Biogeography of the Respiratory Tract Microbiome in Patients With Malignant Tracheal Tumors.

BACKGROUND: This study aimed to characterize the bacterial microbiota in the oral cavity (OC), throat, trachea, and distal alveoli of patients with primary malignant tracheal tumors (PMTT), including squamous cell carcinoma (SCC) and salivary gland carcinoma patients (SGC), for comparison with a matched non-malignant tracheal tumor (NMTT) group. METHODS: Patients with pathological diagnosis of PMTT and NMTT were included in this study. Saliva, throat swab (TS), trachea protected specimen brush (PSB), and bronchoalveolar lavage fluid (BALF) samples were collected for 16S rRNA gene sequencing. The composition, diversity, and distribution of the microbiota were compared among biogeographic sampling sites and patient groups. The relationship between the genera-level taxon abundance and tracheal tumor types was also investigated to screen for candidate biomarkers. FINDINGS: The most represented phyla in the four sites were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In SCC patients, the relative abundance of Bacteroidetes and Firmicutes gradually decreased with increasing depth into the respiratory tract, while the relative abundance of Proteobacteria gradually increased. Bacterial communities at the four biogeographic sites formed two distinct clusters, with OC and TS samples comprising one cluster and PSB and BALF samples comprising the other group. Principal coordinate analysis showed that trachea microbiota in SCC patients were distinct from that of SGC or NMTT patients. In the trachea, AUCs generated by Prevotella and Alloprevotella showed that the abundance of these genera could distinguish SCC patients from both NMTT and SGC patients. INTERPRETATION: The structure of respiratory tract microbiota in PMTT patients is related to tumor type. Certain bacteria could potentially serve as markers of SCC, although verification with large-sample studies is necessary.

Effects of exogenous probiotics on the gut microbiota and clinical outcomes in critically ill patients: a randomized controlled trial.

BACKGROUND: Gut microbiota play an important role in the inflammation. This study aimed to investigate whether exogenous probiotics could improve the intestinal barrier function effect via attenuating inflammation and immunomodulation to improve the clinical outcomes in critically ill patients. METHODS: A single-blind, randomized controlled trial was performed in a respiratory intensive care unit (RICUs). Patients assigned to the intervention group received probiotics Clostridium butyricum until death or discharge. Stool and blood samples were collected on the 1st day and 15th day of administration. Primary clinical outcomes and clinical manifestations were recorded during the follow-up period. RESULTS: There were 61 patients in this study, with 28 patients receiving probiotics. There were no differences in the mortality and hospital stay between intervention group and control group. In addition, the duration of fever (% of hospital stays) was significantly shorter in the intervention group as compared to control group (4.85% vs. 12.94%, P=0.00). The incidence of constipation significantly reduced in the intervention group (17.86% vs. 42.42%, P=0.04). The overall ratio of gastrointestinal adverse effects was comparable between them. Bactericides significantly decreased after probiotic intervention (Δm=-0.69, P=0.048), while Escherichia coli and Enterococcus tended to decrease in the intervention group (Δm=-0.65, P=0.08; Δm=-0.52, P=0.22) on the day 15. No fluctuation was observed in the Bifidobacterium and Lactobacillus after probiotic intervention. CONCLUSIONS: Our study fails to show the beneficial effects of probiotics on the primary clinical outcomes in critically ill patients. The intestinal barrier is damaged, and probiotics may reduce the burden of Gm-bacteria from the gut.

Differences in the Clinical Characteristics of Early- and Late-Onset Asthma in Elderly Patients.

Differences between early-onset and late-onset asthma in elderly subjects have not been comprehensively described in China. We conducted a cross-sectional study to determine the phenotypic differences between early-onset asthma (EOA) and late-onset asthma (LOA) in elderly patients. We collected clinical and physiological data from 176 elderly patients with asthma. Participants were divided into two groups: EOA group and LOA group. Demographics, comorbidities, inflammatory parameters, lung function, severity, asthma control, and medication use among EOA and LOA elderly patients were compared. Elderly subjects with EOA had more atopic disease, a stronger positive family history of asthma, higher IgE, and exhaled nitric oxide levels as compared to those with LOA. In contrast, elderly subjects with LOA had lower lung function and more marked fixed airflow obstruction (FAO). Elderly subjects with LOA had a higher incidence of chronic obstructive pulmonary disease (COPD). No differences were observed in age, gender, BMI, history of smoking, severity, and asthma control between the two groups. Both similarities and differences exist between elderly subjects with EOA and those with LOA in China. Further work is required to determine the pathophysiological, clinical, and therapeutic implications for different asthma phenotypes in elderly subjects.

Protective effect of exogenous hydrogen sulfide on pulmonary artery endothelial cells by suppressing endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder characterized by inflammation, representing a significant leading cause of chronic morbidity and mortality. Reports have implicated hydrogen sulfide (H2S) in both the pathology and treatment of COPD. The present study aimed to explore the effects involved with exogenous H2S on endoplasmic reticulum stress (ERS) and pulmonary artery endothelial cells (PAECs) in a rat model of COPD. METHODS: Rat models of COPD were successfully established by means of passive smoke exposure and intratracheal injection with lipopolysaccharide (LPS). Pulmonary function tests were performed and histopathological changes were observed. The expression of ERS markers, glucose-regulated protein-78 (GRP78), and C/EBP homologous protein (CHOP) and caspase-12, associated with ERS-induced apoptosis, were determined by western blot and immunohistochemistry methods. TUNEL assay was applied to determine the apoptosis index (AI) in PAECs. RESULTS: Treatment with NaHS was followed by the exhibition of markedly increased forced expiratory volume over 0.3 s (FEV0.3)/forced vital capacity (FVC) and dynamic lung compliance as well as integral optical density (IOD), with decreased RI among COPD rats. Western blot analysis, immunohistochemistry and TUNEL assay results revealed there to be reduced expressions of GRP78, CHOP and caspase-12 in the lung tissues and AI of PAECs, post NaHS treatment. CONCLUSION: The key findings of the current study highlight ERS in COPD rats, as well as well as reduced apoptosis in PAECs in connection with exogenous H2S by suppressing ERS.

Effectiveness of meditative movement on COPD: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of meditative movement (tai chi, yoga, and qigong) on COPD remained unclear. We undertook a systematic review and meta-analysis to determine the effectiveness of meditative movement on COPD patients. METHODS: We searched PubMed, Web of Science, EMBASE, and the Cochrane Center Register of Controlled Trials for relevant studies. The methods of standard meta-analysis were utilized for identifying relevant researches (until August 2017), quality appraisal, and synthesis. The primary outcomes were the 6-minute walking distance (6MWD), lung function, and dyspnea levels. RESULTS: Sixteen studies involving 1,176 COPD patients were included. When comparing with the control group, the 6MWD was significantly enhanced in the treatment group (3 months: mean difference [MD]=25.40 m, 95% CI: 16.25 to 34.54; 6 months: MD=35.75 m, 95% CI: 22.23 to 49.27), as well as functions on forced expiratory volume in 1 s (FEV1) (3 months: MD=0.1L, 95% CI: 0.02 to 0.18; 6 months: MD=0.18L, 95% CI: 0.1 to 0.26), and FEV1 % predicted (3 months: 4L, 95% CI: 2.7 to 5.31; 6 months: MD=4.8L, 95% CI: 2.56 to 7.07). Quality of life for the group doing meditative movement was better than the control group based on the Chronic Respiratory Disease Questionnaire dyspnea score (MD=0.9 units, 95% CI: 0.51 to 1.29) and fatigue score (MD=0.75 units, 95% CI: 0.42 to 1.09) and the total score (MD=1.92 units, 95% CI: 0.54 to 3.31). CONCLUSION: Meditative movement may have the potential to enhance lung function and physical activity in COPD patients. More large-scale, well-designed, multicenter, randomized controlled trials should be launched to evaluate the long-range effects of meditative movement.

Detection and analysis of apoptosis- and autophagy-related miRNAs of mouse vascular endothelial cells in chronic intermittent hypoxia model.

Endothelial dysfunction is the main pathogenic mechanism of cardiovascular complications induced by obstructive sleep apnea/hyponea syndrome (OSAHS). Chronic intermittent hypoxia (CIH) is the primary factor of OSAHS-associated endothelial dysfunction. The hypoxia inducible factor (HIF) pathway regulates the expression of downstream target genes and mediates cell apoptosis caused by CIH-induced endothelial injury. miRNAs play extensive and important negative regulatory roles in this process at the post-transcriptional level. However, the regulatory mechanism of miRNAs in CIH tissue models remains unclear. The present study established a mouse aortic endothelial cell model of CIH in an attempt to screen out specific miRNAs by using miRNA chip analysis. It was found that 14 miRNAs were differentially expressed. Of them, 6 were significantly different and verified by quantitative real-time PCR (Q-PCR), of which four were up-regulated and two were down-regulated markedly. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, we established signaling networks by GO to predict the target genes of the 6 miRNAs. It was found that the 6 identified miRNAs were apoptosis- or autophagy-related target genes. Down-regulation of miR-193 inhibits CIH induced endothelial injury and apoptosis- or autophagy-related protein expression. In conclusion, our results showed that CIH could induce differential expression of miRNAs, and alteration in the miRNA expression pattern was associated with the expression of apoptosis- or autophagy-related genes.

Inhibition of microRNA-218 reduces HIF-1α by targeting on Robo1 in mice aortic endothelial cells under intermittent hypoxia.

OBJECTIVE: To investigate the effects of miR-218 on expression of hypoxia-inducible factors 1α (HIF-1α), vascular endothelial growth factor (VEGF) and cell apoptosis in normal mice aortic endothelial cells under intermittent hypoxia (IH) condition. METHODS: Anti-miR-218 inhibitor, miR-negative control and miR-218 mimic were used to tranfect the cells in different groups under IH condition. Both RT-PCR and Western blot were used to determine the expressions of HIF-1α and VEGF. Akt, p-Akt and cell apoptosis related proteins bcl-2, bax and caspase-3 and roundabout 1 (Robo1) were measured using Western blot. Cell apoptosis was evaluated by flow cytometry. Statistical analysis was performed using SPSS 18.0. RESULTS: Expression of miR-218 was significantly up-regulated in the IH group and was significantly inhibited when cells were transfected with miR-218 inhibitor. Down regulation of miR-218 could reduce the expression of HIF-1α and VEGF under intermittent hypoxia condition. In cells transfected with miR-218 mimic, expression of HIF-1α and VEGF significantly increased compared with the control. However, when treated with LY294002, the expression of HIF-1α and VEGF both decreased. Apoptosis assay showed that down regulation of miR-218 could inhibit intermittent hypoxia induced cell apoptosis, decrease expression of caspase-3 and bax and increase expression of bcl-2 under intermittent hypoxia condition. At last, silencing Robo1 could significantly enhance the expression of HIF-1α under IH condition. CONCLUSION: Inhibition of miR-218 could reduce the expression of HIF-1α and protect against IH-induced apoptosis in mice aortic endothelial cells. The effects were associated with PI3K/AKT pathway and might through targeting of Robo1.

Does high-flow nasal cannula oxygen improve outcome in acute hypoxemic respiratory failure? A systematic review and meta-analysis.

INTRODUCTION: To evaluate the efficacy of high-flow nasal cannula (HFNC) in the rate of intubation and mortality for patients with acute hypoxemic respiratory failure. METHODS: We searched Pubmed, EMBASE, and the Cochrane Library for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the rate of intubation; secondary outcome was mortality in the hospital. Study-level data were pooled using a random-effects model when I2 was >50% or a fixed-effects model when I2 was <50%. RESULTS: Eight randomized controlled studies with a total of 1,818patients were considered. Pooled analysis showed that no statistically significant difference was found between groups regarding the rate of intubation (odds ratio [OR] = 0.79; 95% confidence interval [CI]: 0.60-1.04; P = 0.09; I2 = 36%) and no statistically significant difference was found between groups regarding hospital mortality (OR = 0.89; 95% CI: 0.62-127; P = 0.51; I2 = 47%). CONCLUSIONS: The use of HFNC showed a trend toward reduction in the intubation rate, which did not meet statistical significance, in patients with acute respiratory failure compared with conventional oxygen therapy (COT) and noninvasive ventilation (NIV). Moreover no difference in mortality. So, Large, well-designed, randomized, multi-center trials are needed to confirm the effects of HFNC in acute hypoxemic respiratory failure patients.

WITHDRAWN: Detection and analysis of apoptosis- and autophagy-related miRNAs of vascular endothelial cells in a mouse chronic intermittent hypoxia model.

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Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis and COPD: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (AECOPD). METHODS: We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was clinical success at early follow-up. Study-level data were pooled using a random-effects model when I(2) was >50% or a fixed-effects model when I(2) was <50%. RESULTS: Eleven randomized controlled studies were considered. There was no difference between moxifloxacin and comparator agents with regard to treatment success in intention-to-treat (ITT) [odds ratio (OR) =1.18, 95% confidence interval (CI) 0.98-1.42], clinically evaluable (CE) (OR 1.13, 95% CI, 0.93-1.37) patients, or adverse effects in general (OR 1.00, 95% CI, 0.86-1.17). Moxifloxacin was associated with better microbiological success (OR 1.45; 95% CI, 1.14-1.85). CONCLUSIONS: Moxifloxacin was as clinically equivalent and bacteriologically superior to the antibiotic regimens routinely used in patients with AECB and AECOPD. Moxifloxacin therapy may be a promising and safe alternative to empirical treatment for AECB and AECOPD.

Obstructive sleep apnea syndrome is associated with metabolic syndrome and inflammation.

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular morbidity and mortality. However, the underlying mechanism is unclear. In this cross-sectional study, we investigated the influence of OSA on metabolic syndrome (MetS) and inflammation, which were considered as cardiovascular risks. A total of 144 consecutive male patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for glucose, high-sensitivity C-reactive protein (hs-CRP) and lipids measurement. A metabolic score was established as the total number of the positive diagnostic criteria of metabolic syndrome for each patient. Systolic blood pressure, diastolic blood pressure, fasting glucose, hs-CRP and metabolic score significantly increased with the aggravation of OSA severity. Metabolic score increased from 1.74 ± 1.20 to 2.89 ± 0.99 with OSA severity (p = 0.000). hs-CRP increased from 0.68 (0.43-1.10) to 1.44 (0.62-4.02) mg/L with OSA severity (p = 0.002). After adjustment for confounders, apnea-hypopnea index and body mass index (BMI) were the major contributing factors for metabolic score (ß = 0.257, p = 0.003 and ß = 0.344, p = 0.000, respectively), lowest O2 saturation and BMI were the independent predictors of hs-CRP (ß = -0.255, p = 0.003 and ß = 0.295, p = 0.001, respectively). OSA is independently associated with sum of metabolic components and hs-CRP.

Probiotics for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of high-quality randomized controlled trials.

BACKGROUND: Ventilator-associated pneumonia (VAP) is considered to be a worldwide issue along with the development of supportive ventilation. The preventing strategy is of great importance for its poor prognostic and difficulties in treatment. Probiotics have been advocated as one of the possible preventive measures. We conducted a systematic review and meta-analysis to explore the potential benefits of probiotics. METHODS: The databases, Web of science, PubMed, Ovid and Cochrane lib were searched for randomized controlled trials (RCTs) publications that compared the effectiveness of probiotics with placebo in the prevention of VAP. The incidence of VAP was considered as the primary endpoint, mortality, length of stay in intensive care units (ICUs), etiology of the infections were considered as secondary endpoints. RESULTS: A total of 844 patients from 5 trials were subjected to meta-analysis. Probiotics did not significantly decrease the incidence of VAP (RR 0.94, 95%CI 0.85-1.04, p=0.22), however, the administration of probiotics reduced the risk of VAP caused by Pseudomonas aeruginosa (P. aeruginosa) (RR 0.30, 95%CI 0.11-0.91, P=0.03). It failed to affect any other endpoints. CONCLUSION: Probiotic prophylaxis of ventilator-associated pneumonia remained inconclusive and it failed to improve the prognosis of general mechanically ventilated patients. It was noteworthy that infections caused by P. aeruginosa was reduced by administration of probiotics. In further, it is recommended that advanced studies should exploit transformation in pathogenic microorganisms owing to administration of probiotics as well as the specific population.

The changes induced by cyclophosphamide in intestinal barrier and microflora in mice.

Infection is one of the most commonly encountered complication during chemotherapy treatment, and recent studies showed that such infections are aroused primarily from the intestinal microflora through bacterial translocation. We aimed to investigate the alterations of mucosal barrier and colonization resistance in mouse treated with cyclophosphamide (CTX) to further understand the translocation mechanism. Male Balb/c mice were administered intraperitoneally with CTX at 25 mg/kg, 50 mg/kg and 100 mg/kg for 5 days. We found that pretreatment with CTX, especially at high dose, increased the potentially pathogenic bacteria counts (Escherichia coli, enterobacteraceae, Pseudomonas and enterococci) and the intestinal permeability, which was associated with the reduction of tight junctions and adherens junctions. Our results suggested that disruption of mucosal barrier and colonization resistance may be partly responsible for the bacterial translocation during chemotherapy. Thus, modulation of mechanical mucosal barrier and colonization resistance might represent a new opportunity for applications in cancer patients to reduce infectious complications.

Probiotics' effects on the incidence of nosocomial pneumonia in critically ill patients: a systematic review and meta-analysis.

INTRODUCTION: To evaluate the efficacy of probiotics in preventing nosocomial pneumonia in critically ill patients. METHODS: We searched PubMed, EMBASE, and the Web of Science for relevant studies. Two reviewers extracted data and reviewed the quality of the studies independently. The primary outcome was the incidence of nosocomial pneumonia. Study-level data were pooled using a random-effects model when I(2) was > 50% or a fixed-effects model when I(2) was < 50%. RESULTS: Twelve randomized controlled studies with a total of 1,546 patients were considered. Pooled analysis showed a statistically significant reduction in nosocomial pneumonia rates due to probiotics (odd ratio [OR]= 0.75, 95% CI 0.57 to 0.97, P = 0.03, I(2) = 46%). However, no statistically significant difference was found between groups regarding in-hospital mortality (OR = 0.93, 95% CI 0.50 to 1.74, P = 0.82, I(2) = 51%), intensive care unit mortality (OR = 0.84, 95% CI 0.55 to 1.29, P = 0.43, I(2) = 0%), duration of stay in the hospital (mean difference [MD] in days = -0.13, 95% CI -0.93 to 0.67, P = 0.75, I(2) = 46%), or duration of stay in the intensive care units (MD = -0.72, 95% CI -1.73 to 0.29, P = 0.16, I(2) = 68%). CONCLUSIONS: The use of probiotics was associated with a statistically significant reduction in the incidence of nosocomial pneumonia in critically ill patients. However, large, well-designed, randomized, multi-center trials are needed to confirm any effects of probiotics clinical endpoints such as mortality and length of ICU and hospital stay.