弥漫性肺疾病的疾病谱分析

目的通过对我科收治的471例弥漫性肺疾病的分析,总结其疾病谱的特点,以提高对弥漫性肺疾病的认识。方法统计分析2003年1月1日~2007年12月31日我科收治的471例弥漫性肺疾病患者,根据各种疾病的诊断标准进行归类。结果在471例弥漫性肺疾病患者中,特发性间质性肺炎184例,继发于免疫结缔组织疾病的间质性肺炎109例,特殊类型及其它病种94例,恶性肿瘤44例,感染相关40例。结论广义的间质性肺炎占弥漫性肺疾病的绝大多数,诊断中首先根据临床表现和辅助检查排除免疫结缔组织病,依据病理检查诊断各种特发性间质性肺炎,但应特别注意,约近20%的患者其病因仍是最为常见的肿瘤和感染,仅仅因其表现不典型而被延误诊治。     

具有自身免疫特征的间质性肺炎的研究进展

具有自身免疫特征的间质性肺炎是指一类具有潜在的自身免疫性临床特征但不符合结缔组织病诊断标准的特发性间质性肺炎。随着这一名称及其诊断标准的提出,世界多中心开展一系列队列研究。通过查阅近5年来国内外文献,本文就疾病的临床表现、血清学、形态学等方面展开讨论并总结特点,可能为临床诊治提供新的思路和见解。     

结缔组织病相关性间质性肺疾病的诊治进展

结缔组织病（CTD）是一组累及全身多系统的自身免疫病,合并间质性肺疾病（ILD）较为常见,导致肺功能障碍、低氧血症,严重影响患者的生活质量和预后。不同CTD显示出异质性的ILD类型。CTD-ILD常见的影像学和组织病理学类型是非特异性间质性肺炎、机化性肺炎和普通型间质性肺炎。大部分CTD-ILD表现为缓慢进展的肺损伤,少数患者短期内急剧进展且预后不良。CTD-ILD目前主要应用糖皮质激素和／或免疫抑制剂治疗,生物制剂显示出临床疗效,尚需随机临床试验证实。部分ILD患者具有自身免疫病的特征,不足以诊断为某种特定的CTD,应予以密切随访。     

未分化结缔组织病

未分化结缔组织病（UCTD）又称为未分化风湿病（URD）。1980年LeRoyetal最早提出未分化结缔组织综合征（UCTS）的概念,针对该病引起了风湿病学者们的广泛研究。直至1989年,Mosca等提出了UCTD的概念,并建立了UCTD的初步分类标准且被用于临床。本病具有多个结缔组织病的临床和免疫学实验室特点,但又不能满足任何一种特定疾病;换言之,这些临床与实验室特点是与某种分类位置的结缔组织病相关,被定义为一种独立的临床诊断疾病。     

特发性肺纤维化概念变迁:从特发性肺纤维化到多种疾病实体相关的不可逆性肺纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)作为成人病因未明、纤维化性、进行性发展的致死性疾病已得到广泛关注。2018年ATS/ERS/JRS/ALAT临床实践指南强调影像学和组织病理学表现为寻常型间质性肺炎(UIP)是其标志性特征。然而所谓UIP的特征并不特异。多种间质性肺疾病包括结缔组织病、纤维化性或慢性过敏性肺炎、职业性间质性肺疾病结节病、药物相关间质性肺疾病等均可表现为UIP。目前尚无准确的方法或标志物可将IPF的UIP与其他类型间质性肺疾病的UIP区分开来。     

未分化结缔组织病导致的肝损害

目的 研究未分化结缔组织病(undifferentiated connective tissue disease,UCTD)导致肝损害的临床特征及其诊断和治疗.方法 对一例UCTD导致肝损害患者的病史、临床表现、实验室检查、诊断治疗经过以及近期疗效进行回顾性分析.结果 患者为中年女性,临床表现为乏力、食欲减退、低热、皮疹,合并有间质性肺炎、心包积液等,有"骨关节炎"膝关节置换术等病史,血清转氨酶升高,血IgG、球蛋白升高,ESR增快,嗜酸粒细胞水平明显升高,血ANA 1:320阳性,肝脏病理特点符合结缔组织病所致的小血管炎.经小剂量泼尼松治疗后,临床症状和实验室检查指标好转,近期疗效显著.结论 对于结缔组织病患者肝功异常的鉴别诊断应该想到UCTD导致肝损害的可能,对于肝功能损害明显、常规保肝治疗无效的患者可应用小剂量糖皮质激素治疗.     

间质性肺疾病的主要检验手段及评价

弥漫性让质性肺疾病（ diffuse interstitial lung disease, DILD）是一组异源性疾病,病变主要累及肺泡壁和肺泡周围组织。病因可分为两类,一类为已知原因,另一类为未知病因。DILD临床诊断困难,特别是特发性间质性肺炎,其临床、影像和病理特征的认识还不一致,随着对这类疾病认识的提高,针对DILD的检查方法有了很大的发展,提高了诊断成功率,我们将对此类疾病的主要检查方法及进展做一介绍。     

结缔组织病相关间质性肺疾病的临床研究进展

结缔组织病（CTD）是一组累及全身多系统的慢性炎症性自身免疫病,其共同病理变化为淋巴细胞致敏产生免疫损伤,导致血管壁、间质的纤维素样坏死性炎症及随后引起多脏器的胶原纤维增生。由于肺间质、肺血管、支气管及胸膜均富含疏松结缔组织和血液供应,CTD常累及肺和胸膜,引起间质性肺疾病（ILD）、肺血管炎和胸膜炎等。     

结缔组织疾病与肺间质疾病4例报告

间质性肺疾病 (IL D)是一组具有相似临床表现、X线胸片改变及肺功能损害的异质性疾病的总称。病理特点为弥漫性肺泡炎、肺实质炎和间质纤维化。典型临床表现包括渐进性劳力性气促、干咳 ,双下肺吸气末捻发音或湿罗音、杵状指 ,胸片示双肺弥漫性网格状影 ,最终可导致严重的双肺纤维化 (蜂窝肺 )及呼吸衰竭。本组疾病病因复杂 ,结缔组织疾病是肺间质性疾病的一个重要原因 ,许多结缔组织疾病在其病程中均可累及肺脏 ,有的甚至以肺部表现为首发症状或因肺部表现而就诊。本文讨论近年来以肺间质疾病收住我科 ,而最终确诊为结缔组织疾病的四个病…     

纤维支气管镜肺活检诊断弥漫性肺疾病160例临床分析

目的 探讨纤维支气管镜肺活检用于诊断弥漫性肺疾病(DLD)的应用价值和安全性.方法 回顾性分析我院近10年160例DLD患者接受支气管镜肺活检(TBLB)的临床和病理诊断资料.结果 160例DLD患者中行TBLB确诊49例(30.63%),病理诊断包括其中特发性间质性肺炎18例,肺部恶性肿瘤10例,肺结核6例,结缔组织病相关DLD 4例,结节病3例,嗜酸性细胞性肺炎2例,放射性肺炎、机化性肺炎、气道淀粉样变、肺泡蛋白沉积症、肺淋巴管肌瘤病各1例,其他不能归类间质性肺炎1例;女性患者明显多于男性(92 vs 68,P<0.01),DLD中特发性间质性肺炎最多,TBLB其术后并发症少,术后肺功能无明显变化.结论 TBLB是诊断DLD的安全有效的方法,对DLD的鉴别诊断具有重要意义.     

Differenzialdiagnose interstitieller Lungenerkrankungen

In recent years, substantial progress has been made regarding the classification of idiopathic interstitial pneumonia (IIP) and the treatment of idiopathic pulmonary fibrosis (IPF). As the treatment of IPF is different from that of other IIPs, it has become more important to correctly diagnose other fibrotic IIPs. In 2015, an ERS/ATS task force proposed the term “interstitial pneumonia with autoimmune features” (IPAF) in order to create a consensus regarding the nomenclature and classification criteria for an interstitial pneumonia suggestive of an underlying autoimmune cause without, however, fulfilling the definitive criteria for a connective tissue disease (CTD). The treatment options are currently immunosuppressive agents, but prospective data are still missing.     

Idiopathic interstitial pneumonias with connective tissue diseases features: A review

A systematic approach is recommended to search for clinical and biological features of connective tissue disease (CTD) in any patient with interstitial lung disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be considered particularly in women and subjects younger than 50 years, and in those with an imaging and/or pathological pattern of non‐specific interstitial pneumonia. However, the diagnosis of CTD may be difficult when ILD is the presenting or the dominant manifestation of CTD. A proportion of patients with ILD present symptoms that belong to the spectrum of CTD and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some imaging and histopathological patterns may also suggest the presence of an underlying CTD. Although studies published to date used heterogeneous definitions and terminology for this condition, evidence is accumulating that even limited CTD features are relevant regarding symptoms, imaging features, pathological pattern and possibly evolution to overt CTD, whereas the impact on prognosis needs confirmation. Conversely, autoantibodies alone do not seem to impact the prognosis or management in patients with otherwise typical idiopathic pulmonary fibrosis and no extra‐pulmonary manifestation. A collective international multidisciplinary effort has proposed a uniform definition and criteria for ‘interstitial pneumonia with autoimmune features’, a condition characterized by limited CTD features occurring in the setting of ILD, with the aim of fostering future clinical studies. Referral of ILD patients suspect to have CTD to a rheumatologist and possibly multidisciplinary discussion may contribute to a better management.     

Clinical features,risk factors,and outcomes of patients with interstitial pneumonia with autoimmune features: a population-based study

To investigate the clinical features, risk factors and outcomes of patients with interstitial pneumonia with autoimmune features (IPAF). A total of 1429 patients with idiopathic interstitial pneumonia (IIP) and undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD) were screened to identify patients who met IPAF criteria. Clinical, serological, and morphological features of patients with IPAF were characterized. Outcomes between patients with IPAF, UCTD-ILD, and IIP who were divided into idiopathic pulmonary fibrosis (IPF) and non-IPF groups were compared using survival as an endpoint. Patients with IPAF were much common in young female and had lower percentage of ever smoking and a significantly shorter survival than those with non-IPAF (P?<?0.001). Subgroup analysis revealed that IPAF cohort survival was worse than that in non-IPF (P?<?0.001), but better than that in IPF (P?<?0.001). In IPAF cohort, the most common systemic symptom and serological abnormality were Raynaud’s phenomenon (12.9%) and ANA ≥?1:320 (49.2%); the most frequent high-resolution computed tomography (HRCT) pattern was nonspecific interstitial pneumonia (NSIP) (61.6%). Multivariate analysis indicated that several factors including age, smoking history, organizing pneumonia (OP) pattern in HRCT, and anti-RNP positivity were independently associated with significantly worse survival. IPAF had the distinct clinical features and outcomes compared with other groups of ILD. Additional studies should be needed to explore the underlying autoimmune mechanism and to determine risk stratification in future clinical research.     

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality

Background and objective

Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome.

Methods

Patients with prior UCTD‐interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all‐cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features.

Results

One hundred and one UCTD‐ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud’s phenomenon, positive anti‐nuclear antibody (ANA) and non‐specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features.

Conclusion

Current IPAF criteria encompassed the majority of broadly defined UCTD‐ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

     

血清抗中性粒细胞胞质抗体阳性肺间质病患者临床及预后分析

目的探究血清抗中性粒细胞胞质抗体(ANCA)阳性的间质性肺疾病患者的临床特点及预后。方法回顾性纳入2006年3月至2016年3月就诊于北京协和医院的间质性肺疾病患者274例,其中男81例,女193例,年龄(53±11)岁,根据诊断分为血清ANCA阳性肺间质病(ANCA-ILD)、结缔组织病相关性肺间质病和自身免疫特征的间质性肺炎(CTD-ILD/IPAF)及特发性间质性肺炎(IIP)组,分析3组患者在临床表现、血清学、肺功能、影像学、生存及复发方面的差异。结果274例患者中ANCA阳性38例(38/274,14%),发病年龄(59±10)岁,随访时间(52±31)个月,死亡7例(7/38,18%)。ANCA阳性患者发病年龄高于CTD-ILD/IPAF[(52±10)岁]和IIP[(53±11)岁,H=19.29,P<0.001],血红蛋白[(129±21)mg/L]低于CTD-ILD/IPAF[(138±15)mg/L]和IIP[(140±19)mg/L,H=8.17,P=0.017],ESR[(46±35)mm/1 h]高于CTD-ILD/IPAF[(26±24)mm/1 h]和IIP[(19±22)mm/1 h,H=19.73,P<0.001],治疗后肺功能FVC改善率(31%)低于CTD-ILD/IPAF(59%)和IIP(39%,χ^2=11.74,P=0.003),胸部CT病变吸收率(61%)低于CTD-ILD/IPAF(82%)和IIP(67%,χ^2=9.23,P=0.010),病死率(18%)高于CTD-ILD/IPAF(6%)和IIP(12%,χ^2=7.16,P=0.028)。结论ANCA阳性患者与其他类型肺间质病患者在临床特征方面存在差异,治疗效果不佳,预后较差。     

结缔组织病相关间质性肺病的诊治策略

结缔组织病(connective tissue disease,CTD)是一组全身性自身免疫性疾病,病变累及多种脏器。由于肺和胸膜均富含胶原、血管等结缔组织,因此 CTD 大多可以损伤肺和胸膜等呼吸系统多个器官,包括：呼吸肌、胸膜、肺血管、气道、肺实质和肺间质,且部分患者呼吸道表现为首发症状。间质性肺病(interstitial lung disease,ILD)在 CTD 中十分常见,发生率在数个 CTD 病种中超过50%。与之相对应,15%~30%初诊为特发型间质性肺炎(idiopathic interstitial pneumonia,IIP)的患者最终被确认符合 CTD-ILD 诊断。ILD 是导致 CTD 患者死亡的重要原因之一。CTD 包括包括系统性红斑狼疮(SLE)、类风湿性关节炎(RA)、原发性干燥综合征(pSS)、多发性肌炎(PM)、皮肌炎(DM)、系统性硬化(SSc)和混合性 CTD (MCTD)等。本文就 CTD-ILD 的诊治策略作一简要综述。     

IPAF should receive early treatment for sharing similar clinical characteristics as CTD-ILD: a report from 273 Chinese patients

Clinical Rheumatology - The clinical characteristics of interstitial pneumonia with autoimmune features (IPAF) and connective tissue disease interstitial lung disease (CTD-ILD) have not been...     

Prevalence of Myositis-Specific Antibodies in Idiopathic Interstitial Pneumonias

Although included in the serological domain of the ‘interstitial pneumonia with auto-immune features’ (IPAF) research statement, the search for myositis-specific antibodies (MSA) is not incorporated in routine clinical practice. The objective of the study was to evaluate MSA prevalence in an idiopathic interstitial pneumonia (IIP) cohort (n?=?68) with suggestive morphological interstitial lung disease patterns. Twelve of 68 patients (17.6%) carried MSA, whereof only two were anti-nuclear antibody-positive. Besides female gender, no demographic or pulmonary function parameter was predictive for MSA positivity. MSA were present in 32.4% of IPAF patients (n?=?37), being essential for IPAF diagnosis in four of them (10.8%).     

The development of connective tissue diseases in patients with autoimmune hepatitis: a case series

OBJECTIVES: To study the prevalence of connective tissue diseases (CTD) in patients with autoimmune hepatitis (AIH). METHODS: We identified 11 cases of AIH over the past 7 years at our institution, through a systematic chart review of patients with this diagnosis. Their charts were reviewed for the development of systemic CTD. RESULTS: Three of the 11 patients with a definitive diagnosis of AIH developed systemic CTD. All were white: 2 women and 1 man, with an age range of 33 to 62 years, and with disease duration of 1 to 7 years. One patient developed systemic lupus erythematosus (SLE) with vasculitis and peripheral neuropathy. The second developed limited scleroderma and the third developed undifferentiated connective tissue disease (UCTD) and interstitial lung disease. There appear to be shared susceptibility alleles for AIH and CTD in addition to the shared positive autoantibodies. CONCLUSIONS: Patients with AIH may be at increased risk for developing systemic CTD. Conversely, a review of the literature reveals that patients with systemic CTD may be at increased risk of developing AIH. Patients with either AIH or CTD should be monitored for further development of concurrent autoimmune diseases.     

Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease?

RATIONALE: The American Thoracic Society/European Respiratory Society International Consensus Classification panel identified the clinical entity idiopathic nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis and recommended further study. OBJECTIVES: We hypothesized that idiopathic NSIP is an autoimmune disease and the lung manifestation of undifferentiated connective tissue disease (UCTD), a recently described, distinct entity. METHODS: We studied 28 consecutive patients with idiopathic interstitial pneumonia (IIP) enrolled in the University of California, San Francisco Interstitial Lung Disease Center who met prespecified criteria for UCTD, as follows: at least one clinical manifestation of connective tissue disease, serologic evidence of systemic inflammation in the absence of clinical infection, and absence of sufficient American College of Rheumatology criteria for another connective tissue disease. Medical record reviews, evaluation of radiographs, and scoring of lung biopsies were performed. The control group consisted of all other patients (n = 47) with IIP who did not meet the UCTD criteria. MEASUREMENTS AND MAIN RESULTS: The patients with UCTD were more likely to be women, younger, and nonsmokers than the IIP control subjects. Compared with the control group, patients with UCTD-ILD were significantly more likely to have ground-glass opacity on high-resolution computed tomography (HRCT) and NSIP pattern on biopsy, and less likely to have honeycombing on HRCT or usual interstitial pneumonia on biopsy. At our center, the majority of patients classified as idiopathic NSIP (88%) met the criteria for UCTD. CONCLUSIONS: Most patients diagnosed with idiopathic NSIP meet the case definition of UCTD. Furthermore, these results show that the clinical entity idiopathic NSIP is different from idiopathic pulmonary fibrosis and appears to be an autoimmune disease.