Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease.

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

The cryobiopsy in interstitial lung diseases guided by probe-based confocal laser endomicroscopy is feasible.

BACKGROUND: Transbronchial lung cryobiopsy (TBLB) is routinely used to diagnose the interstitial lung disease (ILD). These results are consistent with those of surgical lung biopsy. Fluoroscopy is also used to confirm the final position of the cryoprobe; however, it can increase radiation exposure for both patients and medical care personnel. Probe-based confocal laser endomicroscopy (pCLE) is a novel optical imaging technique that allows real-time imaging at the cellular level in vivo. pCLE technology can also be used to identify malignancy, acute rejection in lung transplantation, amiodarone lung, and pulmonary alveolar proteinosis and visualize elastin fibres in the alveolar compartment. OBJECTIVES: The aim of this study is to investigate the ability of pCLE to distinguish fibrotic pulmonary issues from normal lung disease and the safety and feasibility of CLE-guided bronchoscopy and transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD). METHODS: pCLE images from 17 ILD patients were obtained during TBLB. These images were then compared with histology results to assess the correspondence rate. RESULTS: pCLE imaging of the alveolar structures was performed. Key characteristics were visible, which could potentially influence the diagnostic rate (fibrotic areas) and the complication rate (blood vessel and pleura). CONCLUSION: pCLE may reduce complications and increase the diagnostic yield. It is a potential guidance tool for cryobiopsy in the patients with ILD without fluoroscopy.

The composition of the lung microbiome differs between patients with dermatomyositis and rheumatoid arthritis associated with interstitial lung disease.

Dermatomyositis and rheumatoid arthritis are inflammatory diseases that affect the skeletal muscles and joints, respectively. A common systemic complication of these diseases is interstitial lung disease (ILD), which leads to a poor prognosis and increased mortality. However, the mechanism for the initiation and development of ILD in patients with dermatomyositis is currently unknown. In the present study, we used 16S rRNA high-throughput sequencing to profile the bacterial community composition of bronchoalveolar lavage fluid of patients with dermatomyositis associated with ILD (DM-ILD; shortened to DM below), rheumatoid arthritis associated with ILD (RA-ILD; shortened to RA below) and healthy controls (N) aiming to understand the differences in their lung microbiota and to predict gene function. We found that there were more operational taxonomic units (OTUs) in the lung microbiota of both RA and DM compared to N, although there was no significant difference in the number of OTUs between RA and DM. Similarly, the diversity in alphaproteobacteria differed between RA and DM compared to N, but not between RA and DM. The lung microbiota of RA, DM and N was mainly comprised of five phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria, with 10 dominant genera. Despite the similarity in microbiota composition, we also identified 41 OTUs of lung microbiota that differed among RA, DM and N. Additionally, linear discriminant analysis effect size and linear discriminant analysis genus scores confirmed that 31 microbial biomarkers were clearly distinguished among RA, DM and N. The functional and metabolic alterations of the lung microbiota among RA, DM and N were predicted using picrust, and differentially abundant KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were identified. Research on the lung microbiota of patients with DM and RA may open new opportunities for developing biomarkers to identify high-risk patients.

Prognostic factors of patients with advanced lung cancer treated with anlotinib: a retrospective cohort study.

OBJECTIVE: Our study aimed to evaluate the main factors affecting the efficacy of anlotinib to determine the therapeutically dominant populations. METHODS: The medical records of patients with lung cancer who were treated with anlotinib from July 2018 to February 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively reviewed. The optimal cutoff prognostic nutritional index (PNI) value for predicting efficacy was determined according to receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan-Meier method and log-rank test. The prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression analyses. RESULTS: The overall disease control rate of 44 patients with lung cancer was 93.2% (41/44). The median PFS was 5.0 months (95% [confidence interval] CI: 2.2-7.8), and the median OS was 6.5 months (95% CI: 3.6-9.3). The multivariate analysis results indicated that hand-foot syndrome and high PNI values were independent protective factors of PFS and OS. CONCLUSIONS: Anlotinib was effective in treating locally advanced or advanced lung cancer. High pretreatment PNI scores and the presence of hand-foot syndrome after treatment were independent prognostic markers for favorable OS and PFS.

Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease.

BACKGROUND: Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD. METHODS: Serum samples of 30 healthy controls, 14 DM patients without ILD and 40 DM patients with ILD were collected. Serum S100A8/A9 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and levels of interleukins were measured by cytometric beads array (CBA). Then we performed multivariate logistic regression analysis to determine factors independently associated with ILD development. RESULTS: Serum IL-4, IL-6 and S100A8/A9 levels were significantly higher in DM patients with ILD than those in healthy controls (p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls (p = 0.0001). In DM patients, the levels were significantly higher in patients with A/SIP than in those with CIP (p = 0.0046, 0.0339 and 0.0133) or without ILD (p = 0.0165, 0.0370 and < 0.0001). IL-4 (r = 0.1171, p = 0.0040), IL-6 (r = 0.1174, p = 0.0040) and IL-10 (r = - 0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) (r = 0.1642, p = 0.0157) and lung function (DLCO%: r = - 0.2066, p = 0.0061, FVC%: r = - 0.2156, p = 0.0050). Moreover, logistic regression analysis revealed that S100A8/A9 levels were independently associated with ILD development in DM patients (p = 0.004). CONCLUSIONS: Serum level of S100A8/A9 may be a valuable predictor for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD.

Identification SYT13 as a novel biomarker in lung adenocarcinoma.

Synaptotagmins are a class of proteins that play an important role in the secretion of neurotransmitters by synaptic vesicles. However, recent studies have shown that members of this family also have a certain function in the development of tumors. In this study, we first identified through The Cancer Genome Atlas data analyzed that a novel synaptotagmin, SYT13, was closely related to the prognosis of lung adenocarcinoma, but was not significantly correlated with the prognosis of lung squamous cell carcinoma. Then we knocked down the expression of SYT13 gene in lung adenocarcinoma cell lines A549 and H1299, and successfully induced decreased proliferation and clonality of lung adenocarcinoma cell lines, and observed cell cycle arrest and apoptosis enhancement in both cell lines. In addition, we detected the migration ability of SYT13 knockdown lung adenocarcinoma cell lines by the cell scratch test and the transwell test. Interestingly, there was a decreased migration ability of SYT13 knockdown in H1299 cells even though there was no significant difference in the migration of A549 cells. These results demonstrate that SYT13 plays an important role in the development of lung adenocarcinoma, which deepens our understanding of the mechanism of lung adenocarcinoma development and provides new possibilities for targeted therapy of lung adenocarcinoma.

Serum S100A12 levels are correlated with clinical severity in patients with dermatomyositis-associated interstitial lung disease.

OBJECTIVE: S100A12 is an emerging inflammatory disease biomarker. Interstitial lung disease (ILD) is a common, severe complication of dermatomyositis (DM). This study was performed to investigate the association between S100A12 and disease activity and prognosis in patients with DM-associated ILD (i.e., DM-ILD). METHODS: Serum S100A12 levels were measured using enzyme-linked immunosorbent assays in patients with stable DM-ILD, patients with acute exacerbation of DM-ILD (AE DM-ILD), and healthy controls (HCs). The relationships of serum S100A12 levels with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, high-resolution computed tomography (HRCT) scores, and pulmonary functions were evaluated by multiple unpaired t-tests and Pearson correlation. RESULTS: Serum S100A12 levels were higher in patients with stable DM-ILD and those with AE DM-ILD than in HCs. Serum S100A12 levels in patients with stable DM-ILD and those with AE DM-ILD were positively correlated with CRP, ESR, and ferritin. S100A12 levels were positively correlated with HRCT scores in patients with stable DM-ILD and those with AE DM-ILD, while they were negatively correlated with predicted percentages of forced vital capacity and predicted percentages of carbon monoxide diffusing capacity in those patients. CONCLUSION: Our findings demonstrate the usefulness of serum S100A12 levels for assessing clinical severity and prognosis of DM-ILD.