Objective To evaluate the efficacy and safety of glucocorticoids (GC) monotherapy and GC combined with tacrolimus (TAC) therapy in patients with anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD). Methods Through retrospective analysis and propensity score matching (PSM) analysis, the 2-year progression-free survival (PFS) and related side effects of ASS-ILD patients in TAC+GC group and GC monotherapy group were compared. Predictors associated with PFS were analyzed with COX. Results The 2-year PFS rate of TAC+GC group was better than that of GC group [P=0.0163; hazard ratio (HR) 0.347]; Univariate and multivariate analysis of the COX regression model for 2-year PFS in the two groups suggested that creatine kinase level (P=0.0019, HR 1.002) and initial treatment selection [(TAC+GC) vs. GC, P=0.0197, HR 0.207] were independent predictors of PFS; PSM analysis showed that the 2-year PFS rate of TAC+GC group (54.5%) was higher than that of GC group (18.2%) (P=0.0157, HR 0.275). In terms of adverse effect, there was no significant increase in GC+TAC group compared with GC group. Conclusion Compared with GC monotherapy, initial TAC+GC treatment significantly prolonged PFS in ASS-ILD patients and did not increase the incidence of drug-related complications.
Objective To evaluate the clinical relationship between serum carcinoembryonic antigen (CEA) and mortality of anti-melanoma differentiation associated gene 5 (MDA5) antibody positive dermatomyositis with interstitial lung disease (ILD). MethodsThe consecutive clinical data of 214 patients with anti MDA5 antibody positive dermatomyositis from West China Hospital of Sichuan University from February 2017 to September 2019 were collected retrospectively, including demographic, laboratory examination and imaging examination data. Patients were divided into CEA elevated group (CEA≥4.63 ng/mL) and CEA normal group (CEA<4.63 ng/mL) according to CEA level. R4.1.2 software was used for statistical analysis of all data, and Kaplan Meier method was used to draw the survival curve. Cox proportional hazard model was used to analyze the survival of patients with ILD, and to explore the risk factors associated with the survival of patients with anti-MDA5 antibody positive dermatomyositis with ILD. Results There were 180 patients with ILD who met the inclusion and exclusion criteria, 57 patients with rapidly progressive pulmonary interstitial fibrosis (RPILD), and 123 patients without RPILD; 121 women and 59 men, with an average age of 50.2±10.7 years; The average follow-up was 23.5 months, and 52 patients died. Univariable analysis suggested that CEA≥4.63 ng/mL, smoking, RPILD, lactate dehydrogenase (LDH) ≥321 IU/L, albumin<30 g/L and dyspnea were risk factors associated with death in patients with anti MDA5 dermatomyositis combined with ILD. Multivariable Cox regression analysis showed that CEA≥4.63 ng/mL [hazard ratio (HR) =3.01, 95% confidence interval (CI) 1.23 - 7.32, P=0.015], RPILD (HR=3.87, 95%CI 2.09 - 7.19, P<0.001), smoking (HR=2.37, 95%CI 1.25 - 4.47, P=0.008), LDH≥321 IU/L (HR=2.47, 95%CI 1.23 - 4.96, P=0.011), albumin<30 g/L (HR=2.57, 95%CI 1.38 - 4.78, P=0.003) were independent predictors for mortality. ConclusionsSerum CEA level can be used as a clinical prognostic predictor in patients with anti-MDA5 positive dermatomyositis and ILD. RPILD, smoking, LDH≥321 IU/L, and albumin<30 g/L are independent predictors for mortality.
Objective To explore the effects of bone marrow mesenchymal stem cells ( BMMSCs) on pulmonary fibroblasts of patients with nonspecific interstitial pneumonitis ( NSIP) , and investigate the therapeutic mechanism of BMMSCs for interstitial pulmonary fibrosis. Methods Human BMMSCs, human pulmonry fibroblasts ( HPFs) from NSIP patients, and normal HPFs were primary cultured in vitro. Then HPFs fromNSIP patients were co-cultured with BMMSCs or normal HPFs using Transwell co-culture system. After 24 hours, levels of transforming growth factor β1 (TGF-β1) and interferon inducible protein 10 ( IP-10) in culture supernatants were detected by ELISA method. Meanwhile, interleukin-6 ( IL-6) , IL-8, and monocyte chemotactic protein-1 ( MCP-1) in co-culture supernatants were detected by liquid chip. After co-cultured for 48 hours, total protein of HPFs was extracted and the expression level of alpha smooth muscle actin ( α-SMA) secreted by HPFs were detected by Western blot.Results HPFs from NSIP patients secreted higher level of IL-6, IL-8, and MCP-1 than normal HPFs, and secreted high level of α-SMA. In the Transwell co-culture system, human BMMSCs significantly reduced the levels of IL-6, IL-8, and MCP-1 secreted from HPFs of NSIP patients, and reduced the high expression of α-SMA in HPFs of NSIP patients. Conclusion Human BMMSCs can significantly reduce the secretion of IL-6, IL-8, MCP-1, and the expression of α-SMA in HPFs from NSIP patients.
Objective To investigate the lung involvement in Chinese patients with systemic sclerosis ( SSc) and its functional impact. Methods 68 patients with SSc were enrolled in Scleroderma study of PUMCH ( Peking Union Medical College Hospital) . All the patients underwent high resolution computed tomography ( HRCT) , pulmonary function testing, 6-minute walk testing, and echocardiography. And 36 patients filled in the Saint George’s Respiratory Questionnaire ( SGRQ) for assessment of healthrelated quality of life. Results HRCT revealed interstitial lung disease ( ILD) in 52 ( 76. 5% ) patients, 20 out of them without respiratory symptoms. Reticular opacification, ground-glass opacity ( GGO) , traction bronchiectasis, and honeycomb were presented respectively in 80.8% , 73.1% , 59.6% , and 30.8% of patients with SSc-ILD. Fibrosis was the predominant HRCT finding, and pure GGO ( in the absence of reticulation or architectural distortion) was only present in 8 ( 15. 7% ) patients. 57 (83.8% ) patients presented with diffusion defect, with most of them having moderate to severe impairent. Reduced FVC or TLC presented in 20 ( 29.4% ) and 28 ( 41.2% ) of patients respectively. The significant correlation was observed between the DLCO and the extent of ILD on HRCT ( rs = -0.476, P =0.000) . DLCO showed significant correlations with all the four components of the SGRQ ( Plt;0.05) . Significant correlations were also observed among the SGRQ scores and SpO2 ( maximum desaturation) or Borg index. Stepwise multiple regression analysis confirmed that the DLCO, SpO2 , and Borg index contributed to the SGRQ. Conclusions Lung involvement in Chinese SSc patients is common and insidious. The HRCT features of SSc-ILD are predominant fibrosis plus GGO, indicating little reversibility. Thus HRCT should be performed routinely in newly diagnosed SSc patients for early screening of lung involvement. The lung function defect of SSc is characterized by reduced diffusing capacity, and DLCO show better correlations with HRCT abnormities or SGRQ than FVC or TLC. Thus DLCO is of great value for early detection or severity assessment of SSc-ILD. SGRQ can be used to examine the health related quality of life of SSc patients and may reflect severity of lung involvement.
ObjectiveTo explore the expression of periostin in bronchoalveolar lavage fluid (BALF) of patients with dermatomyositis-related interstitial lung disease (DM-ILD) and rheumatoid arthritis-related interstitial lung disease (RA-ILD).MethodsA total of 44 patients with DM-ILD and 28 patients with RA-ILD were underwent bronchoalveolar lavage. Cells in BALF were collected and analyzed by absolute different cell counts. The level of periostin and Krebs von den Lungen-6 (KL-6) were tested by enzyme linked immunosorbent assay. Results of high resolution CT of patients were scored. Thirty patients without interstitial lung disease (ILD) served as a control group.ResultsLevels of periostin and KL-6 were significantly increased in BALF of patients with DM-ILD and RA-ILD compared with control group (all P<0.05). Levels of periostin were positively correlated with lymphocyte counts and levels of KL-6 in BALF (allP<0.05). Furthermore, levels of periostin were significantly correlated with high resolution CT scores (P<0.05).ConclusionsLevels of periostin are increased in patients with DM-ILD and RA-ILD. Periostin might be served as an indicator of CTD-ILD.
Objective This study aims to analyze the clinical characteristics of idiopathic inflammatory myopathy (IIM) associated interstitial lung disease (ILD) with positive anti melanoma differentiation-associated gene 5 (MDA5) antibody. Methods The clinical data of 91 patients with IIM in Shanxi Bethune Hospital from Jan 2019 to Mar 2022 were collected. Then various comparisons and analyzed retrospectively in the clinical symptoms, laboratory indicators and imaging characteristics between the negative MDA5-IIM and the positive anti-MDA5-IIM. ResultsCompared with the negative anti-MDA5-IIM patients, the significantly higher incidences of Gottron sign (71.0% vs. 38.3%), ulcerative rash (45.2% vs.16.7%), dyspnea (64.5% vs. 36.7%), and ILD (71.0% vs. 43.3%), in the positive anti-MDA5-IIM patients (P<0.05). Compared with the negative anti-MDA5-IIM patients, the more ground-glass opacification (GGO) in the positive anti-MDA5-IIM patients on high resolution computed tomography (81.8% vs.53.8%, P<0.05). Compared with the positive anti-MDA5-IIM patients without ILD, the positive anti-MDA5-IIM patients with ILD had significantly higher incidence of Gottron sign (77.3% vs. 33.3%), the increased levels of lactate dehydrogenase [(525.20±203.09) IU/L vs. (321.73±188.88) IU/L], Krebs von den Lungen-6 [(1399.55±869.64) U/mL vs. (371.56±128.92) U/mL], and D-dimer [(1226.65±902.31) U/L vs. (703.73±160.11) U/L], as well as higher positive rate of anti-Ro-52 antibody (68.2% vs. 22.2%) and the higher case fatality rate (54.5% vs. 0.0%), with all P<0.05. The triple treatment of high-dose glucocorticoid (GC) combined with intravenous cyclophosphamide (IVCY) and another immunosuppressive agent (tacrolimus or tofacitinib) was found to be effective in the MDA5-IIM associated ILD group, with a lower case fatality rate (28.6%) than high-dose GC combined with IVCY group (47.1%). Conclusions The positive anti-MDA5-IIM with ILD of patients have the higher incidence of rash and dyspnea, with GGO as the most common imaging manifestation. When rapidly progressive interstitial lung disease (RPILD) is combined, the case fatality rate higher. Meanwhile, early intensive immunosuppressive therapy may improve the survival rate of RPILD patients with positive anti-MDA5 antibody.
ObjectiveTo determine the diagnostic value of serum KL-6 level in patients with interstitial lung diseases (ILD). MethodsAll the ILD patients enrolled were hospitalized from April 2013 to April 2014. Patients with other pulmonary diseases and healthy subjects were chosen as control groups simultaneously. Serum KL-6 concentrations were measured by chemiluminescent enzyme immunoassay. The association with serum KL-6 level and pulmonary function was analyzed. ResultsThere were 149 ILD patients, 155 patients with other pulmonary diseases, and 64 healthy subjects. The average serum levels of KL-6 were (1 801.86±2 831.36) U/mL, (267.00±124.41) U/mL, (201.28±81.18) U/mL in the patients with ILD, the patients with other pulmonary diseases and the healthy controls, respectively. The sensitivity and the specificity of the serum KL-6 for the diagnosis of ILD was 83.89% and 92.24% respectively when the cut-off level was set at 500 U/mL. The Kappa value was 0.767 (P < 0.001). The best cut-off value of KL-6 was 469.5 U/mL. Serum KL-6 levels in the patients with ILD were significantly higher compared with the patients with chronic obstructive pulmonary disease, pneumonia, tuberculosis, bronchiectasis and the healthy controls, respectively (all P < 0.001). The KL-6 levels in the pulmonary alveolar proteinosis patients were significantly higher compared with the patients with cryptogenic organizing pneumonia (COP), the patients with idiopathic pulmonary fibrosis (IPF) and the patients with connective tissue disease (CTD-ILD) (all P < 0.001). While the KL-6 concentration in IPF and CTD-ILD were significantly higher than that in COP (P=0.003 and P=0.008, respectively). Significant negative correlations were found between the levels of serum KL-6 and vital capacity as a percentage of the predicted value, forced vital capacity as a percentage of the predicted value, forced expiratory volume in one second as a percentage of the predicted value and carbon monoxide diffusing capacity as a percentage of the predicted value (all P < 0.001). Follow-up study showed the levels of serum KL-6 were consistent with clinical efficacy. ConclusionSerum KL-6 level is a reliable serum marker for ILD, and is related with the severity of disease and clinical efficacy.