Progressive preclinical interstitial lung disease in rheumatoid arthritis

BACKGROUND: Early detection and treatment for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objective of this study was to identify asymptomatic lung disease and potential therapeutic targets in patients having RA and preclinical ILD (RA-ILD). METHODS: Sixty-four adults with RA and 10 adults with RA and pulmonary fibrosis (RAPF) were referred to the National Institutes of Health, Bethesda, Maryland, and underwent high-resolution computed tomography (HRCT) and pulmonary physiology testing. Proteins capable of modulating fibrosis were quantified in alveolar fluid. RESULTS: Twenty-one of 64 patients (33%) having RA without dyspnea or cough had preclinical ILD identified by HRCT. Compared with patients without lung disease, patients with RA-ILD had statistically significantly longer histories of cigarette smoking (P< .001), increased frequencies of crackles (P= .02), higher alveolar-arterial oxygen gradients (P= .004), and higher HRCT scores (P< .001). The HRCT abnormalities progressed in 12 of 21 patients (57%) with RA-ILD. The alveolar concentrations of platelet-derived growth factor-AB and platelet-derived growth factor-BB were statistically significantly higher in patients having RA-ILD (mean [SE], 497.3 [78.6] and 1473 [264] pg/mL, respectively) than in patients having RA without ILD (mean [SE], 24.9 [42.4] and 792.7 [195.0] pg/mL, respectively) (P< .001 and P=.047, respectively). The concentrations of interferon gamma and transforming growth factor beta(2) were statistically significantly lower in patients having RAPF (mean [SE], 5.59 [1.11] pg/mL and 0.94 [0.46] ng/mL, respectively) than in patients having RA without ILD (mean [SE], 14.1 [1.9] pg/mL and 2.30 [0.39] ng/mL, respectively) (P=.001 and P=.006, respectively) or with preclinical ILD (mean [SD], 11.4 [2.6] pg/mL and 3.63 [0.66] ng/mL, respectively) (P=.04 and P=.007, respectively). Compared with patients having stable RA-ILD, patients having progressive RA-ILD had statistically significantly higher frequencies of treatment using methotrexate and higher alveolar concentrations of interferon gamma and transforming growth factor beta(1) (P=.046, P=.04, and P=.04, respectively). CONCLUSIONS: Asymptomatic preclinical ILD, which is detectable by HRCT, may be prevalent and progressive among patients having RA. Cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD. Quantification of alveolar proteins indicates that potential pathogenic mechanisms seem to differ in patients having RA-ILD and symptomatic RAPF.     

类风湿关节炎合并肺间质病变的临床特点

目的 分析类风湿关节炎（RA）合并肺间质纤维化（ILD）患者的临床特点,为尽早发现和诊断RA-ILD提供有价值的临床信息.方法 回顾性分析2008年1月～2009年1月于我院就诊的40例RA-ILD患者与42例未合并ILD的RA患者的临床资料,并对两组患者的临床资料加以比较.结果 RA-ILD组患者多数以咳嗽为首发症状,全部患者高分辨率CT检查均存在不同程度的ILD表现.RA-ILD组患者的病程、晨僵时间长于未合并ILD的RA组患者（P＜0.05）.RA-ILD患者组的DAS28评分、血沉、C反应蛋白、抗环瓜氨酸（CCP）抗体、Ro-52阳性率高于未合并ILD的RA组患者（P均＜0.05）.结论 RA-ILD患者多数以咳嗽为首发症状,高分辨率CT能较早的提示ILD并评价其严重程度.RA病程、活动性、炎性指标、抗CCP抗体及抗Ro-52可能是与RA-ILD密切相关的重要指标.     

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease

BackgroundPlatelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD.MethodsThe study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany.ResultsiPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity.ConclusionsOur results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.     

Assessment of interstitial lung disease among black rheumatoid arthritis patients

Clinical Rheumatology - Conflicting reports exist regarding the racial and the gender distribution of rheumatoid arthritis–related interstitial lung disease (RA-ILD). In a major population...     

类风湿关节炎相关间质性肺疾病的早期诊断及药物治疗进展

间质性肺疾病是类风湿关节炎患者最常见关节外表现,病死率高.类风湿关节炎相关间质性肺疾病的病因及治疗效果尚不明确.本文就其早期诊断与药物治疗作一综述,以期改善其预后.     

Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis

OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population-based epidemiologic study. METHODS: A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case-control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The reports of ILD associated with leflunomide use are likely the result of channeling of high-risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.     

HLA DR antigens and disease expression in rheumatoid arthritis.

Ninety-four patients with rheumatoid arthritis who possessed one or more of the HLA DR alloantigens 2, 3, or 4 were studied to investigate the genetic influence on disease severity and prognosis. In those with a disease duration of less than 10 years radiological damage was less in patients with DR2 than in those without this antigen. When current joint scores were compared, patients with this antigen had less evidence of disease than patients with DR3 or 4, DR3 patients having the highest scores. The presence of nodules and Sjögren's syndrome were less common in the DR2 patients. Variability in response to disease modifying drugs according to the patient's HLA DR antigen status may explain these differences. It is concluded, however, that possession of HLA DR2 may be an indicator of good prognosis in patients with rheumatoid arthritis.     

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。     

Imaging findings in interstitial lung disease

Imaging is an essential step in the management of patients with interstitial lung disease, contributing to detection, diagnosis, evaluation of pulmonary damage and prognosis, surveillance, and screening for complications. The chest x-ray is the fundamental examination. High-resolution computed tomography is often useful, particularly for severe forms and for cases of difficult diagnosis. It should not however be used as a routine examination for the initial work-up nor repeated systematically. Computed tomography is more contributory to the diagnosis of subacute or chronic interstitial pneumonia than for acute forms. We present here the different imaging methods, the role of imaging in chronic and acute interstitial pneumonia, and discuss the main computed tomographic signs of chronic interstitial lung disease.     

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.     

血清白细胞介素-33与类风湿关节炎合并肺间质病变相关性研究

目的 分析类风湿关节炎(RA)合并肺间质病变(ILD)患者血清白细胞介素(IL)-33及其受体人基质裂解素2(ST2)的表达情况及与肺功能等实验室指标的相关性,为其早期诊断提供依据.方法 收集2012年3月至2013年3月在我科初诊为RA患者245例,分为RA-ILD组58例与单纯RA组187例,观察各组肺功能等相关实验室指标,另收集我院体检中心健康体检者60名为健康对照组.采用酶联免疫吸附试验(ELISA)法测定以上各组的血清IL-33及ST2浓度水平.组间比较采用两样本t检验;多组间比较采用多个样本均数比较的方差分析;IL-33浓度及相关变量间比较采用Pearson相关分析.结果 RA患者ILD发生率为23.7％(58/245).与健康对照组[(85±38) pg/ml]相比,RA[(433±42) pg/ml]及RA-ILD [(746±43) pg/ml]患者中血清IL-33水平显著增高,差异有统计学意义(P＜0.01);且与RA组患者相比,RA-ILD组患者血清IL-33及ST2水平升高更为明显(P＜0.01).RA-ILD组患者肺活量占预计值百分比(VC％)、用力肺活量占预计值百分比(FVC％)、最大呼气中段流量占预计值百分比(MMF％)和一氧化碳弥散量(DLCO)多项肺功能指标均较RA组患者明显降低,差异有统计学意义(P＜0.01).IL-33浓度与各实验室指标相关性比较:IL-33浓度与类风湿因子呈正相关(r=0.82,P＜0.01),且与抗环瓜氨酸多肽抗体(ACPA)滴度呈正相关(r=0.55,P＜0.01),而其与DLCO呈负相关(r=-0.80,P＜0.01).结论 IL-33参与RA的发病过程,且可能与RA-ILD的发病相关.     

类风湿关节炎肺间质病变相关因素的临床分析

目的探讨类风湿关节炎(RA)肺间质病变(RA-ILD)的发生率及相关因素。方法对资料完整的352例住院RA患者进行回顾性分析,根据诊断分为有ILD组和无ILD组,比较分析RA-ILD发生的相关因素。结果 2005-12～2007-10住院RA患者ILD的发生率为5.1%。单因素分析相关因素为年龄、血免疫球蛋白G异常及双手X线Ⅲ/Ⅳ级改变。多因素多元逐步Logistich回归分析,相关因素为年龄和血免疫球蛋白G异常。结论类风湿关节炎肺间质病变发生率高,是多种因素共同作用的结果。