类风湿关节炎合并肺间质病变的发病相关因素

目的分析类风湿关节炎(RA)合并肺间质病变(ILD)的临床及实验室特点,探讨其发病相关因素。方法分析76例RA患者的临床资料,分为单纯RA组(n=40)和RA-ILD组(n=36),比较两组患者的一般情况、临床表现以及实验室指标。结果两组在年龄、关节肿痛数目、血管炎及发热阳性率、CRP、RF、IgM、白细胞计数比较差异具有统计学意义(P<0.05)。结论年龄大,RF高滴度表达,RA病情重,伴有关节外表现的RA患者易合并ILD,应尽早行高分辨CT等检查早期诊断及治疗。     

RA-ILD与临床和实验室指标相关性研究

目的收集类风湿关节炎合并肺间质病变(RA-ILD)患者的相关临床指标、实验室指标和肺部影像学表现等临床资料,分析这些因素与RA-ILD的发生和发展的关系,为RA-ILD的诊疗提供一定的临床依据。方法回顾性收集2014年1月-2015年1月在新疆维吾尔自治区人民医院风湿免疫科住院的RA患者,一般资料、临床表现、实验室指标和影像学检查。结果 1 204例RA患者中44例发生ILD,占21.6%。6例胸闷、气短;6例有咳嗽、咳痰;6例听诊有Velcro音。比较发现RA-ILD组咳嗽咳痰、胸闷气短、Velcro音的发生率高于单纯RA组(P0.05)。RA-ILD组患者肺HRCT最常见的表现是磨玻璃影。2 RA-ILD组的平均病程、年龄明显大于单纯RA组(P0.05)。3 RA-ILD组白细胞、血红蛋白、血小板、DAS28、ESR、CRP、C3、C4、RF、GPI较单纯RA组差异无统计学意义(P0.05)。4 RA-ILD组抗CCP抗体滴度显著大于单纯RA组(P0.05)。5比较两组AKA阳性率差异有统计学意义(P0.05),而抗SSA抗体阳性率、抗核抗体阳性率差异无统计学意义(P0.05)。结论 RA-ILD患者年龄大、平均病程长,大部分临床表现不明显,需及时完善HRCT,早期诊断和治疗。高抗CCP抗体滴度、ANA阳性可能与RA-ILD的发生相关。     

Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept

Abstract

Objective: To examine the deterioration of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with abatacept over the long-term.

Methods: We examined 131 patients with RA who had been treated with abatacept for more than 1 year. All patients underwent high-resolution computed tomographic (HRCT) scanning of the chest before administration of abatacept, and we examined deterioration of ILD over a follow-up period after administration of abatacept was initiated.

Results: Eleven patients (8.4%) showed deterioration of ILD over a mean follow-up period of 47.8 months. The factors related to ILD deterioration were use of methotrexate (MTX) [odds ratio 12.75, 95% confidence interval (CI) 1.09–148.77], and change in Krebs von-den Lungen-6 (odds ratio 1.00, 95% CI 1.00–1.01), according to multivariate logistic regression analysis.

Conclusion: MTX in patients with RA treated with abatacept was a risk factor for deterioration of ILD. Discontinuation of MTX should be considered one of treatment reduction to prevent the deterioration of ILD.     

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。     

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.     

Predictors of mortality in rheumatoid arthritis‐related interstitial lung disease

Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) has a heterogeneous clinical presentation and disease course. Establishing prognosis for these patients is challenging. Identifying the factors that predict mortality in patients with RA‐ILD could help guide management. A detailed systematic review was conducted in order to identify individual variables that predict mortality in RA‐ILD. A literature review was performed using keywords and medical subject headings to identify all articles relating to the prognosis of RA‐ILD. Studies were included if they identified predictors of mortality in adults with RA‐ILD, were published in English, and included at least 10 patients with RA‐ILD. Two authors independently reviewed each citation and extracted data from all studies meeting inclusion criteria. Any differences were then resolved by consensus. A total of 10 studies met our inclusion criteria. All were observational cohort studies of variable quality. Mean age of reported patients ranged from 55 to 69 years, and 41.7% of all patients were male. Median survival ranged from 3.2 to 8.1 years. Significant predictors of mortality on multivariate analysis were older age, male gender, lower diffusion capacity for carbon monoxide, extent of fibrosis, and the presence of usual interstitial pneumonia pattern. Mortality in RA‐ILD is associated with several patient‐ and ILD‐specific variables; however, previous studies are of low quality.     

IL-33在类风湿关节炎合并间质性肺炎患者中的表达及意义

目的探讨类风湿关节炎合并肺间质病变(RA-ILD)患者的临床血清中白介素-33(IL-33)表达,特征外周血单个核细胞(PBMC)。方法类风湿关节炎(RA)患者115例,分为RA-ILD组(29例)和RA组(86例),另选取健康自愿者20例为对照组,类风湿因子(RF)、抗环瓜氨酸抗体(anti-CCP)及抗角蛋白抗体(AKA)的浓度,检测PBMC中IL-33 mRNA表达,同时通过酶联免疫吸附法(ELISA)测定各组血清中IL-33的表达。结果与RA患者比,RA-ILD组除性别外平均年龄、病程比较差异均有统计学意义,RF、anti-CCP及AKA的浓度在RA-ILD与RA两组之间无统计学差异(P0.05),RA-ILD组PBMC中IL-33 mRNA及血清中IL-33表达含量明显比RA及正常对照组升高(P0.01)。结论 RA-ILD易发生于年龄大、病程较长的RA患者,一般实验检查不能预测RA患者ILD发生的可能性;PBMC和血清中IL-33可能与RA-ILD的发病有关;IL-33水平增高可能为RA-ILD的预测指标。     

Clinical and high resolution computed tomography characteristics of patients with rheumatoid arthritis lung disease

Introduction: Rheumatoid arthritis (RA) is a systemic disease of unknown cause. A variety of pulmonary disorders have been described in association with RA. Among the most common are interstitial lung disease (ILD) and bronchiectasis. Objectives: This study aims to determine the characteristics of RA patients with lung disease in relation to clinical characteristics, pulmonary function test (PFT) and high resolution computed tomography (HRCT) thorax. Method: This is a 6‐months cross‐sectional study involving 63 consecutive RA patients in an outpatient rheumatology clinic. Patients had a mean disease duration of 5 years and above. Disease activity and severity was assessed by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Articular Damage (RAAD) score. Full pulmonary function test (PFT) and HRCT of thorax were performed. Conclusions: The prevalence of RA‐ILD is 44% and 67% of patients are asymptomatic. There was significant higher proportion (68%) in patients of Chinese ethnicity who have ILD. Diffusion capacity of carbon monoxide was abnormal in all patients and forced expiratory flow (FEF)_25–75% was low in 16%. Restrictive pattern was 66.7% by PFT. The most common HRCT findings were reticulation (46%) followed by ground glass opacities (38.1%) and bronchiectasis (28.6%). There was no association between ILD and male gender, duration of the disease, smoking, rheumatoid factor, extra‐articular manifestations, disease activity or severity.     

High-resolution CT and pulmonary function tests in rheumatoid arthritis patients with subclinical interstitial lung disease in Kuwait

BackgroundInterstitial lung disease (ILD) is a frequent extra-articular manifestation of RA and can cause significant morbidity and mortality.Aim of the workTo characterize and define the frequency of radiological and functional abnormalities capable of identifying “subclinical” RA-ILD with particular concern to the effect of methotrexate (MTX) therapy.Patients and methodsSixty patients with RA were recruited with no respiratory manifestations. They were classified into two groups: group 1 included 35 patients receiving MTX and group 2 included 25 patients receiving only nonsteroidal anti-inflammatory drugs. Patients were also classified according to chest high resolution CT (HRCT) as RA-ILD or RA-noILD. Pulmonary function test (PFT) abnormalities were also used to further characterize occult respiratory defects.Results38.3% of RA patients had subclinical ILD (25% in group 1 and 13.3% in group 2), while 61.7% were RA-no ILD. The percentage of patients with RA-ILD was insignificantly more in group 1 than group 2 (42.9% and 32% respectively). HRCT score revealed minimal to mild involvement in both groups. Long-standing RA with mean articular duration >50 months carries a significant risk for ILD. Other variables as age, gender, smoking, disease activity or rheumatoid factor seropositivity were not significant risk factors for development of RA-ILD.ConclusionsLung involvement should always be considered in patients with RA particularly those on MTX therapy even in the absence of chest symptoms. A tight control by PFTs, chest radiography and/or HRCT is necessary. Further studies evaluating the potential effect of MTX on progressive ILD with RA are needed.     

类风湿性关节炎相关间质性肺疾病的研究进展

间质性肺疾病(interstitial lung disease,ILD)是类风湿性关节炎(rheumatoid arthritis,RA)常见的关节外病变和主要的死亡原因之一,早期诊治类风湿性关节炎相关间质性肺疾病(RA-ILD)直接影响RA患者预后。本文对近年RA-ILD的研究进展作简要概述,以期提高对该病的认识。     

305例结缔组织病相关间质性肺病临床特点分析

目的分析结缔组织病相关间质性肺病(Connective tissue disease associated interstitial lung disease,CTD-ILD)临床特征。方法回顾性分析305例西京医院临床免疫科CTD-ILD的临床特征及类风湿关节炎间质性肺病(Rheumatoid arthritis associated interstitial lung disease,RA-ILD)和干燥综合征间质性肺病(Sjogren's syndrome associated interstitial lung disease,p SS-ILD)患者胸部高分辨CT特点。结果 CTD患者ILD的发病率为11.78%,其中多发性肌炎相关ILD的发病率最高(53.13%),其次为抗中性粒细胞胞浆抗体相关性血管炎(40.74%)、混合结缔组织病(35.14%)和硬皮病(29.73%)。p SS-ILD和RA-ILD在CTD-ILD中所占比例最大,分别为24.92%和23.61%,两者约占所有CTD-ILD的一半。结论 CTD患者ILD的发病率高,RA-ILD和p SS-ILD是CTD-ILD的主要疾病,加强对CTD-ILD的早期筛查和早期治疗非常重要。     

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.