Diagnosis and prognostic value of restrictive ventilatory disorders in the elderly: a systematic review of the literature

Although less extensively studied compared to pulmonary obstructive diseases, restrictive lung disease (RLD) is highly prevalent and frequently disabling in the adult and, more, the elderly population. The underlying conditions may be either primarily pulmonary diseases, such as idiopathic pulmonary fibrosis, or non respiratory conditions secondarily affecting the lung, e. g. congestive heart failure, or else conditions affecting the lung expansion, e. g. obesity or rib cage deformity. The diagnosis is frequently based on the measurement of surrogate indexes such as the forced vital capacity (FVC) used as a proxy for total lung capacity (TLC). As a consequence, diagnosis of RLD is often characterized by poor specificity. In the elderly, worsening in the quality of life and poor prognosis are variably, but significantly, associated to RLD, being the underlying condition an important source of variability. Several causes of RLD are preventable and treatable conditions. A prompt identification of these conditions may allow to slow the decline of respiratory reserve and, thus, to preserve both personal independence and resistance to acute respiratory infections. This review gives an update on the latest evidence available on the prevalence and the prognosis of RLD in the elderly. Studies were identified through systematic searches of the electronic database MEDLINE. Reference list of eligible papers were also manually searched.     

Incidence and Mortality of Physician-Diagnosed Primary Sjögren Syndrome: Time Trends Over a 40-Year Period in a Population-Based US Cohort

Objective

To estimate the incidence and mortality rates, and their evolution over time, of physician-diagnosed primary Sjögren syndrome (pSS) in residents of Olmsted County, Minnesota.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.     

Liver abnormalities in connective tissue diseases

The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd–Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.     

Elevated level of circulating CD4+Helios+FoxP3+ cells in primary Sjogren’s syndrome patients

Objective: This study was designed to investigate the expression of regulatory T cells in primary Sjögren’s Syndrome (pSS) and to evaluate the clinical role of CD4?⁺?Helios⁺?FoxP3⁺ cells in pSS patients.

Methods: CD4?⁺?FoxP3^+?T cells in the peripheral blood of 39 pSS patients and 30 healthy controls were measured by flow cytometry and CD25 and Helios expression were also analyzed. The repression ability of CD4?⁺?CD25^hi cells was tested in vitro. Clinical information of pSS patients was retrospectively collected and their correlations with circulating Treg cells were analyzed. Cytokine levels in plasma were measured by ELISA and correlations with Helios⁺?FoxP3^+?cells were also detected.

Results: Circulating FoxP3^+?and Helios⁺?FoxP3^+?cells were elevated in pSS patients compared with controls. The suppression function of CD4?⁺?CD25^hi cells is not different between two groups. There are inverse correlations between Helios⁺?FoxP3^+?percentage and ESR, IgG, IgM and ESSDAI. Anti-SSB^? patients possess higher level of Helios⁺?FoxP3^+?cells than anti-SSB^+?patients. IL-6, IFNγ and IFNα levels were increased in pSS plasma and there were positive correlations between the levels of IFNγ/IFNα and percentage of Helios⁺?FoxP3^+?cells.

Conclusion: Circulating Helios ⁺?FoxP3⁺ cells were elevated in pSS patients and may contribute to suppressing autoimmunity in pSS patients.     

原发性干燥综合征合并间质性肺病的临床分析

目的探讨原发性干燥综合征合并间质性肺病(pSS-ILD)的发生情况、特征及早期诊断方法.方法对96例原发性干燥综合征患者(pSS),采用速率反射比浊法检测类风湿因子(RF)、C-反应蛋白(CRP)、血蛋白电泳、C3、C4;间接免疫荧光法和免疫印迹法检测抗核抗体(ANA)及其亚类.血气分析测定动脉血pH值、动脉血氧分压(PO2)、动脉血二氧化碳分压(PCO2).肺功能仪测定潮气容积(VT)、最大肺活量(VCmax)、用力肺活量(FVC)、第一秒用力呼气容积(FEV1)、最大呼气中段流量(MMFF)、最大通气量(MVV)和一氧化碳弥散功能(DLCO).放射学检查包括胸部正侧位X线片和肺高分辨CT(HRCT)扫描.结果本组pSS患者ILD的发生率为21.9%,易出现于抗SSA抗体阳性、RF高滴度、高γ球蛋白血症及临床活动期的患者;肺功能检测异常主要为弥散功能降低和限制性通气障碍;肺HRCT在发现pSS-ILD时优于普通X线胸片.结论pSS-ILD的发生与原发病的活动明显相关,肺弥散功能、HRCT对诊断pSS-ILD及判断预后具有重要价值;早期诊断与治疗的患者预后良好.     

路氏润燥汤治疗原发性干燥综合征3个月眼干症状疗效观察

目的探讨路氏润燥汤对原发性干燥综合征眼干症状的影响。方法将116例原发性干燥综合征气阴两虚型患者随机分为治疗组和对照组,每组58例,治疗组予中药路氏润燥汤,对照组予硫酸羟氯喹,治疗3个月后观察两组患者眼干症状VAS评分、中医证候积分、泪液及免疫、炎性指标改善情况,评价临床疗效。结果治疗组治疗后眼干症状VAS评分与治疗前比较,差异有统计学意义（P〈0．05）,对照组治疗前后比较差异无统计学意义（P〉0．05）;两组中医证候眼干症状积分治疗前后比较差异均有统计学意义（P〈0．05）;对照组血清免疫球蛋白IgG治疗前后比较,差异有统计学意义（P〈0．05）;两组吸墨试验、血清ANA、SSA、SSB、类风湿因子RF、血沉ESR治疗前后和组间比较,差异无统计学意义（P〉0．05）。结论路氏润燥汤对于原发性干燥综合征患者眼干症状改善明显,对泪液分泌、免疫及炎性指标改善不显著。     

Targeting primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Hallmarks of the disease are a loss of salivary and lacrimal gland function as well as lymphocytic infiltration, elevated proinflammatory cytokines, and circulating autoantibodies. Patients often experience significant fatigue and a decrease in their quality of life. Approximately 30–50% of pSS patients develop extra-glandular manifestations including malignant lymphoma. Although therapeutic approaches for pSS target both dryness and systemic manifestations, effective treatments are limited. However, new therapies targeting specific immune pathways associated with pSS are being developed. This review describes current and future targeted therapies against pSS.     

路氏润燥汤治疗原发性干燥综合征口干症状疗效对照研究

目的对比研究硫酸羟氯喹与路氏润燥汤对原发性干燥综合征口干症状的疗效。方法平均将116例原发性干燥综合征气阴两虚、瘀血阻络证患者随机分为治疗组和对照组,治疗组以润燥汤辨证加减治疗,对照组服用硫酸羟氯喹片,连续治疗3个月后,观察两组患者每月口干症状VAS评分、中医证候积分表症状评分、实验室检测指标改善情况及安全性指标。结果经3个月治疗后,治疗组口干症状VAS评分、中医证候积分与治疗前比较差异有统计学意义(P<0.01);实验室指标虽有改善,但与治疗前比较差异无统计学意义(P>0.05);安全性指标与治疗前比较差异无统计学意义(P>0.05)。治疗组治疗2、3个月后口干症状评分优于对照组(P<0.05,P<0.01)。结论路氏润燥汤对原发性干燥综合征患者口干症状的VAS评分、中医证候积分疗效满意,且安全可靠,但对非刺激性混合唾液流率、血清免疫球蛋白、类风湿因子及血沉改善疗效不明显。     

CD226 Gly307Ser association with multiple autoimmune diseases: A meta-analysis

Background

Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave’s disease, Wegener’s granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis.

Method

All eligible case-control studies were searched in the US National Library of Medicine’s PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association.

Results

7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine’s PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI = 1.12–1.27) by random effects model. Significantly increased risks were also observed in the South American (OR = 1.72, 95%CI = 1.34–2.20), Asian (OR = 1.46, 95%CI = 1.01–2.10), and European (OR = 1.29, 95%CI = 1.07–1.58). Similarly, significant associations were observed in two genetic models (OR = 1.41, 95%CI = 1.23–1.62 in a codominant model; OR = 1.33, 95%CI = 1.18–1.50 in a recessive model).

Conclusion

This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases.