Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia

OBJECTIVE: The aim of this study was to evaluate the efficacy of cyclosporin A (CsA) in patients with interstitial pneumonia (IP). DESIGN: Retrospective comparative study. PATIENTS: We reviewed 33 patients (23 males and 10 females with a mean age of 62.5 years) with histologically-proven progressive IP who were treated with CsA. All patients had corticosteroid-resistant IP or developed acute exacerbation of IP in their courses. RESULTS: The underlying systemic diseases were: idiopathic interstitial pneumonias (IIPs) in 19 patients, and collagen vascular diseases (CVDs) in 14. The histopathological patterns and underlying diseases of IP were classified as usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) in 10 patients, cellular-nonspecific interstitial pneumonia (NSIP)/IIPs in 3, fibrotic-NSIP/IIPs in 5, organizing pneumonia (OP)/IIP in 1, UIP/CVDs in 4, cellular-NSIP/CVDs in 7, fibrotic-NSIP/CVDs in 2, and diffuse alveolar damage (DAD)/CVD in 1, respectively. They received a low dosage of CsA combined with corticosteroids. The prognoses after treatment with CsA were well correlated with histopathological patterns. Cellular-NSIP and OP showed better prognoses than fibrotic-NSIP, UIP or DAD. In addition, CVDs had better prognoses than IIPs, when compared on the basis of the same histopathological patterns. Furthermore, the prognoses in the CsA-treated group were significantly better than in those without CsA treatment in regard to acute exacerbation of UIP/IPF. CONCLUSIONS: CsA combined with corticosteroids may be an efficacious treatment for corticosteroid-resistant IP and for acute exacerbation of IPF.     

Nonspecific interstitial pneumonia: a real clinical entity?

Based on the current multidisciplinary classification of idiopathic interstitial pneumonia (IIP) organized by ATS/ERS, nonspecific interstitial pneumonia (NSIP) is considered as one type of IIP. An incidence of idiopathic NSIP is relatively small and possesses clinical features that are different than idiopathic pulmonary fibrosis (IPF) and usual interstitial pneumonia (UIP). Because there is little evidence of a long-term prognosis in patients with NSIP, some of them have an unfavorable prognosis similar to IPF/UIP. We review the significance of prognostic factors that have been reported in patients with IPF/UIP by applying them to patients with NSIP. The association with collagen vascular diseases focuses on etiologic background. Finally, the article discusses whether NSIP could be an early lesion of UIP based on the reported evidence and our own professional experiences.     

Comparison of bronchoalveolar lavage fluids from nonspecific interstitial pneumonia and from ordinary interstitial pneumonia]

We studied cell findings in the bronchoalveolar lavage fluid (BALF) of 13 patients with nonspecific interstitial pneumonia (NSIP) and 20 with ordinary interstitial pneumonia (UIP). NSIP and UIP were difficult to distinguish by high-resolution CT. Surgical lung biopsies were performed in all patients. We divided the patients with NSIP and UIP into 4 groups, a group of idiopathic NSIP (idiopathic NSIP), a group of NSIP patients associated with collagen vascular disease (CVD NSIP), a group of idiopathic UIP patients (idiopathic UIP) and a group of UIP patients associated with collagen vascular disease (CVD UIP). We then examined the differences in BALF cell findings between these groups. The percentage of lymphocytes in BALF was higher in idiopathic NSIP and CVD NSIP than in the healthy control. The percentage of alveolar macrophages was lower and the percentage of lymphocytes was higher in CVD NSIP than in idiopathic UIP. The CD4/CD8 ratio in BALF of idiopathic NSIP was lower than with idiopathic UIP. It is important that NSIP be distinguished from UIP clinically, and our results suggest that BALF cell findings may be useful for making this distinction.     

Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?

The lung is frequently involved in connective tissue diseases (CTDs), although the frequency of lung manifestations varies according to the type of CTD. Interstitial lung diseases (ILD) are frequently seen in CTDs, particularly systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), accounting for a significant proportion of deaths. A large percentage of patients with CTD-associated ILD has limited and stable disease, not requiring treatment. However, a significant minority has severe and/or progressive disease, necessitating prompt initiation of treatment. CTD-ILD histological patterns include non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP). NSIP is the most common pattern in all CTDs, except for RA, characterized by a higher frequency of UIP. ILD can present acutely or chronically, with acute presentations being more common in systemic lupus erythematosus and PM/DM. Idiopathic pulmonary fibrosis (IPF) is a progressively worsening ILD characterized by inflammation and fibrosis. The characteristic histological pattern of IPF is UIP. Interestingly, a UIP pattern is associated with a significantly better survival in CTD-related disease compared to the idiopathic variety. Prognosis in IPF is dismal, with a median survival since diagnosis of 2-3 years. No treatment regimen has been shown to improve survival in IPF. By contrast, although there have been only two randomized placebo-controlled trials investigating the effect of immunosuppressive treatment in SSc-associated ILD, clinical experience suggests that immunosuppressive drugs in CTD-related ILDs are capable of benefiting a significant proportion of patients, particularly those with certain histological patterns of disease. This review will essentially focus on CTD-associated ILD and will compare aspects of clinical presentation and management to those of IPF.     

BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia.

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking and treatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.     

Inflammatory cell phenotyping of the pulmonary interstitium in idiopathic interstitial pneumonia

BACKGROUND: Several studies have implicated the role of inflammation in the pathogenesis of lung damage in idiopathic interstitial pneumonias (IIPs). Investigations of inflammatory cells in IIP have show that eosinophils, neutrophils and T cells may be associated with a poorer prognosis. OBJECTIVES: The aim of our study was to map, by quantitative analysis, the number of inflammatory cells in the lung tissue of patients with non-specific interstitial pneumonia/non-specific interstitial pneumonia (NSIP/NSIP), acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) and to correlate them with lung function tests and survival. METHODS: After immunohistochemical staining, we quantified the content of inflammatory cells [macrophages, neutrophils (elastase+), plasma cells, and CD3, CD4 and CD8 T lymphocytes (TLs)] in 20 NSIP, 20 DAD and 20 UIP surgical lung biopsies. RESULTS: The total density of inflammatory cells was significantly increased in DAD and NSIP when compared to UIP (p = 0.04). TLs were increased in DAD and NSIP when compared to UlP lungs (p < 0.05). The density of inflammatory cells in UIP showed significant differences in normal, intervening and dense fibrosis areas (p < 0.05). The most numerous cells infiltrating the mural fibrosis and honeycombing areas were plasma cells, neutrophils (elastase+), CD20+, CD3+, CD4+ and CD8+ (p < 0.05). In UIP, CD3+ TLs were directly correlated with forced expiratory volume in 1 s/forced vital capacity ratio x 100 (p = 0.05). CD68+ cells presented a significant positive correlation with the forced expiratory volume in 1 s (p = 0.04); neutrophil (elastase+) cells significantly correlated with residual volume (p = 0.02), residual volume/total lung capacity (p = 0.04) and carbon monoxide transfer factor (p = 0.03). The most important predictor of survival in UIP was CD3+ TLs (p = 0.05). CONCLUSION: The total density of inflammatory cells and lymphocytes presents a different distribution within the pulmonary parenchyma in AIP/DAD, NSIP/NSIP and IPF/UIP evolutionary adapted responses to injury. There is a localized distribution of inflammation in the normal, intervening and dense fibrosis areas of UIP for CD3+, associated with a lethal deterioration of the pulmonary function and poor survival. Our findings provide further evidence of the importance of inflammation in the pathophysiology of IIPs.     

Acute and subacute idiopathic interstitial pneumonias

Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE‐IPF) and AE‐NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug‐induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody‐targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value‐laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.     

Fibrotic idiopathic interstitial pneumonia: high-resolution computed tomography considerations

The fibrotic idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). The characteristic high-resolution computed tomography findings of UIP are reticular abnormality and honeycombing with basal and peripheral predominance. Honeycombing is the strongest predictor of UIP. The extent of fibrosis on computed tomography (CT) is an important prognostic indicator in idiopathic pulmonary fibrosis (IPF). When ground-glass attenuation is seen in IPF it commonly progresses to fibrosis and honeycombing. Imaging may help to detect complications of IPF, including accelerated progression, lung cancer, and secondary infection. Our understanding of the clinical and radiological features of NSIP is still evolving. The CT finding of extensive ground-glass abnormality and some reticular abnormality, with basal and peripheral predominance, is strongly suggestive of NSIP. However, the CT appearances of NSIP overlap with those of UIP, organizing pneumonia (OP), and desquamative interstitial pneumonia (DIP), and biopsy may be necessary to sort this out. Other idiopathic pneumonias that may be associated with CT evidence of lung fibrosis include DIP, OP, acute interstitial pneumonia, and lymphoid interstitial pneumonia.     

Intermittent intravenous cyclophosphamide pulse therapy for the treatment of active interstitial lung disease associated with collagen vascular diseases

The availability of intravenous cyclophosphamide (CYC) pulse therapy for collagen vascular diseases (CVD)-associated interstitial lung disease (ILD) has been indicated. However, the standard protocol concerning the dosage and the interval of CYC infusion has not yet been established. The aim of this study is to elucidate the efficacy and the safety of our "divided administration" protocol of CYC for the treatment of CVD-ILD. The treatment protocol consists of two steps: step 1, CYC 400-500 mg at 10-day intervals for at least 30 days, and step 2, CYC 500 mg at 14-day intervals for at least 4 weeks. The ILD activities were monitored by respiratory symptoms, serum levels of KL-6 (a serological marker of IP), chest computed tomography (CT), and pulmonary function tests. Seventeen patients [nonspecific interstitial pneumonia (NSIP), 12 patients; usual interstitial pneumonia (UIP), 4; lymphocytic interstitial pneumonia (LIP), 1] accomplished the study protocol. The sessions of CYC infusion ranged from 5 to 20 (mean, 8.3). In all patients, respiratory symptoms were improved and the serum levels of KL-6 were decreased (from 1572 +/- 904 to 978 +/- 392 U/ml; P < 0.01). Chest CT findings were improved in 4 patients (23.5%): they were all classified as NSIP; not deteriorated, 13 patients (76.5%). An improvement in the vital capacity percentage (%VC) was recognized in 10 patients (78.6%) and in diffusing capacity of carbon monoxide (%DLco) in 8 patients (61.5%). Nevertheless, mean %VC and mean %DLco did not change significantly. No major adverse event(s) occurred. The efficacy and safety of our "divided administration" protocol of CYC for CVD-ILD was demonstrated.     

Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias

STUDY OBJECTIVES: To determine the prevalence and prognostic significance of histologic discordance in multiple lung biopsy specimens obtained from patients investigated for suspected cryptogenic fibrosing alveolitis (CFA)/idiopathic pulmonary fibrosis (IPF). METHODS: and results: Between 1984 and 2001, 64 patients undergoing investigation for CFA/IPF were identified in whom multiple biopsies were performed that showed either a pattern of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP). These cases were classified into three groups: concordant UIP-UIP (n = 25, 39.1%), discordant UIP-NSIP (n = 8,12.5%), and concordant NSIP-NSIP (n = 31, 48.4%). The discordant UIP group had survival, clinical, and physiologic features similar to those of the concordant UIP group, and prognosis in both concordant and discordant UIP groups was significantly worse than that of the concordant NSIP group (p = 0.02 and p = 0.04, respectively). The age of the concordant UIP group was higher than that of the concordant NSIP group, with the mean age of the discordant group being intermediate. There were no significant differences among the three groups in smoking history, duration of dyspnea, presence or absence of crackles, FVC, diffusion capacity of the lung for carbon monoxide, or PaO(2). CONCLUSIONS: Patients with discordant UIP-NSIP results on multiple biopsies show clinical behavior similar to those with concordant UIP-UIP and should be regarded as having CFA/IPF in the correct clinical context, rather than "idiopathic NSIP" for the purposes of management. Multiple biopsies should be considered in all patients in order to improve the prognostic information provided by lung biopsy.     

Cyclosporin A treatment of interstitial pneumonia]

To assist in making prognoses for patients with interstitial pneumonia (IP) who were treated with cyclosporin A (CsA), we conducted a review of forty-nine patients (32 men and 17 women with a mean age of 62 yrs) with progressive IP during the period from 1997 through 2001. All patients were steroid-resistant or acutely exacerbated cases. They received a low dosage of CsA (100-130 mg/day) combined with corticosteroids. Before and after the CsA therapy, blood gas analysis and HRCT scans were evaluated. Twenty-five patients underwent video-assisted thoracoscopic surgery (VATS) or autopsy for a histopathological evaluation. Among the 49 patients with IP, the documented underlying systemic diseases were of unknown etiology (IPF or IIP) in 26 and were collagen vascular diseases (CVD) in 23. The chest CT pattern and underlying systemic diseases of IP were classified as a usual interstitial pneumonia (UIP) pattern/IPF in 16 cases, a non-UIP pattern/IIP in 10 cases, a UIP pattern/CVD in 7 cases, and a non-UIP pattern/CVD in 16 cases. The prognoses after CsA treatment were improved or unchanged in 27% of cases with a UIP pattern/IPF, 78% of cases with a non-UIP pattern/IIP, 71% of cases with a UIP pattern/CVD and 75% of cases with a non-UIP pattern/CVD; deteriorated in 73%, 22%, 29% and 25% of cases, respectively, with these patterns and underlying diseases. At present, four out of thirteen (31%) patients with acute exacerbation of UIP pattern/IPF have survived for four to twelve months (mean: 7.5 months). Four patients revealed re-exacerbation of IP after the dose of CsA was tapered. Among the 25 patients with IP, the histopathological patterns of IP were classified as usual interstitial pneumonia (UIP) in 10 cases, nonspecific interstitial pneumonia (NSIP) in 14 cases (group I, 2; group II, 5; group III, 7) and diffuse alveolar damage (DAD) in 1 case. The prognoses were improved or unchanged in all cases of NSIP group I, in 80% of cases with NSIP group II, in 29% of cases of NSIP group III and in 20% of cases of UIP; and deteriorated in the case of DAD, in 80% of cases of UIP, in 71% of cases of NSIP group III, and in 20% of cases of NSIP group II. It should be emphasized that CsA combined with corticosteroids may be effective for the treatment of steroid-resistant or acute exacerbation cases of IP. Further studies are required to determine long-term outcome with this treatment.     

Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease

STUDY OBJECTIVES: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia. DESIGN: Retrospective review. SETTING: Two thousand-bed, university-affiliated, tertiary referral center. PATIENTS: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD. METHOD: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared. RESULTS: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively. CONCLUSIONS: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.     

Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance

Background and Aims: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. Materials and Methods: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. Results: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r_s = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV₁)/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. Conclusion: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival. Please cite this paper as: Parra ER, Noleto GS, Tinoco LJM, Capelozzi VL. Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance. The Clinical Respiratory Journal 2008; 2: 227–238.     

Usual interstitial pneumonia: idiopathic pulmonary fibrosis versus collagen vascular diseases

BACKGROUND: Bronchoalveolar lavage fluid (BALF) lymphocytosis was found in patients with usual interstitial pneumonia (UIP) associated with collagen vascular diseases (CVD) other than diffuse systemic sclerosis (SSc), but it was not found in patients with idiopathic pulmonary fibrosis (IPF), a disease histologically diagnosed as UIP. This difference could be partly due to variations of UIP spectrums between IPF and interstitial pneumonia associated with CVD. METHODS: We scored histopathological findings of lung specimens obtained from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a semiquantitative scoring method. All cases were diagnosed as UIP by surgical lung biopsy. None of the patients were current smokers. RESULTS: Compared with IPF and SSc cases, CVD patients without SSc presented decreased scores of fibrosis (p < 0.01) and alveolar space cellularity (severity, p < 0.05). Lymphocytes were mainly localized in the alveolar walls and the majority of cells in the alveolar spaces were macrophages. On the other hand, other scores such as cellularity and alveolar wall cell infiltrate did not vary among these three groups. CONCLUSION: Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than in patients with IPF/UIP and UIP-SSc.     

Classification and recent advances in idiopathic interstitial pneumonia

Idiopathic interstitial pneumonia (IIP) is a heterogeneous group of diseases comprising acute interstitial pneumonia, bronchiolitis obliterans organizing pneumonia (BOOP), nonspecific interstitial pneumonia, desquamative interstitial pneumonia, and idiopathic pulmonary fibrosis and usual interstitial pneumonia (IPF/UIP). We review the clinicopathological spectrum of IIP and introduce recent advances in classification, treatment, and prognosis. BOOP can be clinically categorized as an interstitial pneumonia, though prominent granulation tufts are seen in the airspaces. Though differences between the nonspecific interstitial pneumonia and other lips can be histopathologically clarified, the focus of clinical research on NSIP is differentiation from BOOP, or from IPF and UIP. IIP can be categorized into two groups: groups with acute or subacute lung injuries or fibrosis, such as in acute interstitial pneumonia, BOOP and nonspecific interstitial pneumonia, and groups with chronic injuries or fibrosis, such as IPF/UIP. This classification accords well with the maturity of fibrosis, CT findings, bronchoalveolar lavage fluid cell findings, and prognosis. The most critical problem is the treatment of IPF/UIP, because of its high mortality.     

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.     

普通型间质性肺炎和非特异性间质性肺炎肺组织中不同细胞因子的表达及其意义

目的　研究转化生长因子 (TGF) β1、碱性成纤维细胞生长因子 (b FGF)、白细胞介素 8(IL 8)、白细胞介素 13(IL 13)、γ干扰素 (IFN γ)在普通型间质性肺炎 (UIP)和非特异性间质性肺炎(NSIP)肺组织中的分布、表达及意义。方法　经胸腔镜或开胸肺活检获取 5例UIP和 8例NSIP患者的肺组织。对照组 5例 ,来自手术切除的远离肺癌原发灶的周边肺组织。用免疫组化法半定量分析细胞因子的分布及表达。结果　TGF β1、IL 8、b FGF主要分布在肺泡上皮细胞、肺泡巨噬细胞、细支气管上皮细胞 ,UIP组表达强于NSIP组和对照组。IL 13主要分布在肺泡上皮细胞、肺泡巨噬细胞、间质单个核细胞 ,UIP、NSIP组表达无明显差异 ,但均强于对照组。IFN γ主要分布在间质单个核细胞 ,NSIP组表达强于UIP组和对照组。UIP组的IL 13/IFN γ比值为 (2 18± 0 76 ) ,NSIP组为(0 95± 0 2 8) ,对照组为 (0 91± 0 16 ) ,3组比较差异均有显著性 (P值均 <0 0 5 ) ,而NSIP组与对照组比较差异无显著性。对照组只有肺泡巨噬细胞表达上述各细胞因子。结论　TGF β1、IL 8、b FGF在UIP和NSIP患者肺组织中表达强度的不同和IL 13/IFN γ的是否平衡可能参与了UIP和NSIP不同的发病过程。     

Quantitative analysis of fibroblastic foci in usual interstitial pneumonia

STUDY OBJECTIVES: Using semiquantitative scoring methods, several studies have shown that the amount of fibroblastic foci (FF), which are one of the pathologic characteristics in usual interstitial pneumonia (UIP), is a significant prognostic factor of UIP. In those studies, the degree of FF was evaluated semiquantitatively on several scales by a panel of pulmonary pathologists. However, the evaluation was somewhat subjective because interobserver variation was not small. Additionally, these methods are not entirely practical because two or more pathologists are required. In this study, we tried to develop a more quantitative scoring method of FF. PATIENTS AND METHODS: With a charge-coupled device camera, we made images of lung sections obtained from 15 patients with UIP associated with collagen vascular disease (CVD) [CVD-UIP] and 16 patients with idiopathic pulmonary fibrosis (IPF) [IPF/UIP], and calculated the proportion of FF areas in the target image areas with an image analytic software. MEASUREMENTS AND RESULTS: Our quantitative scoring method enabled us to readily and objectively evaluate the extent of FF as a quantitative percentage of FF area (%FF) score. Interobserver and intraobserver correlations were high in our method (r = 0.877 and r = 0.898, respectively). The quantitative %FF score (+/- SD) of IPF/UIP patients was 1.67 +/- 0.90%, which was significantly higher than that of CVD-UIP patients (0.39 +/- 0.24%, p < 0.0001). A Cox proportional hazards model showed that the quantitative %FF score was a significant predictor of survival in UIP patients. The quantitative %FF score had a correlation with scores assessed by the semiquantitative scoring methods previously reported, but patients with the same score assessed by the semiquantitative methods had widely varying scores assessed by our method. CONCLUSIONS: These results suggest that our quantitative scoring method for FF is more objective than the semiquantitative scoring methods previously reported, providing accurate information about the prognosis of patients with UIP.     

A retrospective analysis of distinguishing features of chest HRCT and clinical manifestation in primary Sjögren’s syndrome-related interstitial lung disease in a Chinese population

To characterize the distinctive chest high-resolution computerized tomography (HRCT) features and clinical manifestations of primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD). The demographic data, clinical manifestations, and laboratory and radiological findings of 527 pSS patients were retrospectively analyzed. ILD was defined based on the presences of pulmonary signs in HRCT. Two hundred six of 527 patients were diagnosed as pSS-ILD, and the prevalence was 39.1%. The three most frequent abnormalities in HRCT were reticular pattern (92.7%), ground-glass attenuation (87.4%), and bronchovascular bundle thickening (82%). One hundred twenty-four cases (60.2%) of the pSS-ILD patients had only a single HRCT pattern, which involved 86 non-specific interstitial pneumonitis (NSIP) cases (41.7%), 22 usual interstitial pneumonia (UIP) cases (10.68%), 8 organizing pneumonia (OP) cases (3.9%), and 8 lymphocytic interstitial pneumonia (LIP) cases (3.9%), respectively. Besides, the more important observation was that 82 cases had no less than two HRCT patterns, and NSIP admixed with OP (43.9%), NSIP admixed with UIP (35.4%), and NSIP admixed with LIP (19.5%) were the most frequent. HRCT of pSS-ILD patients demonstrated bilateral infiltrates (99%), with abnormalities predominantly in the lower lobes (89.3%) and subpleural areas (81.1%), and a few lesions were characterized by hilum distributed (8.7%). Pulmonary function tests (PFTs) revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and the rate of small airway lesions in the pSS-ILD patients was 3.5 times higher in patients of pSS. Logistic regression analysis showed that dry cough (OR 59.05), clubbing (OR 6.26), elevated lactate dehydrogenase (OR 21.38) and positive anti-Ro (OR 7.86) were relevant factors of pSS-ILD. ILD is the common pulmonary involvement of pSS and the prevalence of pSS-ILD is 39.1%. The single pattern of NSIP and UIP in HRCT are the commonest, and about 40% of the pSS-ILD patients possess multiple patterns in HRCT. The classification of idiopathic pulmonary fibrosis cannot completely include the pulmonary imaging features of pSS-ILD.     

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.