Blood purification in two patients with clinically amyopathic dermatomyositis associated with interstitial lung disease with anti-melanoma differentiation-associated gene-5 antibody (MDA-5).

Patients of clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia (CADM-RFIP) with positive anti-MDA5 antibody usually presents rapid deterioration and traditional therapy such as cyclophosphamide combined with high-dose prednisone pulse therapy shows no clear benefit at whiles. However, blood purification combined with traditional therapy works according to the literature. We herein report two CADM-RFIP patients administered with DNA immunoadsorption combined with traditional therapy and then reviewed the literature of blood purification in CADM-RFIP patients at home and abroad to date. We emphasize blood purification such as DNA immunoadsorption could apply in the early stage of CADM-RFIP, which can decrease inflammation and allow us more time to control the condition better.

Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

The present study was aimed at exploring the protective effects of Salvianolic acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic injuries were induced in mice by a single intragastrical administration of 300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB, 100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, pro-inflammatory cytokine release, and oxidative stress damages in lung tissues and mortality of mice were attenuated by SalB in a dose-dependent manner. Furthermore, SalB was noted to enhance the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also inhibited the increasing expression of transforming growth factor (TGF)-ß1 and the phosphorylation of its downstream target Smad3 which were enhanced by PQ. These results suggest that SalB may exert protective effects against PQ-induced lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of Nrf2/Nox4 redox balance and TGF-ß1/Smad3 signaling.

Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease.

Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud's disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.

[The correlation of helper T lymphocyte 1/helper T lymphocyte 2 with clinical and image features in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To identify whether the helper T lymphocyte 1 (Th1)/helper T lymphocyte 2 (Th2) of patients' serum and bronchoalveolar lavage fluid (BALF) at admission could represent the severity of idiopathic pulmonary fibrosis (IPF) and whether its change at six months could predict the progression of the disease. METHODS: Eighty-three patients with IPF were subjected to pulmonary function tests (PFTs), dyspnea scores, arterial blood gas analysis, six-minute walk test (6MWT) and high-resolution computed tomography (HRCT). The serum and BALF specimen of these patients were obtained as well as 20 control serum and 10 control BALF specimen. A total of 55 patients were followed up, and their BALF and serum levels of interferon γ(IFNγ) and IL-4 were detected by enzyme-linked immunoadsorbent assay (ELISA). The correlation between the IFNγ/IL-4 levels (at admission and the change of that at six months follow-up) and the clinical, physiological and image features in the IPF patients were analyzed. RESULTS: The baseline serum and BALF level of IFNγ/IL-4 (0.8 ± 0.3) in the IPF patients was lower than that in the control group (1.4 ± 0.2), which showed significant correlation with the course of disease, dyspnea scores, FEV1%, FVC%, TLC%, maximum desaturation, 6MWD and CT-fib (all P values<0.05). The serum level of IFNγ/IL-4 showed positive correlation with CT-alv (r = 0.340, P<0.01). During follow-up, no statistic difference was found in the serum levels of IFNγ, IL-4 and IFNγ/IL-4 between the IPF patients with or without glucocorticoids treatment. There were significant aggravation in the dyspnea scores, FEV1%, FVC%, CT-alv, CT-fib, IFNγ and IL-4 at six months follow-up. Significant correlation had been showed between the change of the serum IFNγ/IL-4 level with the changes of the dyspnea scores, FVC%, TLC%, DLCO%, 6MWD and CT-fib in the IPF patients (P < 0.05). CONCLUSIONS: There are disequilibrium of the Th1/Th2 in the serum and the BALF of the IPF patients. The Th1/Th2 level could represent severity of the disease, and the serum level change of Th1/Th2 in the follow-up could predict the progression of the diseases in the IPF patients.

[Screening of potential proteins from patients with idiopathic pulmonary fibrosis by using of surface enhanced laser desorption/ionization time of flight mass spectrum].

OBJECTIVE: To screen potential proteins in bronchoalveolar lavage fluid (BALF) and serum samples obtained from patients with idiopathic pulmonary fibrosis (IPF), for the purpose of discovering candidate biomarkers. METHODS: BALF and serum samples from 34 patients diagnosed IPF (IPF group) and 25 non-smoker healthy controls (control group) were collected. Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) was used to obtain protein fingerprints from BALF and serum samples. Biomarker Wizard and Biomarker Pattern were introduced in bioinformatics analysis. RESULTS: A total of 247 protein peaks were detected in BALF, and 13 peaks with statistical difference compared with control group. Among 13 detected protein peaks, 7 with mass/charge ratio (M/Z) values of 2240.57, 3459.32, 3501.78, 4146.50, 4516.51, 4615.88, 5651.26 were statistically up-regulated (all P < 0.01); and 6 peaks with M/Z values of 4989.91, 5043.68, 6968.76, 11 687.70, 11 782.10, 14 733.30 were significantly down-regulated (all P < 0.01). In addition, 142 protein peaks were differentially expressed in serum samples, and 9 peaks with statistical differences. Among them, 9 peaks with M/Z values of 3382.59, 3453.39, 4608.28, 5825.48, 8936.76, 9164.27, 11 525.30, 11 689.40 and 11 886.00 were significantly up-regulated (P < 0.05 or P < 0.01), compared with control group. CONCLUSIONS: The present work demonstrated that SELDI-TOF-MS technology be capable of detecting differentially expressed protein peaks in BALF and serum samples from IPF patients. Further investigations were guaranteed to elucidate their potential diagnostic value in clinical practice.

[Effect of corticosteroids upon the prognosis of idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the therapeutic effect of corticosteroids upon idiopathic pulmonary fibrosis (IPF) and the impact of corticosteroids upon survival time. METHODS: Clinical data of 94 corticosteroid treatment and 32 non-corticosteroid treatment IPF patients during 2000 - 2004 were retrospectively analyzed and their survival rates compared between two groups. The corticosteroid treatment patients were divided into 3 groups: improved, steady and worsened group according to the pulmonary function data. Therapeutic effects and survival rates were compared between these 3 groups. RESULTS: In the treatment group, 6 (6.4%) patients could not be located, 22 (23.4%) patients survived, and 66 (70.2%) patients died. In the non-corticosteroid treatment group, 1 (3.1%) patients could not be located, 2 (6.3%) patients survived and 29 (90.6%) patients died. No statistically significant difference existed between the two groups (P > 0.05). Sixty-two corticosteroid treatment patients were followed up for 3-6 months. Among them, 19 (30.7%) patients improved, 11 (17.7%) patients remained steady and 32 (51.6%) patients worsened in pulmonary function. In 19 improved patients, 7 (36.8%) survived and 12 (63.2%) died. In 11 steady patients, 3 (27.2%) survived and 8 (72.7%) died. In 32 worsened patients, 3 (9.4%) could not be located, 1(3.1%) survived and 28 (87.5%) died. The survival rate of the improved and steady groups was higher than that of the worsened group (P < 0.01). CONCLUSIONS: There is some therapeutic effect of corticosteroids in the early alveolitis stage of IPF. The prognosis of the patients with improved and steady pulmonary function parameters during the first 3 - 6 months is better than that of worsened patients.

[A retrospective cohort study of prognostic factors for death in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the prognostic implications of clinical, radiographic, and physiological variables in idiopathic pulmonary fibrosis (IPF). METHODS: The clinical, pulmonary physiological, bronchoalveolar lavage fluid (BALF) cell differentials and lung high-resolution computed tomography (HRCT) at diagnosis in 126 patients with IPF were retrospectively analyzed. Univariate and multivariate Cox proportional-hazards regression analysis was used to evaluate various parameters associated with hazard ratio (HR). The survival rates of all groups were compared using the Kaplan-Meier method. RESULTS: In 29.6 months of average follow-up time, the survival rate of the IPF patients was 46.8% (59/126), and the median survival time was 30 months after diagnosis. Glucocorticoids and/or cytotoxic drugs for patients with IPF did not change the prognosis. The survival rates between groups by gender and smoking status showed no statistically significant difference (Ward: 0.11, 1.65, P>0.05). The patients were divided into 2 groups by the median (the cutoff point value) of significant variables in univariate Cox proportional-hazards regression analysis, and the survival rates showed statistically significant difference by dyspnea scale, FVC%, TLC%, DLCO%, neutrophil percentage and eosinophil percentage in BALF, and the reticular and honeycomb lung score (Logrank: 13.52-57.52, P<0.05). The results of multivariate Cox proportional-hazards regression analysis showed that TLC%, DLCO%, HRCT reticular score and honeycomb lung score were factors that affected the prognosis of patients with IPF (Wald=5.76-21.48, P<0.05). CONCLUSIONS: TLC%, DLCO%, cell differentials of BALF and the degree of pulmonary fibrosis were the main factors affecting the prognosis of patients with IPF. TLC% and DLCO% showed a negative correlation with the prognosis of patients with IPF. Glucocorticoids and/or cytotoxic drug therapy had no effect on the prognosis of patients with IPF.

[Cell profiles of bronchoalveolar lavage fluid as prognostic indicators of idiopathic pulmonary fibrosis].

OBJECTIVE: To determine whether clinical and physiologic variables and bronchoalveolar lavage fluid (BALF) cell profiles affect the survival of patients with idiopathic pulmonary fibrosis (IPF). METHODS: There were 43 patients with clinically diagnosed IPF in the study. The Kaplan-Meier method and the Log-rank test were used to estimate the survival in the two groups and Cox proportional hazard regression was used to evaluate the Hazard Ratio in the IPF patients. RESULTS: The IPF patients presented with restrictive ventilatory disorders [FVC%: (61 +/- 18)%, TLC%: (54 +/- 13)%] and gas exchange impairment [D(L)CO%: (48 +/- 14)%]. The mean follow-up time was 30.7 months, and the median survival of IPF patients was 28.5 months after diagnosis. FVC ( Wald = 6.71, P < 0.01), TLC ( Wald = 12.37, P < 0.01) , D(L)CO ( Wald = 22.78, P < 0.01), neutrophil ( Wald = 16.26, P < 0.01) and eosinophil ( Wald = 7.73, P < 0.01) percentages were prognostic variables in the univariate Cox proportional hazard regression, and only D(L)CO (HR = 0.93, Wald = 15.77, P < 0.01) and the neutrophil percentage (HR = 1.07, Wald = 6.83, P < 0.01) were prognostic variables for IPF patients in the multivariate Cox proportional hazard regression. CONCLUSIONS: The IPF patients were predominantly old males and presented with restrictive ventilatory disorders and gas exchange impairment. Glucocorticoids and/or cytotoxic drugs could not improve the prognosis for the IPF patients. DLCO and BALF neutrophil percentage were prognostic variables, and DLCO was negatively correlated with the prognosis while the neutrophil percentage was positively correlated with the prognosis in the IPF patients.