Exploration of the minimal clinically important difference value of the 3-min simulated pedal motion in patients with chronic obstructive pulmonary disease: A self-controlled prospective clinical trial.

BACKGROUND: To help elderly patients with severe or very severe chronic obstructive pulmonary disease (COPD) with pulmonary rehabilitation, we have developed Zheng's supine rehabilitation exercise (ZSRE). Currently, none of the terminal or critically ill patients with severe exercise limitation can complete the 6-min walking distance (6MWD) and cardiopulmonary exercise testing (CPET). METHODS: In this study, we discuss the definition of the standardized 3-min simulated pedal motion (3MSPM) test and its operational specifications. Also, we evaluate the minimal clinically important difference (MCID) value of the 3MSPM. RESULTS: The results showed that the mMRC score of COPD patients with acute exacerbation of dyspnea was progressively reduced from the second day of respiratory rehabilitation, and the difference between the first and seventh days was statistically significant (p < 0.000, χ2 = 176.664). 6MWD increased progressively, and the difference between 6MWD on day 1-7 was statistically significant (p = 0.024, F = 2.443). The difference between 3MSPM on day 1-7 was also statistically significant (p < 0.000, F = 4.481). Further analysis showed that 6MWD was negatively correlated with mMRC (p < 0.000, OR = -0.524). 3MSPM was positively correlated with 6MWD (p < 0.000, OR = 0.640) but negatively correlated with mMRC (p < 0.000, OR = -0.413). There is a linear regression relationship between 6MWD and 3MSPM, that is, 6MWD = 14.151 + 0.301 * 3MSPM, adjusted R2 = 0.401. CONCLUSION: Based on the regression equation, 3MSPM can predict 6MWD, and it can be used as a simple exercise endurance method to evaluate patients with safety hazards in underground activities or who cannot complete the 6MWD test. The minimum clinically important difference value is increased by 23.

Effect of hydrogen/oxygen therapy for ordinary COVID-19 patients: a propensity-score matched case-control study.

BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.

[A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period].

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and ß diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS: FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.

Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty.

Background: Ambroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance. Methods: This study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population. Results: Between 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: -0.29; 95% CI: -0.53 to -0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: -0.18; 95% CI: -0.34 to -0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported. Discussion: In hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

Research on the role of cellular autophagy in the sensitivity of human tongue cancer cells to radiotherapy and chemotherapy.

OBJECTIVE: This paper aims to investigate the role of cisplatin-induced autophagy in human tongue squamous carcinoma Tca8113 cells. METHODS: After inhibiting the expression of autophagic proteins with different autophagy inhibitors (3-methyladenine, chloroquine), the sensitivity of human tongue squamous cell carcinoma (Tca8113) cells to killing by gradient concentrations of cisplatin and gradient doses of radiation was detected using a colony formation assay. Further, the changes of autophagy expression in Tca8113 cells that had been treated with cisplatin and radiation were detected using western immunoblot, GFP-LC3 fluorescence and transmission electron microscopy. RESULTS: The sensitivity of Tca8113 cells to cisplatin and radiation was significantly increased (P < 0.05) after reducing autophagy expression using different autophagy inhibitors. Meanwhile, the expression of autophagy in the cells was significantly increased by cisplatin and radiation treatment. CONCLUSION: Tca8113 cells upregulated autophagy under the effect of either radiation or cisplatin, and the sensitivity of Tca8113 cells to cisplatin and radiation could be improved by inhibiting autophagy using multiple pathways.

Compliance and rehabilitation effects of Zheng's supine rehabilitation exercise performed at home among patients with chronic obstructive pulmonary disease: a retrospective study.

Background: Zheng's supine rehabilitation exercise (ZSRE) can be performed by elderly patients with the acute exacerbation of severe or extremely severe chronic obstructive pulmonary disease (COPD) with high safety and compliance and was helpful for their recovery. Investigation is warranted of the compliance and rehabilitation effects of ZSRE performed at home in patients with COPD. Methods: We performed telephone interviews with 157 patients with COPD who were hospitalized on the 26th floor of the National Clinical Research Center for Respiratory Disease and who received COPD education and ZSRE training from 1 September 2015 to 31 August 2016. We retrospectively analyzed the patients' compliance with performing ZSRE at home after discharge and the frequency of hospitalization for treatment of acute exacerbation in both the previous and subsequent years. Results: Among the 157 patients, 66 failed to complete home ZSRE after discharge (non-rehabilitation group), 41 performed home ZSRE once a day after discharge (one-session rehabilitation group), and 50 performed home ZSRE at least twice a day after discharge (multiple-session rehabilitation group). The home ZSRE compliance rate was 57.96% (91/157). There were no significant differences in the mean number of hospitalizations in the year prior to receiving COPD education and ZSRE training among the non-rehabilitation group (1.06±0.75), one-session rehabilitation group (1.27±0.78), and multiple-session rehabilitation group (1.16±0.91). However, there was a significant difference in the mean number of hospitalizations among the groups in the year following discharge (1.44±1.17, 0.78±0.82, and 0.66±0.75, respectively). The number of hospitalizations significantly increased in the non-rehabilitation group and significantly decreased in the one- and multiple-session rehabilitation groups. Conclusions: Home ZSRE can be performed with high compliance by elderly patients with severe or extremely severe COPD and can reduce the number of readmissions.

Identification of genetic variants of the IL-22 gene in association with an altered risk of COPD susceptibility.

The incidence of chronic obstructive pulmonary disease (COPD) is related to the interaction between environmental exposure and genetic factors. Far more than 15% of smokers eventually develop COPD. In addition to smoking, genetic susceptibility may be another factor in the development of COPD. IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis. Here, we conducted a case-control study to evaluate the association between IL-22 tag-single nucleotide polymorphisms (SNPs) and COPD risk. Four tag-SNPs (rs2227478, rs2227481, rs2227484 and rs2227485) were identified according to linkage disequilibrium (LD) analysis in 30 healthy controls. A total of 513 COPD cases and 504 controls were recruited to perform an association study between these four tag-SNPs and COPD risk. We found that the "C" allele of rs2227478T>C and the "T" allele of rs2227481C>T were obviously related to decreased COPD susceptibility. Genetic model analysis showed that rs2227478T>C and rs2227481C>T were significantly associated with a decreased risk of COPD under dominant models after adjusting for the above factors. In the recessive model, rs2227485T>C was obviously associated with decreased COPD risk. Our data showed that only rs2227485T>C was associated with a decreased COPD risk after Bonferroni correction. The eQTL analysis showed that rs2227485T>C was significantly associated with IL-22 expression. The pGL4-rs2227485-C gene reporter had a higher promoter activity than pGL4-rs2227485-T. In our study, rs2227485T>C, located in the promoter region of IL-22, was associated with a decreased risk of COPD and increased IL-22 promoter activity, suggesting that this variant might modulate COPD susceptibility.

[Effect of electroacupuncture on small airway function in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO2/kg], minute ventilation [VE], the percentage of oxygen pulse [VO2/HR] in predictd value, maximal minute ventilation [VEmax], ventilatory equivalent for oxygen [VE/VO2], ventilatory equivalent for carbon dioxide [VE/VCO2]), 6-minute walk distance (6MWD), the total score of COPD assessment test (CAT), the modified British Medical Research Council (mMRC) score and COPD comprehensive grade. RESULTS: After treatment, FVC%, MVV%, MEF75%, MEF50%, VO2/kg%, METs%, VEmax, VO2/HR%, 6MW and the total CAT score were all improved as compared with those before treatment in the observation group (P<0.05, P<0.01). After treatment, MEF75% and the total CAT score were reduced as compared with those before treatment in the control group (P<0.05). After treatment, MVV%, MEF50%, VO2/kg%, METs%, VEmax and 6MWD in the observation group were all better than those in the control group (P<0.05, P<0.01). CONCLUSION: Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.

Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial.

BACKGROUND: To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety. RESULTS: Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (- 5.3 vs. - 2.4 point; difference: - 2.75 [95% CI - 3.27 to - 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (- 11.00 vs. - 6.00, p < 0.001). Changes in pulmonary function, arterial blood gas and noninvasive oxygen saturation did not differ significantly between groups as well as other endpoints. AEs were reported in 34 (63.0%) patients in Hydrogen/oxygen group and 42 (77.8%) in Oxygen group. No death and equipment defects were reported during study period. CONCLUSIONS: The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile. TRIAL REGISTRATION: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1 .

Erratum to hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial.

[This corrects the article DOI: 10.21037/jtd-2020-057.].

A protective polymorphism in MMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population-based studies.

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract-treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels.

Effect of short-term inhalation of warm saline atomised gas on patients with non-cystic fibrosis bronchiectasis.

OBJECTIVE: Secretion clearance is advocated in non-cystic fibrosis bronchiectasis, but is often neglected in clinical treatment. The present study aimed to investigate the effect of inhaled 0.9% normal saline by ultrasonic nebuliser with warming (UNW) in stable non-cystic fibrosis bronchiectasis patients with purulent sputum. METHODS: 27 stable patients were enrolled in a randomised crossover trial comprising 3 months of daily UNW aerosol therapy compared with 3 months of daily oral expectorant treatment. The outcomes were quality of life (assessed via the Leicester cough questionnaire (LCQ)), sputum characteristics, pulmonary function, 6-min walk distance (6MWD) and acute exacerbation frequency. RESULTS: Compared with baseline, the sputum viscosity, sputum colour, LCQ score and 6MWD were significantly improved with UNW (p<0.05), and the improvements in sputum colour, LCQ score, 6MWD and inspirational capacity with UNW were significantly better than those achieved via treatment with oral expectorant (p<0.05). There were no significant differences between treatments in pulmonary function, sputum cytology classification and inflammatory factors of sputum. CONCLUSION: UNW aerosol therapy in non-cystic fibrosis bronchiectasis has small yet significant benefits. However, UNW does not improve the degree of inflammation.

The effectiveness, safety and compliance of Zheng's supine rehabilitation exercise as a rehabilitation programme among elderly patients with AECOPD.

PURPOSE: We investigated the effectiveness, safety and compliance of Zheng's Supine Rehabilitation Exercise (ZSRE) as a rehabilitation programme among elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). PATIENTS AND METHODS: About 82 elderly patients with AECOPD were divided into a rehabilitation group and control group on their admission day, and both groups received routine medical treatment. Patients in the rehabilitation group started ZSRE on the second day of admission and continued until 8 weeks after discharge. RESULTS: At the 9th week after discharge, the COPD Assessment Test (CAT), 6-minute walking distance (6MWD) and Modified Medical Research Council Dyspnea Scale (mMRC) in the rehabilitation group were all significantly better than those in the control group (P < 0.01; P < 0.01; and P < 0.05, respectively). In the rehabilitation group, the CAT and 6MWD were significantly improved in the 9th week after discharge as compared with those at admission or discharge, and mMRC was significantly improved at the 9th week after discharge as compared with that at admission (all P < 0.01). CONCLUSION: ZSRE can be performed by elderly patients with the acute exacerbation of severe or extremely severe COPD with high safety and compliance and was helpful for their recovery.

The efficacy of adding budesonide/formoterol to ipratropium plus theophylline in managing severe chronic obstructive pulmonary disease: an open-label, randomized study in China.

BACKGROUND: Patients diagnosed with chronic obstructive pulmonary disease (COPD) in China are commonly prescribed ipratropium plus theophylline (I+T) therapy. Studies have shown that an inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) combination is also efficacious in reducing symptoms and exacerbations. This study evaluated the efficacy and tolerability of adding budesonide/formoterol (BUD/FORM) to I+T in Chinese patients with severe COPD. METHODS: A randomized, parallel-group, open-label, multicenter phase IV study (Clinical Trials.gov identifier: NCT01415518) was conducted in China. Patients received either BUD/FORM (160/4.5 µg; two inhalations twice daily [bid] via Turbuhaler®) + I (20 µg per inhalation, two inhalations four times daily) + T (100 mg bid) or I+T alone for 12 weeks. The primary efficacy variable was change from baseline in predose forced expiratory volume in 1 s (FEV1). RESULTS: A total of 584 patients were randomized equally between treatment groups. At the end of the study, the BUD/FORM plus I+T group displayed significant improvements in predose FEV1 versus the I+T group (between-group difference 6.9%; 95% confidence interval [CI]: 4.3, 9.6; p < 0.0001). Forced vital capacity, inspiratory capacity, peak expiratory flow and health-related quality of life (HRQoL) scores were significantly improved (all p < 0.0001) and exacerbation frequency was reduced (43.5% reduction; rate ratio 0.565, 95% CI 0.325, 0.981; p = 0.0425) with BUD/FORM plus I+T versus I+T alone. CONCLUSION: Patients with severe COPD in China treated with BUD/FORM plus I+T showed significant improvements in lung function and HRQoL and a reduction in exacerbations compared with I+T alone. Both treatments were well tolerated and no safety concerns were noted. The reviews of this paper are available via the supplemental material section.

Author Correction: Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effects of exercise-induced dyspnoea on the aspiration rate among patients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: To use radionuclide imaging to investigate silent aspiration among patients recovering from an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We also evaluated the effects of exercise-induced dyspnoea on silent aspiration in COPD patients. PATIENTS AND METHODS: Recovering AECOPD patients admitted to the First Affiliated Hospital of Guangzhou Medical University between December 2013 and December 2015 were selected for the radionuclide aspiration test along with healthy volunteers of similar age. Aspiration-negative AECOPD patients were randomized into two subgroups. Patients in group A performed symptom-limited incremental cycle exercise test. Patients in group B were resting on the exercise bicycles. Aspiration-negative healthy volunteers performed symptom-limited incremental cycle exercise test (group C). Three groups performed a radionuclide aspiration test 30 min after exercise. RESULTS: The silent aspiration rates among recovering AECOPD patients and healthy volunteers were 44.19% (57/129) and 0 (0/18) (P = 0.00). The aspiration rates in groups A and B were 33.33% (10/30) and 23.33% (7/30), (P = 0.39) and groups A and C were 33.33% (10/30) and 0% (0/12), (P = 0.04). CONCLUSION: Recovering AECOPD patients had significantly higher silent aspiration rates than healthy volunteers of similar age. The evidence is not strong enough to support the patients with exercise-induced dyspnoea-increased aspiration rate.

RNA Sequencing Analyses of Gene Expression during Epstein-Barr Virus Infection of Primary B Lymphocytes.

Epstein-Barr virus (EBV) infection of human primary resting B lymphocytes (RBLs) leads to the establishment of lymphoblastoid cell lines (LCLs) that can grow indefinitely in vitro EBV transforms RBLs through the expression of viral latency genes, and these genes alter host transcription programs. To globally measure the transcriptome changes during EBV transformation, primary human resting B lymphocytes (RBLs) were infected with B95.8 EBV for 0, 2, 4, 7, 14, 21, and 28 days, and poly(A) plus RNAs were analyzed by transcriptome sequencing (RNA-seq). Analyses of variance (ANOVAs) found 3,669 protein-coding genes that were differentially expressed (false-discovery rate [FDR] < 0.01). Ninety-four percent of LCL genes that are essential for LCL growth and survival were differentially expressed. Pathway analyses identified a significant enrichment of pathways involved in cell proliferation, DNA repair, metabolism, and antiviral responses. RNA-seq also identified long noncoding RNAs (lncRNAs) differentially expressed during EBV infection. Clustered regularly interspaced short palindromic repeat (CRISPR) interference (CRISPRi) and CRISPR activation (CRISPRa) found that CYTOR and NORAD lncRNAs were important for LCL growth. During EBV infection, type III EBV latency genes were expressed rapidly after infection. Immediately after LCL establishment, EBV lytic genes were also expressed in LCLs, and ∼4% of the LCLs express gp350. Chromatin immune precipitation followed by deep sequencing (ChIP-seq) and POLR2A chromatin interaction analysis followed by paired-end tag sequencing (ChIA-PET) data linked EBV enhancers to 90% of EBV-regulated genes. Many genes were linked to enhancers occupied by multiple EBNAs or NF-κB subunits. Incorporating these assays, we generated a comprehensive EBV regulome in LCLs.IMPORTANCE Epstein-Barr virus (EBV) immortalization of resting B lymphocytes (RBLs) is a useful model system to study EBV oncogenesis. By incorporating transcriptome sequencing (RNA-seq), chromatin immune precipitation followed by deep sequencing (ChIP-seq), chromatin interaction analysis followed by paired-end tag sequencing (ChIA-PET), and genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen, we identified key pathways that EBV usurps to enable B cell growth and transformation. Multiple layers of regulation could be achieved by cooperations between multiple EBV transcription factors binding to the same enhancers. EBV manipulated the expression of most cell genes essential for lymphoblastoid cell line (LCL) growth and survival. In addition to proteins, long noncoding RNAs (lncRNAs) regulated by EBV also contributed to LCL growth and survival. The data presented in this paper not only allowed us to further define the molecular pathogenesis of EBV but also serve as a useful resource to the EBV research community.

Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited treatment options. Hydrogen (H2) has been shown to be anti-oxidative and anti-inflammatory. This study aimed to evaluate the beneficial effects of H2 inhalation on COPD development in mice. METHODS: A COPD mouse model was established in male C57BL mice by cigarette smoke (CS) exposure. The H2 intervention was administered by atomisation inhalation. Lung functions were assessed by using Buxco lung function measurement system. The inflammatory cells were counted and the levels of IL-6 and KC in BALF were assayed with ELISA. The lung tissue was subjected to H&E or PAS or Masson's trichrome stain. Furthermore, 16HBE cells were used to evaluate the effects of H2 on signaling change caused by hydrogen peroxide (H2O2). H2O2 was used to treat 16HBE cells with or without H2 pretreatment. The IL-6 and IL-8 levels in cell culture medium were measured. The levels of phosphorylated ERK1/2 and nucleic NF-κB in lungs and 16HBE cells were determined. RESULTS: H2 ameliorated CS-induced lung function decline, emphysema, inflammatory cell infiltration, small-airway remodelling, goblet-cell hyperplasia in tracheal epithelium and activated ERK1/2 and NF-κB in mouse lung. In 16HBE airway cells, H2O2 increased IL-6 and IL-8 secretion in conjunction with ERK1/2 and NF-κB activation. These changes were reduced by H2 treatment. CONCLUSIONS: These findings demonstrated that H2 inhalation could inhibit CS-induced COPD development in mice, which is associated with reduced ERK1/2 and NF-κB-dependent inflammatory responses.