A pilot trial of quantitative Tc-99m HMPAO and Ga-67 citrate lung scans to detect pulmonary vascular endothelial damage and lung inflammation in patients of collagen vascular diseases with active diffuse infiltrative lung disease

Diffuse infiltrative lung disease (ILD) includes a heterogeneous group of disorders predominantly affecting lung parenchyma and sparing the airway. To assess the degree of pulmonary vascular endothelial damage in active ILD, lung/liver uptake ratios (L/L ratio) on technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) lung scan were determined in 30 patients with active ILD. Meanwhile, the gallium-67 citrate (Ga-67) uptake index (GUI) on Ga-67 lung scan was used to evaluate the severity of lung inflammation in active ILD. In this study, high-resolution CT (HRCT) was used to evaluate disease activity in ILD. The results show statistically significant differences between normal controls and patients with active ILD as shown in L/L ratios and GUI. However, when the patients were divided into two groups of 15 patients with normal chest X-ray findings and 15 with abnormal X-ray findings, there was no significant difference in those parameters. In addition, there was no statistically significant difference between the groups in HRCT scoring. No good correlation between the degree of pulmonary vascular endothelial damage and the severity of lung inflammation was found. In addition, there were no good correlations between HRCT scoring vs GUI and HRCT vs L/L ratio in different study subgroups. In conclusion, L/L ratios on Tc-99m HMPAO and GUI on Ga-67 lung scans differ from chest X-ray findings and have the potential to detect the degree of pulmonary vascular endothelial damage and severity of lung inflammation in active IDL. However, the relationships between HRCT scoring, GUI, and L/L ratio in patients with collagen vascular diseases and active ILD are not significant.     

High-resolution computed tomography characterization of interstitial lung diseases in polymyositis/dermatomyositis

OBJECTIVE: Interstitial lung disease (ILD) associated with polymyositis (PM) and dermatomyositis (DM) sometimes progresses rapidly and is resistant to therapy. Clinical features that forecast the prognosis of the disease remain to be elucidated. Our aim was to assess if selected clinical features and high-resolution computed tomography (HRCT) findings can assist in predicting the clinical course of ILD in PM/DM. METHODS: We examined HRCT findings retrospectively for ILD identified in 17 patients with PM and 16 with DM. Radiological patterns and clinical features are analyzed in comparison with clinical course. RESULTS: Mortality rates were 12% and 44% for ILD associated with PM and DM, respectively. Most patients with DM died of rapidly progressive lung deterioration. No patient in the PM group died of respiratory failure. In the DM group, all patients with fatal ILD had ground-glass attenuation and reticular opacity as the principal radiological findings. Consolidation was recognized frequently as the principal pattern in nonfatal cases. Radiological patterns were categorized into 3 groups; A: consolidation dominant, B: ground-glass attenuation/reticular opacity dominant without chronic fibrosing process, and C: ground-glass attenuation/reticular opacity dominant with chronic fibrosing process. Occurrences of fatal disease were 0%, 83%, and 20%, in groups A, B, and C. CONCLUSION: The prognosis of ILD associated with DM differs from that with PM. The former can be classified into 3 subgroups on the basis of radiological findings, which are closely associated with clinical course.     

Interstitial lung disease in polymyositis and dermatomyositis: longitudinal evaluation by pulmonary function and radiology

OBJECTIVE: To estimate predictors and long-term outcome of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). METHODS: We conducted a prospective study in which newly diagnosed PM/DM patients, regardless of clinical symptoms of pulmonary disease, were investigated with repeated chest radiography, high-resolution computed tomography (HRCT) of the lungs, and pulmonary function test (PFT). Clinical, radiologic, and lung function outcome was based on the last followup results. RESULTS: Twenty-three patients with a mean followup period of 35 months were included. Findings on radiographic examination and/or PFT compatible with ILD were recorded in 18 patients (78%). Patients with ILD had lower lung function, higher radiologic scores, and higher creatine kinase values than those without ILD. All patients were treated with high-dose glucocorticoids and other immunosuppressive agents. Two patients died due to ILD, both with active myositis. During the followup, total lung capacity (TLC) improved in 33%, remained stable in 39%, and deteriorated in 28%. Changes in TLC correlated only partially with HRCT findings, which persisted even after normalizing for lung function. CONCLUSION: ILD associated with PM/DM is in most cases mild, chronic, and has a nonprogressive course during immunosuppressive treatment. PFT can be normalized during treatment with immunosuppressive therapy, even if radiologic signs of ILD persist. The course of ILD could not be predicted on the first examination. Therefore, myositis patients with ILD need careful evaluation of clinical features as well as PFT and radiologic features during followup.     

高分辨率CT及积分在结缔组织病并发间质性肺炎及预后中的价值

目的 比较不同结缔组织病(CTD)并发间质性肺炎(ILD)的肺高分辨率CT(HRCT)影像学特征,探讨肺HRCT积分对判断患者预后的预测价值.方法 回顾性收集117例各类CTD 临床资料和影像学资料以及随访结果,对肺HRCT病变进行评分,研究肺HRCT积分与患者预后的关系.结果 117例CTD患者中有95例在肺HRCT上显示有ILD,其中,系统性红斑狼疮(SLE)34%,类风湿关节炎(RA)31%,多发性肌炎/皮肌炎(PM/DM)9%,成人斯蒂尔病(AOSD)9%,干燥综合征(SS)5%,系统性硬化症(SSc)7%,混合性结缔组织病(MCTD)5%.CTD并发ILD肺HRCT最常见的表现是小叶间隔增厚,其次为毛玻璃样变,之后依次为不规则线状影或胸膜下线、网格影、支气管血管束增厚、马赛克灌注、蜂窝肺、薄壁囊肿、结节灶、大片实变病变、肺大泡.AOSD和SSc患者纤维化积分显著高于渗出积分(P＜0.05);CTD并发ILD患者5年生存率为48.5%(95%可信区间为22.4%～67.9%),纤维化积分≥2分是预测患者预后不良的危险因素(P=0.032),其敏感性为82%,特异性为87%.结论 不同CTD并发的ILD有不同的影像学特征,肺HRCT可以较好地发现并鉴别,肺HRCT纤维化积分可以判断患者的预后.     

应用一氧化碳弥散功能检测结缔组织病患者肺间质病变的意义

目的　探讨对结缔组织病 (CTD)患者肺间质病变 (ILD)进行早期、安全、有效且可量化的诊断方法。方法　对 93例CTD患者 ,其中 4 8例系统性红斑狼疮 (SLE)、18例皮肌炎 (DM)、2 1例系统性硬皮病 (PSS)、6例干燥综合征 (SS)进行了一氧化碳弥散功能检测 ,并与X线胸片、肺部高分辨率CT(HRCT)结果相比较 ;同时测定了 5 0名正常人的X线胸片和一氧化碳弥散功能作为对照。结果　X线胸片、肺部HRCT和一氧化碳弥散功能检测 (以一氧化碳弥散吸收率 <80 %为标准 )在SLE中检测到ILD的比率分别是 15 %、36 %和 4 2 % ;在DM中的比率分别是 17%、36 %和 39% ;在PSS中的比率分别是 38%、4 2 %和 5 2 % ;SS的比率分别是 33%、6 7%和 5 0 %。而正常人的X线胸片均正常 ,一氧化碳弥散吸收率均≥ 80 %。结论　X线胸片在检测CTD患者ILD中敏感性最低 ,而HRCT和一氧化碳弥散功能是检测CTD患者ILD的敏感方法。尤其是后者 ,具有敏感性高、不受X线照射、易被患者接受和对其损害程度进行量化等优点 ,既可作为早期了解CTD患者ILD的检测方法 ,又可通过一氧化碳弥散功能的改变对治疗效果进行评价。     

Two distinct clinical types of interstitial lung disease associated with polymyositis-dermatomyositis

Most patients with interstitial lung disease (ILD) associated with collagen vascular diseases (CVD) have a chronic indolent course with a relatively favorable prognosis; however, acute progression has been reported in some polymyositis-dermatomyositis patients. This study evaluated the prevalence, clinical features, and outcome relative to the presentation type of ILD in polymyositis-dermatomyositis (PM-DM). Ninety-nine patients with newly diagnosed polymyositis-dermatomyositis seen at the Asan Medical Center in Korea between January 1990 and December 2004 were enrolled. The clinical, radiological, and pathological findings were retrospectively reviewed. ILD were divided into acute (dyspnea within 1 month before diagnosis) or chronic types. ILD was found on chest radiographs in 33 patients (33.3%), and 11 (33.3%) of these were considered acute. The acute group presented with more severe respiratory symptoms, hypoxemia, and poorer lung function. Patients with an acute presentation had ground glass opacity and consolidation on high-resolution computed tomography (HRCT), in contrast to reticulation and honeycombing in the chronic type. Surgical lung biopsy of one acute-type patient revealed diffuse alveolar damage, whereas biopsies in the chronic type showed usual interstitial pneumonia (UIP) in four cases and nonspecific interstitial pneumonia (NSIP) in another four. Eight acute-type patients (72.7%) died of respiratory failure within 1-2 months despite steroid therapy. The 3-year mortality rate of the chronic-type patients (21.2%) was not statistically significantly different from that of the patients without ILD (10.2%). In polymyositis-dermatomyositis, the acute, severe form of ILD was not infrequent.     

Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in diffuse infiltrative lung disease

BACKGROUND: Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders which predominantly affect the lung parenchyma and spare the airway. OBJECTIVE: To assess pulmonary vascular endothelium damage in ILD, the lung uptake of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) was determined. METHODS: In 20 ILD patients and 25 controls without ILD, the lung uptake of 99mTc-HMPAO was measured. Anterior lung imaging, including a large part of the liver, was made 10 min after intravenous injection of 20-25 mCi of 99mTc-HMPAO. Regions of interest covered the liver and lung to calculate the lung/liver uptake ratios. The 20 ILD patients included 10 patients with clinically manifest pulmonary disease (group 1) and 10 asymptomatic patients (group 2). All of the study subjects had normal pulmonary function test results. RESULTS: The mean lung/liver uptake ratio in the 25 controls without ILD (0.36 +/- 0.10) was significantly lower than that in the 20 ILD patients (0.97 +/- 0.61). In addition, the mean lung/liver uptake ratio in the 10 ILD patients with clinically manifest pulmonary disease (1.45 +/- 0.51) was higher than that of the other 10 asymptomatic ILD patients (0.49 +/- 0.09). CONCLUSIONS: Our results indicated that determining the lung/liver uptake ratio on 99mTc-HMPAO lung imaging should be an objective method to assess subclinical pulmonary damage in ILD patients.     

皮肌炎多发性肌炎患者间质性肺病病理资料推断性分析

目的 分析皮肌炎(DM)、多发件肌炎(PM)合并间质性肺病(ILD)患者的胸部X线、胸部高分辨CT(HRCT)及肺功能等肺部表现临床特点及其预后.方法 回顾性分析上海长海医院风湿免疫科1999年1月至2007年1月期间收住院的33例DM/PM合并ILD除外感染患者的临床资料.结果 33例ILD患者经胸部X线及HRCT证实.根据临床-影像学特点并结合血气分析、肺功能测定,参照美国胸科学会和欧洲呼吸协会问质性肺炎的分类诊断标准,推断分析病理类型主要为非特异性间质性肺炎(NSIP)(57%)和寻常性间质性肺炎(UIP)(25%). UIP类型预后差、病死率高(70%).结论 结合患者的影像学资料、肺功能、血气分析推断病理类型主要为NSIP和UIP,其中UIP病死率高、预后差.     

Capillaroscopy is a dynamic process in mixed connective tissue disease

To determine the clinical relevance of 'scleroderma-pattern' (SD-pattern) in mixed connective tissue disease (MCTD), 63 (MCTD) patients (Kasukawa's criteria) were consecutively selected. The main inclusion criterion was availability of previous nailfold capillaroscopy (NC) five years before inclusion. At entry, organ involvement and autoantibody evaluation were performed. The mean age and disease duration were 45.3 +/- 10 and 8.45 +/- 5.42 years, respectively. SD-pattern was observed in 41 patients at entry (65%) and in 45 at previous NC (71.5%), P = 0.20. Ten patients (16%) changed NC, seven normalized, and three developed SD-pattern. Disease duration, number and frequency of organ involvement were similar in patients with and without SD-pattern. In contrast, analysis of each SD-pattern parameter revealed a significantly lower frequency of moderate/severe avascular areas (AA) at entry compared to previous examination (26.5 versus 53%, P = 0.013). Moreover, 76% of patients with interstitial lung disease (HRCT) had AA at entry, whereas only 24% of patients with this alteration did not have this NC finding (P = 0.017). Furthermore, reduced capillary density was more frequently observed in patients taking immunosuppressive therapy than in those without this medication (66.7 versus 33.3%, P = 0.001). NC in MCTD is a dynamic process and analysis of each SD-pattern parameter seems to be a good indicator of lung involvement and disease severity.     

Short‐term and long‐term outcomes of interstitial lung disease in polymyositis and dermatomyositis: A series of 107 patients

Objective

This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) and to determine variables predictive of ILD deterioration in PM/DM.

Methods

Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high‐resolution computed tomography (HRCT) scan.

Results

ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n = 20), patients with progressive‐course lung signs (n = 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n = 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid‐refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%).

Conclusion

Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome.

     

Utility of lung ultrasound to identify interstitial lung disease: An observational study based on the STROBE guidelines

Lung ultrasound (LUS) has recently been used to identify interstitial lung disease (ILD). However, data on the role of LUS in the detection of ILD remain limited. The aim of this study was to investigate the diagnostic value of LUS compared with high-resolution computed tomography (HRCT) in patients with ILD.The retrospective study was carried out by reviewing the medical records of patients with respiratory signs and symptoms discharged from the respiratory ward. Only patients with suspected ILD who underwent HRCT and LUS within a week were selected. ILD was identified with a semi-quantitative score of B-lines >5 and a Warrick score >0 points. The endpoints of LUS in diagnosing ILD (i.e., sensitivity, specificity, positive likelihood ratio [PLR], negative likelihood ratio [NLR], positive predictive value [PPV], and negative predictive value [NPV], and receiver operating characteristic [ROC] curve) was compared with that of HRCT. The reference standard used for the diagnosis of ILD was based on history, clinical findings and examination, and laboratory and instrumental tests, including pulmonary function tests, lung histopathology, and HRCT (without LUS findings).The final clinical diagnosis of ILD was 55 in 66 patients with suspected ILD. HRCT was positive in 55 patients, whereas LUS detected ILD in 51 patients. Four patients with negative LUS findings were positive on HRCT. The results showed 93% sensitivity, 73% specificity, 3.40 PLR, 0.10 NLR, 94% PPV, and 67% NPV for LUS, whereas 100% sensitivity, 82% specificity, 5.49 PLR, 0.01 NLR, 97% PPV, and 100% NPV for HRCT. Comparison of the 2 ROC curves revealed significant difference in the diagnostic value of the 2 methods for the diagnosis of ILD (P = .048).Our results indicated that LUS is a useful technique to identify ILD. Considering its non-radiation, portable and non-invasive advantages, LUS should be recommended as a valuable screening tool in patients with suspected ILD.     

Anti-MDA5 antibody dermatomyositis-associated rapidly progressive interstitial lung disease patient complicated with mixed connective tissue disease: A case report

Anti-MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP-ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71-year-old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti-Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti-MDA5⁺DM-RP-ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite “triple therapy” for RP-ILD. This case illustrates that patients with coexisting anti-MDA5⁺DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti-Ro52 antibodies.     

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.     

Clinical decision rule to predict the presence of interstitial lung disease in systemic sclerosis

Objective

To develop a clinical decision rule to predict the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc; scleroderma) and to estimate the prevalence of SSc‐ILD.

Methods

Patient data were extracted from the Canadian Scleroderma Research Group registry. Three algorithms for the clinical decision rule were considered based on lung auscultation, chest radiography (CXR), and % predicted forced vital capacity (FVC). High‐resolution computed tomography (HRCT) scans were used as the gold standard to determine the diagnostic properties of the 3 algorithms. Multiple imputation was used to impute HRCT data when missing, thereby avoiding bias due to differential referral for HRCT.

Results

This study included 1,168 patients. Of the patients with HRCT scans, 65% had evidence of ILD, compared to 26% by physical examination and 22% by CXR. The FVC of those who did not have HRCT was 8.8% greater than those who did (95% confidence interval [95% CI] 6.0–11.6%). Algorithm A, which identified the presence of ILD based on crackles on lung auscultation and/or findings on CXR, had a likelihood ratio of 3.9, compared to 3.2 for Algorithm B (which included patients with FVC <70%) and 2.2 for Algorithm C (which included patients with FVC <80%). The prevalence of ILD in the cohort was estimated to be 52% (95% CI 46–59%).

Conclusion

We developed a simple clinical decision rule to predict SSc‐ILD with good test characteristics. The prevalence of ILD in a large, unselected SSc cohort was estimated to be 52%.     

Esophageal involvement and pulmonary manifestations in systemic sclerosis

OBJECTIVE: To assess whether esophageal manometric motor disturbances are associated with abnormalities consistent with interstitial lung disease (ILD) on both pulmonary function tests (PFT) and high resolution computerized tomography (HRCT) scans in patients with systemic sclerosis (SSc), during initial evaluation and at 2 years followup. METHODS: Esophageal manometry, PFT, and HRCT scans were performed in 43 consecutive SSc patients. PFT and HRCT scan parameters were compared between patients with severe esophageal motor dysfunction (i.e., aperistalsis and decreased low esophageal sphincter pressure), patients with moderate esophageal motor dysfunction (hypoperistalsis), and patients without esophageal motor dysfunction on manometry. RESULTS: During initial evaluation of SSc, patients with severe esophageal motor impairment, compared with those with moderate and without esophageal dysmotility, exhibited significantly decreased median values of diffusing capacity for carbon monoxide (DLco) (68% vs. 94% vs. 104%) and exhibited higher prevalence of evidence for ILD on HRCT scan (57% vs. 27% vs. 18%). At 2 years followup of SSc, patients with severe esophageal motor disturbances, compared with those without, had faster deterioration of DLco median values (-16% vs. +1%) and higher frequency of ILD on HRCT scan (70% vs. 25%). CONCLUSION: Our series underscores a correlation between the degree of esophageal manometric motor disturbances and evidence for ILD on PFT and HRCT scan in SSc patients, suggesting that gastroesophageal reflux (GER) may be one of the contributing factors of ILD in SSc. Our findings further indicate that patients with severe esophageal impairment may require closer followup of lung parameters. In turn, it suggests that aggressive therapy of GER should be initiated in these SSc patients, as it may result in decreased deterioration of pulmonary function.     

Increased serum concentration of BAFF/APRIL and IgA2 subclass in patients with mixed connective tissue disease complicated by interstitial lung disease

Abstract

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD?). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD? patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF–APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD? patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD? patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD.     

HIGH RESOLUTION COMPUTED TOMOGRAPHY OF THE LUNGS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INTERSTITIAL LUNG DISEASE

We performed high resolution computed tomography (HRCT) on thelungs of 20 patients with RA and clinical and radiological evidenceof interstitial lung disease (ILD). A case control group ofpatients with RA but without evidence of ILD were similarlystudied and all patients underwent detailed pulmonary functiontesting. Clinical findings, drug therapy, smoking status, thepresence/absence of SS and disease activity were also assessed. HRCT showed a range of abnormalities among patients thoughtto have ILD. Interstitial fibrosis was confirmed in 16 but wasfrequently associated with emphysema. Ground glass opacificationwas present in seven, while basal honeycombing was also evidentin seven patients. Both these features were present in two patientswith ILD. Bronchiectasis was identified in six patients andwas the predominant finding in two patients previously thoughtto have ILD. Among the control patients, HRCT was normal inonly five. Clinically unsuspected ILD was present in four patients,while a further four had bronchiectasis. Pleural disease wasidentified in seven controls. Pulmonary function tests weregenerally poor predictors of HRCT findings, although a reducedresidual volume (RV) [>1 S.D.] was 83% specific for the presenceof ILD and a raised RV [>1 S.D.] was 64% specific for emphysema.Smoking did not correlate with the presence of either ILD oremphysema and there were no correlations between disease activityand HRCT findings. RA patients with evidence of ILD have abnormalities on HRCTwhich cannot be confidently predicted on any other non-invasivetest. Some degree of abnormality is common even in patientswithout apparent lung disease. HRCT may offer a useful non-invasivemeans of assessing RA patients with apparent ILD. KEY WORDS: Rheumatoid arthritis, Interstitial lung disease, High resolution computed tomography     

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.     

结缔组织病肺间质病变的临床特点及治疗效果分析

目的探讨不同结缔组织病肺间质病变（CTD-ILD）的临床特点和治疗效果。方法分析82例CTD-ILD患者的临床特征及胸部高分辨CT（HRCT）特点并观察治疗后HRCT的变化。结果（1）SSc—ILD的发生率最高，为70．0％。其次为pSS—ILD、PM／DM-ILD、RA—ILD、SLE—ILD，系统性红斑狼疮继发的ILD（SLE—ILD）发病年龄（26．2±7．8）较其他CTD-ILD早（P〈0．05）。RA—ILD、SSc—ILD病程较长，pSS—ILD、SLE一[LD和PM—ILl）病程较短。RA．ILD出现活动后气促少见（P〈0．05）。pSS—ILD出现呼吸道症状（40％）和体征（50％）最多见。85．7％SSc-ILD出现雷诺现象，支持雷诺现象与ILD相关。（2）SLE—ILD以磨玻璃影多见，丽蜂窝状改变较少；pSS-ILD以蜂窝状改变和纵隔淋巴结肿大相对较多。（3）大部分患者治疗后肺部间质病变吸收好转（56．7％），其中88．2％SLE—ILD吸收好转，28．4％患者肺部病变处于静止，14．9％患者间质病变较前进展。结论CTD—ILD患者一旦确诊，应尽早用激素联合免疫抑制剂治疗。     

Plasma free amino acid pattern in chronic hepatitis as a sensitive and prognostic index

To evaluate the diagnostic and prognostic significance of plasma amino acid imbalance in chronic hepatitis (CH), plasma-free neutral amino acid levels were examined in 47 patients with CH, consisting of 8 chronic persistent hepatitis (CPH), 26 chronic aggressive hepatitis (CAH) 2A and 13 CAH 2B, compared with those of 58 patients with liver cirrhosis (LC) and of 12 healthy controls. Fischer's ratio (a molar ratio of branched chain amino acids to aromatic amino acids) was found to be reduced in the order of normal subjects (3.5 +/- 0.4), CPH (3.0 +/- 0.2), CAH2A (2.7 +/- 0.3), CAH2B (2.1 +/- 0.3), compensated LC (LC-C, 1.5 +/- 0.4) and decompensated LC (LC-D, 1.1 +/- 0.2). Patients with CPH showed a significant decrease of the ratio compared with normal subjects (P less than 0.05). The ratio was significantly higher in patients with CAH 2B in comparison with LC-C (P less than 0.001). Especially, the ratio could be used to discriminate the three distinct stages of CH. Discriminant analysis, carried out using six amino acids, Fischer's ratio and conventional liver function tests indicated that Fischer's ratio was the most reliable parameter for differentiation of the three stages of CH. Furthermore, serial examinations of Fischer's ratio in patients with CH remained unchanged in CPH, whereas was significantly reduced in CAH during 2-3 years follow-up. These results strongly suggest that Fischer's ratio is a useful indicator for differential diagnosis and for prediction of the subsequent clinical course of CH as well as being a sensitive index for functional hepatic reserve in chronic active liver diseases.