this technique with HRCT. This latter technique has not been studied previously in MCTD. The elevated levels of IC and increased complement consumption indicated that IC-mediated alveolocapillary membrane damage and tissue injury might play a role in the pathogenesis of ILD in MCTD.     

Two cases with autoantibodies to small ubiquitin‐like modifier activating enzyme: A potential unique subset of dermatomyositis‐associated interstitial lung disease

The presence of anti‐aminoacyl tRNA synthetase (ARS) or anti‐melanoma differential‐associated gene 5 (MDA5) is strongly related to interstitial lung disease (ILD) in patients with dermatomyositis (DM). Several studies suggest a potential relationship between ILD and anti‐small ubiquitin‐like modifier activating enzyme (SAE) antibody in DM patients, but detailed clinical characteristics of anti‐SAE‐associated ILD still remain unknown. We have experienced 2 cases who were positive for anti‐SAE antibody, who presented with ILD in the context of clinically amyopathic DM. These 2 patients had the following common ILD characteristics: an insidious course with preserved pulmonary function; a limited extent of pulmonary lesions with subpleural peripheral‐dominant small ground glass opacity/consolidation on high‐resolution computed tomography; and a favorable treatment response. These findings suggest that anti‐SAE‐associated ILD is unique in terms of clinical and imaging features and differs from ILD associated with anti‐ARS or anti‐MDA5 antibody.