Weiqun He

Human alveolar epithelial type II cells in primary culture

Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator‐induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro‐surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)‐8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP‐A, SP‐B, SP‐C, SP‐D), CK‐8, KL‐6, αENaC, and aquaporin (AQP)‐3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP‐C, cytokines, and intercellular adhesion molecule‐1 was vigorous in response to stimulation with tumor necrosis factor‐α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.

A gloves-associated outbreak of imipenem-resistant Acinetobacter baumannii in an intensive care unit in Guangdong, China

BackgroundImipenem-resistant Acinetobacter baumannii (IRAB) is an important cause of hospital-acquired infection. We aimed to describe an outbreak of IRAB infection and to investigate its possible source in an intensive care unit.MethodsAn environmental investigation was undertaken. Antimicrobial susceptibility testing was performed by microdilution. These isolates were genotyped by use of repetitive extragenic palindromic polymerase chain reaction (rep-PCR; DiversiLab). The study included 11 patients infected with IRAB and 14 control patients free of IRAB. Case and control patients were compared for possible predisposing factors. A multifaceted intervention was implemented to control the outbreak.ResultsThirty-nine IRABs were isolated from patients and the environmental surveillance culture in August, November, and December 2011. All isolates were resistant to imipenem. The IRAB strains belonged to seven clones (A–G) by the use of rep-PCR. There were four epidemic clones (D–G) in the outbreak, and Clone D was predominant. For the case–control study, patients with chronic obstructive pulmonary disease were susceptible to infection with IRAB. The hospital mortality of the case group was significantly higher than that of the control group.ConclusionsThe outbreak strains were transmitted among infected patients and equipment by inappropriate use of gloves. A combination of aggressive infection control measures is essential for preventing recurrent nosocomial outbreaks of IRAB.

Survival Predictors for Severe ARDS Patients Treated with Extracorporeal Membrane Oxygenation: A Retrospective Study in China

Extracorporeal membrane oxygenation (ECMO) is increasingly being applied as life support for acute respiratory distress syndrome (ARDS) patients. However, the outcomes of this procedure have not yet been characterized in severe ARDS patients. The aim of this study was to evaluate the outcomes of severe ARDS patients supported with ECMO and to identify potential predictors of mortality in these patients. A total of 38 severe ARDS patients (aged 51.39±13.27 years, 32 males) who were treated with ECMO in the specialized medical intensive care unit of Guangzhou Institute of Respiratory Diseases from July 2009 to December 2014 were retrospectively reviewed. The clinical data of the patients on the day before ECMO initiation, on the first day of ECMO treatment and on the day of ECMO removal were collected and analyzed. All patients were treated with veno-venous ECMO after a median mechanical ventilation duration of 6.4±7.6 days. Among the 20 patients (52.6%) who were successfully weaned from ECMO, 16 patients (42.1%) survived to hospital discharge. Of the identified pre-ECMO factors, advanced age, a long duration of ventilation before ECMO, a higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, underlying lung disease, and pulmonary barotrauma prior to ECMO were associated with unsuccessful weaning from ECMO. Furthermore, multiple logistic regression analysis indicated that both barotrauma pre-ECMO and underlying lung disease were independent predictors of hospital mortality. In conclusion, for severe ARDS patients treated with ECMO, barotrauma prior to ECMO and underlying lung disease may be major predictors of ARDS prognosis based on multivariate analysis.

Original ResearchEducation, Research, and Quality ImprovementQuality Assessment of Clinical Practice Guidelines for Respiratory Diseases in China: A Systematic Appraisal

BACKGROUND There has been a significant increase in the publication of clinical practice guidelines (CPGs) for respiratory diseases in China. However, little is known about the quality and potential impacts of these CPGs. Our objective was to critically evaluate the quality of Chinese CPGs for respiratory diseases that were published in peer-reviewed medical journals. METHODS A systematic search of scientific literature published between 1979 and 2013 was undertaken to identify and select CPGs that were related to respiratory diseases. Four Chinese databases (the Chinese Biomedical Literature database [CBM], the China National Knowledge Infrastructure [CNKI], the VIP database, and the WANFANG database) were used. The quality of eligible guidelines was assessed independently by four reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. The overall agreement among reviewers was evaluated using an intraclass correlation coefficient. RESULTS A total of 109 guidelines published in 27 medical journals from 1979 to 2013 were evaluated. The overall agreement among reviewers was considered good (intraclass correlation coefficient, 0.838; 95% CI, 0.812-0.862). The scores of the six AGREE domains were low: 57.3% for scope and purpose (range, 4.2%-80.5%), 23.8% for stakeholder involvement (range, 2.8%-54.2%), 7.7% for rigor of development (range, 0%-27.1%), 59.8% for clarity and presentation (range, 22.2%-80.6%), 10.9% for applicability (range, 0%-22.9%), and 0.6% for editorial independence (range, 0%-16.7%). Scores for all guidelines were below 60%, and only three guidelines (2.8%) were recommended for clinical practice with modifications. CONCLUSIONS The quality of the guidelines was low, and stakeholder involvement, rigor of development, applicability, and editorial independence should be considered in the future development of CPGs for respiratory diseases in China.

Quality Assessment of Clinical Practice Guidelines for Respiratory Diseases in China: A Systematic Appraisal.

BACKGROUND There has been a significant increase in the publication of clinical practice guidelines (CPGs) for respiratory diseases in China. However, little is known about the quality and potential impacts of these CPGs. Our objective was to critically evaluate the quality of Chinese CPGs for respiratory diseases that were published in peer-reviewed medical journals. METHODS A systematic search of scientific literature published between 1979 and 2013 was undertaken to identify and select CPGs that were related to respiratory diseases. Four Chinese databases (the Chinese Biomedical Literature database [CBM], the China National Knowledge Infrastructure [CNKI], the VIP database, and the WANFANG database) were used. The quality of eligible guidelines was assessed independently by four reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. The overall agreement among reviewers was evaluated using an intraclass correlation coefficient. RESULTS A total of 109 guidelines published in 27 medical journals from 1979 to 2013 were evaluated. The overall agreement among reviewers was considered good (intraclass correlation coefficient, 0.838; 95% CI, 0.812-0.862). The scores of the six AGREE domains were low: 57.3% for scope and purpose (range, 4.2%-80.5%), 23.8% for stakeholder involvement (range, 2.8%-54.2%), 7.7% for rigor of development (range, 0%-27.1%), 59.8% for clarity and presentation (range, 22.2%-80.6%), 10.9% for applicability (range, 0%-22.9%), and 0.6% for editorial independence (range, 0%-16.7%). Scores for all guidelines were below 60%, and only three guidelines (2.8%) were recommended for clinical practice with modifications. CONCLUSIONS The quality of the guidelines was low, and stakeholder involvement, rigor of development, applicability, and editorial independence should be considered in the future development of CPGs for respiratory diseases in China.

A Multicenter Retrospective Review of Prone Position Ventilation (PPV) in Treatment of Severe Human H7N9 Avian Flu

Background Patients with H7N9 avian flu concurrent with severe acute respiratory distress syndrome (ARDS) usually have a poor clinical outcome. Prone position ventilation (PPV) has been shown to improve the prognosis of patients with severe ARDS. This study explored the effects of PPV on the respiratory and circulatory mechanics of H7N9-infected patients with severe ARDS. Methods Individuals admitted to four hospitals designated for H7N9 patients in Guangdong province were treated with PPV, and their clinical data were recorded before and after receiving PPV. Results Six of 20 critically ill patients in the ICU received PPV. After treatment with 35 PPV sessions, the oxygenation index (OI) values of the six patients when measured post-PPV and post-supine position ventilation (SPV) were significantly higher than those measured pre-PPV (P < 0.05).The six patients showed no significant differences in their values for respiratory rate (RR), peak inspiratory pressure (PIP), tidal volume (TV) or arterial partial pressure of carbon dioxide (PaCO2) when compared pre-PPV, post-PPV, and post-SPV. Additionally, there were no significant differences in the mean values for arterial pressure (MAP), cardiac index (CI), central venous pressure (CVP), heart rate (HR), lactic acid (LAC) levels or the doses of norepinephrine (NE) administered when compared pre-PPV, post-PPV, and post-SPV. Conclusion PPV provided improved oxygenation that was sustained after returning to a supine position, and resulted in decreased carbon dioxide retention. PPV can thus serve as an alternative lung protective ventilation strategy for use in patients with H7N9 avian flu concurrent with severe ARDS.

Using twitch tracheal airway pressure, negative inhale forced pressure, and Medical Research Council score to guide weaning from mechanical ventilation

Background Weaning from mechanical ventilation (MV) is an important and universal issue in critically ill patients, with no consensus that predicts weaning success. Twitch tracheal airway pressure (TwPtr) may be a more objective indicator of diaphragm function. The present study evaluated TwPtr relative to negative inspiratory force (NIF) or Medical Research Council (MRC) score, for predicting success of weaning from MV. Methods From December 2015 to March 2017, 62 patients were included who received invasive MV >48 hours and then underwent a test for spontaneous breathing. The NIF and MRC score were sequentially determined. The TwPtr measurement was performed via magnetic stimulation of the neck phrenic nerve. Results Weaning success was achieved by 54 patients (87.1%), including 30, 12, and 12 patients who experienced simple, difficult, and prolonged weaning, respectively. The areas under receiver operating characteristic curves (AUCs) for NIF, MRC score, and TwPtr were 0.778, 0.560, and 0.792. When TwPtr was combined with NIF, the sensitivity and specificity of weaning success were 96.3% and 75.0%, and AUC was 0.807. In the weaning success group, after correction for age, the AUC of TwPtr was 0.878, which differentiated the simple weaning from non-simple group. Conclusions TwPtr was superior to either NIF or MRC score for differentiating patients in the simple weaning group from those patients who experienced difficult, prolonged, or failed weaning. TwPtr combined with NIF may be used to predict weaning success better than the MRC score alone.

Prone position ventilation support for acute exacerbation of interstitial lung disease

Prone position ventilation (PPV) has been shown to improve oxygenation and decrease pulmonary vascular resistance and mortality in patients with severe acute respiratory distress syndrome (ARDS). Whether these benefits of PPV occur similarly in acute exacerbations of interstitial lung disease (ILD) is not clear. We retrospectively explored the use of PPV in acute exacerbation with ILD versus those with severe acute respiratory distress syndrome (severe ARDS).

MicroRNA-19b Mediates Lung Epithelial-Mesenchymal Transition via Phosphatidylinositol-3,4,5-Trisphosphate 3-Phosphatase in Response to Mechanical Stretch

&NA; Lung epithelial‐mesenchymal transition (EMT) plays an important role in ventilation‐associated lung fibrosis, which may contribute to the poor outcome of patients with acute respiratory distress syndrome. Because microRNAs control and modulate normal physiological and pathophysiological processes, we investigated the role of microRNAs in the development of acute respiratory distress syndrome‐associated EMT in response to mechanical stress. In the current study, primary human alveolar epithelial type II (AEII) cells were subjected to cyclic stretch that resulted in EMT profiles with decreased gene expression of cytokeratin‐8, E‐cadherin, and surfactant protein B, and increased expression of vimentin, &agr;‐smooth muscle actin, and N‐cadherin. Microarray analysis revealed that the expression of microRNA‐19b (miR‐19b) was up‐regulated in the AEII cells, and real‐time polymerase chain reaction showed that the expression of miR‐19b increased in both the AEII cells and the primary human small‐airway epithelial cells. Overexpression of miR‐19b in small‐airway epithelial cells promoted the mechanical stretch‐induced EMT phenotypes, whereas inhibition of miR‐19b attenuated it. The inhibitory effect of miR‐19b was attributed to enhanced signaling of phosphatidylinositol‐3,4,5‐trisphosphate 3‐phosphatase (PTEN), leading to inactivation of the AKT pathway. Restoration of PTEN expression or inhibition of AKT phosphorylation suppressed the mechanical stretch‐induced EMT phenotypes. We further demonstrated that the mechanical stretch‐induced miR19 expression was regulated by the focal adhesion kinase‐Rho pathway. In conclusion, we found that miR‐19b plays a key role in the development of the EMT phenotype through down‐regulation of PTEN in human lung epithelial cells in response to mechanical stretch. The miR‐19b‐PTEN signaling pathway may serve as a novel therapeutic target in the context of ventilator‐associated lung fibrosis.