Lung microbiome and cytokine profiles in different disease states of COPD: a cohort study.

Increasing evidence indicates that respiratory tract microecological disorders may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Understanding the composition of the respiratory microbiome in COPD and its relevance to respiratory immunity will help develop microbiome-based diagnostic and therapeutic approaches. One hundred longitudinal sputum samples from 35 subjects with acute exacerbation of COPD (AECOPD) were analysed for respiratory bacterial microbiome using 16S ribosomal RNA amplicon sequencing technology, and the sputum supernatant was analysed for 12 cytokines using a Luminex liquid suspension chip. Unsupervised hierarchical clustering was employed to evaluate the existence of distinct microbial clusters. In AECOPD, the respiratory microbial diversity decreased, and the community composition changed significantly. The abundances of Haemophilus, Moraxella, Klebsiella, and Pseudomonas increased significantly. Significant positive correlations between the abundance of Pseudomonas and TNF-α, abundance of Klebsiella and the percentage of eosinophils were observed. Furthermore, COPD can be divided into four clusters based on the respiratory microbiome. AECOPD-related cluster was characterized by the enrichment of Pseudomonas and Haemophilus and a high level of TNF-α. Lactobacillus and Veillonella are enriched in therapy-related phenotypes and may play potential probiotic roles. There are two inflammatory endotypes in the stable state: Gemella is associated with the Th2 inflammatory endotypes, whereas Prevotella is associated with the Th17 inflammatory endotypes. Nevertheless, no differences in clinical manifestations were found between these two endotypes. The sputum microbiome is associated with the disease status of COPD, allowing us to distinguish different inflammatory endotypes. Targeted anti-inflammatory and anti-infective therapies may improve the long-term prognosis of COPD.

MiR-144-3p inhibits the proliferation and metastasis of lung cancer A549 cells via targeting HGF.

AIM: MicroRNAs have been confirmed as vital regulators in gene expression, which could affect multiple cancer cell biological behaviors. This study aims to elucidate the molecular mechanism of miR-144-3p in lung cancer cellular proliferation and metastasis. METHODS: MiR-144-3p expression in lung cancer tissues and cell lines was detected by qRT-PCR. HGF was predicted as the target gene of miR-144-3p using TargetScan and dual luciferase reporter assay. Immunohistochemistry and qRT-PCR were used to explore the impacts of HCF on lung cancer tissues and cell lines. Impacts of miR-144-3p and HGF on cancer cellular proliferation, migration and invasion were elucidated by CCK-8, Flow cytometry, Transwell invasion and Wound-healing assay. Moreover, nude mouse xenograft model was established to evaluate the effects of miR-144-3p on lung cancer cells. RESULTS: MiR-144-3p exhibited a reduction in both lung cancer tissues and cell lines. HGF was a direct target of miR-144-3p. In contrast to the miR-144-3p expression level, HGF showed a higher level in lung cancer tissues and cell lines. Overexpression miR-144-3p suppressed A549 and NCI-H1299 cell proliferation and metastasis, whereas this was reversed by HGF. MiR-144-3p exhibited an inhibitory effect on A549 cell-induced tumor growth of nude mice. CONCLUSIONS: This study reveals miR-144-3p/HGF axis may be involved in the suppression of lung cancer cellular proliferation and development, and miR-144-3p may function as a potential therapeutic target in lung cancer treatment in the future.

Associations Between Sputum Torque Teno Virus Load and Lung Function and Disease Severity in Patients With Chronic Obstructive Pulmonary Disease.

Purpose: Viral load of Torque Teno virus (TTV) is elevated in immunosuppressed patients. The weakened immune response is typical in chronic obstructive pulmonary disease (COPD) patients. However, the relationship between TTV and COPD is still unknown. Patients and Methods: We enrolled 91 patients admitted to hospitals with acute exacerbation of COPD (AECOPD) between January 2017 and August 2017 (ClinicalTrials.gov ID, NCT03236480). Sputum samples were gathered during hospitalization and the 120-day follow-up. TTV distribution and genogroups were assessed, and the associations between viral loads and clinical parameters were analyzed. Results: TTV DNA was detected in 95.6% of COPD patients, and the viral load was nearly invariable at the stable and exacerbation states. Most TTV DNA-positive patients carried four distinct genotypes. Sputum load of TTV was positively associated with RV/TLC (r = 0.378, p = 0.030), and negatively correlated with FEV1/pre and FEV1/FVC (r = -0.484, -0.432, p = 0.011, 0.024, respectively). Neutral correlation between the TTV DNA load and COPD assessment test (CAT) scores (r = 0.258, p = 0.018) was observed. Conclusion: Sputum loads of TTV DNA could be a novel indicator for lung function and disease severity assessment in COPD patients.

Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients.

Background: T helper (Th) cell cytokine imbalances have been associated with the pathophysiology of chronic obstructive pulmonary disease (COPD), including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Clarifying cytokine profiles during COPD acute exacerbation (AE) and their relationships with clinical manifestations would help in understanding the pathogenesis of disease and improve clinical management. Materials and Methods: Eighty seven patients admitted to the hospital with AEs of COPD were included in this study, and follow-up was conducted after discharge (every 30 days, for a total of 120 days). Sputum samples of patients at different time points (including at admission, discharge, and follow-up) were collected, and sputum cytokine profiling (12 cytokines in total) was performed using a Luminex assay. Results: According to the cytokine profiles at admission, patients were divided into three clusters by a k-means clustering algorithm, namely, Th1high Th17high (n=26), Th1lowTh17low (n=56), and Th1high Th17low (n=5), which revealed distinct clinical characteristics. Patients with Th1high Th17low profile had a significantly longer length of non-invasive ventilation time and length of hospital stay than patients with Th1high Th17high profile (7 vs 0 days, 22 vs 11 days, respectively, p < 0.05), and had the highest AE frequency. Sputum levels of Th17 cytokines (IL-17A, IL-22, and IL-23) during AE were negatively correlated with AE frequency in the last 12 months (r = -0.258, -0.289 and -0.216, respectively, p < 0.05). Moreover, decreased sputum IL-17A levels were independently associated with increased AE frequency, with an OR (95% CI) of 0.975 (0.958-0.993) and p = 0.006. Conclusion: Th1/Th17 imbalance during AE is associated with the severity of COPD. Decreased Th17 cytokine expression is correlated with increased AE frequency. The Th1/Th17 balance may be a specific target for the therapeutic manipulation of COPD.

The value of apolipoprotein E in distinguishing benign and malignant unilateral pleural effusions.

Pleural effusion (PE) remains insurmountable challenge and public health problem, requiring novel noninvasive biomarkers for accurate diagnosis. The aim of this study was to assess the clinical significance of apolipoprotein E (Apo-E) in PE, in order to determine its potential use as a diagnostic biomarker for malignant PE (MPE).PE samples were obtained from 127 patients and the etiology of PE was determined by multiple diagnostic techniques. Apo-E levels were then measured in the pleural fluid samples.58 PE patients were diagnosed with tumors, while 69 were tumor-free. Apo-E levels in MPE patients were significantly higher than those with benign PE (BPE) (P < .05). An Apo-E cut-off of 69.96 ng/mL yielded sensitivity and specificity of 79.31% and 73.91% respectively for MPE detection. The area under the curve for Apo-E was 0.793 (95% confidence interval: 0.712 to 0.860), which was smaller than that of carcinoembryonic antigen (CEA) (Z = 2.081, P<.05). In addition, the combination of Apo-E and CEA detection yielded a higher sensitivity of 87.90% and specificity of 95.65% in diagnosing MPE.In conclusion, Apo-E levels in PE may be a potential biomarker for the detection of MPE. The combined detection of Apo-E and CEA could improve the diagnostic sensitivity and specificity for MPE. These findings provide a simple and convenient method for clinical screening and detection of PE.