Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Efficacy and safety of drug-eluting beads bronchial arterial chemoembolization versus conventional bronchial arterial chemoembolization in lung cancer patients with hemoptysis.

Background: This study aimed to explore the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) compared with conventional bronchial arterial chemoembolization (cBACE) in lung cancer patients with hemoptysis. Materials & methods: Thirty-six lung cancer patients with hemoptysis treated by DEB-BACE or cBACE were retrospectively analyzed. Results: Technical success of BACE and clinical success of hemoptysis treatment were no different between DEB-BACE and cBACE (both p > 0.050), whereas DEB-BACE achieved increased total clinical response (p = 0.021), objective response rate (p = 0.035) and prolonged hemoptysis relapse-free survival (p = 0.013) compared with cBACE. The adverse event rates were similar between these two groups (all p > 0.05). Conclusion: DEB-BACE presents with higher tumor treatment response, prolonged hemoptysis relapse-free survival and comparable safety profiles compared with cBACE in lung cancer patients with hemoptysis.

Depletion of circ-BIRC6, a circular RNA, suppresses non-small cell lung cancer progression by targeting miR-4491.

Circular RNAs (circRNAs) are non-coding RNAs molecules consisting of a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. Accumulating evidence demonstrates that circRNAs are involved in the initiation and progression of human malignancies. In this study, we explored the expression profile and regulatory role of circ-baculoviral IAP repeat-containing 6 (circ-BIRC6), a circular RNA, in malignant behaviors in non-small cell lung cancer (NSCLC). Expression levels of circ-BIRC6 and miR-4491 were examined in NSCLC patient samples and cell lines using quantitative real time PCR (qRT-PCR). In vitro roles of circ-BIRC6 knockdown on cell viability, colony formation, and apoptosis were assessed using the CCK-8, colony formation assay, and flow cytometry, respectively. The interactions between circ-BIRC6 and miR-449 were assessed using luciferase reporter and qRT-PCR assays. The in vivo role of circ-BIRC6 knockdown on tumor growth and apoptosis was evaluated in a xenograft mouse model of NSCLC. We found that expression levels of circ-BIRC6 in NSCLC patient samples and cell lines were elevated. Small interfering RNA (siRNA)-mediated circ-BIRC6 knockdown suppressed cell proliferation, colony formation, migration and invasion, and promoted apoptosis in NCI-H460 and A549 cells. In addition, miR-4491 was identified as a tumor-suppressor miRNA in NSCLC and circ-BIRC6 functions as a molecular sponge for miR-4491. Furthermore, circ-BIRC6 knockdown suppressed Wnt2B/ß-catenin pathway. In vivo assay showed that depletion of circ-BIRC6 suppressed tumor growth, enhanced apoptosis, and decreased miR-4491 levels in a mouse xenograft model. These findings demonstrate that circ-BIRC6 functions as a critical regulator of proliferation and apoptosis via binding to and negatively regulating miR-4491, suggesting that circ-BIRC6 might be a potential target for treatment of NSCLC.

Expert panel consensus statement on the applications and precaution strategies of bronchoscopy in patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus with higher transmissibility compared with SARS coronavirus (SARS-CoV) and Middle East respiratory distress syndrome coronavirus. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an unprecedented global crisis that has not been experienced, which is still disrupting health systems, economies, and societies around the world by the rapid spread. Bronchoscopy plays an important role in diagnosis and therapy of pulmonary diseases, especially in patients with severe pulmonary infection, however, application of bronchoscopy in patients suspected or confirmed SARS-CoV-2 infection is extremely limited for the potential airborne transmission from aerosol generated during the procedure. This consensus statement was completed by expert panel of Interventional & Minimally Invasive Respiratory Committee of China Medical Education Association, and the issues were summarized as seven key topics to define the indications of bronchoscopy and matters needing attentions on the bronchoscopy procedures in patients with COVID-19, as well as the protective precaution strategies to avoid nosocomial SARS-CoV-2 infection.

Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old.

The use of corticosteroids has been controversial in viral pneumonia. In most cases, application of methylprednisolone in severe and critical viral pneumonia patients can quickly alleviate the symptoms of dyspnea and prevent disease progression. However, some scholars have confirmed that corticosteroids delayed the body's clearance of the virus. In our retrospective non-randomized study, 34 patients under 50 years old and diagnosed with coronavirus disease 2019 (COVID-19) were included. According to the given methylprednisolone treatment (n = 18) or not (n = 16), they were separated into two groups. By comparing the clinical data we concluded that corticosteroids therapy can effectively release COVID-19 symptoms such as persistent fever and difficult in breathing, improve oxygenation, and prevent disease progression. However, it can prolong the negative conversion of nucleic acids.

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy.

PURPOSE: The objective of the present study was to develop a liposomal drug delivery system based on combretastatin A4 (CA4) prodrugs modified with varying alkyl chains and investigate the in vitro drug conversion from prodrug and in vivo antitumor effect. METHODS: The prodrug of CA4 was synthesized with stearyl chloride (18-carbon chain), palmitoyl chloride (16-carbon chain), myristoyl chloride (14-carbon chain), decanoyl chloride (10-carbon chain), and hexanoyl chloride (6-carbon chain) at the 3'-position of the CA4. Subsequently, it was encapsulated with liposomes through the thin-film evaporation method. Furthermore, the characteristics of prodrug-liposome were evaluated using in vitro drug release, conversion, and cytotoxicity assays, as well as in vivo pharmacokinetic, antitumor, and biodistribution studies. RESULTS: The liposome system with loaded CA4 derivatives was successfully developed with nano-size and electronegative particles. The rate of in vitro drug release and conversion was reduced as the fatty acid carbon chain lengthened. On the contrary, in vivo antitumor effects were improved with the enlargement of the fatty acid carbon chain. The results of the in vivo pharmacokinetic and tissue distribution studies indicated that the reduced rate of CA4 release with a long carbon chain could prolong the circulation time and increase the drug concentration in the tumor tissue. CONCLUSION: These results suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy.

miRNA-19 promotes non-small-cell lung cancer cell proliferation via inhibiting CBX7 expression.

BACKGROUND: miR-19 is a critical carcinogenic miRNA that participates in important biological processes of human malignancies. CBX7 plays a key role in lung cancer development and progression. In the present study, for the first time, we investigated the correlation between miR-19 and CBX7 in non-small-cell lung cancer (NSCLC). METHODS: miR-19 expression in NSCLC tissues and lung cancer cell lines was detected using quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assay, qRT-PCR, Western blot, and immunohistochemical assay were conducted to identify the target reaction of miR-19 and CBX7. Moreover, the influence of miR-19 on lung cancer cell proliferation, migration, and invasion was studied including cell counting kit-8 assay, scratch assay, transwell assay, flow cytometry assay, and staining assays. RESULTS: miR-19 was overexpressed in NSCLC tissues and lung cancer cell lines. Luciferase reporter assay demonstrated that miR-19 could inhibit CBX7 expression via binding to the 3'-UTR of CBX7. Furthermore, miR-19 remarkably decreased CBX7 protein and mRNA expression. Additionally, overexpression of miR-19 could significantly enhance lung cancer cell proliferation and migration. CONCLUSION: miR-19 functions as a tumor accelerator promoting lung cancer cell proliferation through targeting CBX7 and inhibiting its expression.

Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism.

OBJECTIVES: To investigate the efficacy and safety of initial thrombolysis by recombinant tissue-type plasminogen activator (rt-PA) in compared with anticoagulant therapy in patients with acute intermediate-risk pulmonary embolism (PE).  Methods: Sixty-six patients with acute intermediate-risk PE were randomly assigned to receive rt-PA or LMWH between June 2014 and June 2017 in our department. We obtained information regarding the difference in the right ventricle/left ventricle (RV/LV) ratio, pulmonary artery systolic pressure (PASP), clinical symptoms improvement, PE-related mortality, hemodynamic decompensation, recurrent PE, and major and minor bleeding.  Results: In the rt-PA group, the mean PASP was reduced from 52.0±12.2 at baseline to 34.8±9.4 (p less than 0.001) and the mean RV/LV ratio was reduced from 1.26±0.22 at baseline to 0.96±0.18 (p less than 0.001) at 24 hours. In the LMWH group, the mean PASP was 53.4±12.8 at baseline and 48.5±11.9 at 24 hours (p=0.11), and the mean RV/LV ratio was 1.22±0.19 at baseline and 1.17±0.21 at 24 hours (p=0.31). In comparison with the LMWH group, there was a significant reduction in PASP and an improvement in the symptom severity in the rt-PA group. At 90 days, there was no difference in mortality, recurrent venous thromboembolism and major bleeding as a safety outcome, but increased minor bleeding and decreased hemodynamic decompensation occurred in the rt-PA group. Conclusions: In patients with acute intermediate-risk PE, low dose thrombolytic therapy is considered safe and effective, it can be recommended as an alternative option in clinical treatment.

Radiation resistance of the lung adenocarcinoma is related to the AKT-Onzin-POU5F1 axis.

Non-small cell lung carcinoma is the predominant type of lung cancer, and shows an easily developable tolerance to radiotherapy. Cancer stem cells are suggested to be involved in the resistance against therapies. Onzin might be accumulated during the process tumor overcoming the radiation stress. To address the relationship between Onzin, stemness and radiation resistance, we treated the lung cancer tumor bearing mice with radiaotherapy and observed the differences between radiation sensitive (RS) and resistant (RR) tumors. Immunohistochemistry and HE staining were used to observe Onzin and POU5F1 expression in tumor tissues. Quantitative realtime-PCR and Western blot were applied for Onzin and POU5F1 in tumors and cells. In-vitro cellular viability was assessed by CCK8 methods for tumor derived cells. The stably transfected A549 cell lines overexpressing Onzin were generated through lentivirus transfection. After radiotherapy, those RR adenocarcinoma tumors and cells derived from them showed an increased Onzin expression. Further, RR cells were found upregulated stemness, indicated by increased sphericity and proliferation, as well as POU5F1 expression. Next, we overexpressed Onzin in the A549 cells and found an elevated POU5F1 expression, increased proliferation, and enhanced sphericity. Moreover, this could be suppressed by the AKT inhibitor MK-2260. In vivo, the A549 cells overexpressing Onzin showed not only higher tumor formation capability and growth, but also a significant resistance to radiation. Taken together, RR tumors have upregulated Onzin and POU5F1 expression. Ectopic expression of Onzin promotes the POU5F1 expression as well as stemness functions, and confers adenocarcinomas the resistance to radiotherapy.

An optimized two-vial formulation lipid nanoemulsion of paclitaxel for targeted delivery to tumor.

The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency. Among them, TPLE-1 displayed higher PTX-loading, slower PTX-release and larger PTX-distribution in oil-phase, significantly reduced extraction by RES organs, increased tumor-uptake, showed stronger cytotoxicity against MCF-7 cells and more potent anticancer efficacy on MCF-7 tumor-bearing nude mice, and had greater plasma AUC0-∞ value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T1/2) in SD rats. It also exhibited the same in vivo efficacy as Taxol® and even produced less hemolysis and intravenous irritation. Moreover, its LD50 was 4.3-fold higher than that of Taxol®. All results demonstrate that TPLE-1 is a promising candidate drug due to its high tumor-accumulation and effectiveness, low toxicity, good safety and druggability in clinical application for the cancer therapy.

Identification of differentially expressed molecular functions associated with breast cancer using Gibbs sampling.

The aim of the present study was to identify differentially expressed molecular functions (DEMFs) for breast cancer using the Gibbs sampling approach. Molecular functions (MFs) were obtained on the basis of the Bayesian Approach for Geneset Selection package. Subsequently, MFs were converted into Markov chains (MCs) prior to calculating their probabilities, utilizing the MC Monte Carlo algorithm. DEMFs were identified with probabilities ≥0.8 and the gene compositions were studied. Finally, a co-expression network was constructed via the empirical Bayes method and a pathway enrichment analysis of genes in DEMFs was performed. A total of 396 MFs were identified and all transformed to MCs. With the threshold, 2 DEMFs (structural molecule activity and protein heterodimerization activity) were obtained. The DEMFs were comprised of 297 genes, 259 of which were mapped to the co-expression network. These 297 genes were identified to be enriched in 10 pathways, and ribosome was the most significant pathway. The results of the present study revealed 2 DEMFs (structural molecule activity and protein heterodimerization activity) which may be associated with the pathological molecular mechanisms underlying breast cancer, based on Gibbs sampling.

The association between the CC chemokine ligand 5 -28C>G gene polymorphism and tuberculosis susceptibility.

OBJECTIVES: To assess the association between chemotactic chemokine (C-C motif) ligand 5 (CCL5) -28C>G polymorphism and tuberculosis (TB) risk.   METHODS: PubMed, Web of Science, and WanFang were searched up to April 2015 for eligible studies on CCL5 -28C>G  polymorphism. Data was extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CI) were calculated.   RESULTS:  Eight case-control studies were extracted from 8 articles on the polymorphism involving 1852 TB cases and 2068 controls. The results of meta-analysis showed that significant reduced risks were found for the polymorphism with the risk of TB in Asians and Arabs as follows: OR=0.12, 95% CI=0.06-0.26, p=0.000 for mutant  homozygous (GG) versus wild-type homozygous (CC) for Asian descent, OR=0.14, 95% CI=0.07-0.28, p=0.000 for GG versus CC in the Arab descent.   CONCLUSION: Our findings demonstrated that CCL5 gene -28C>G   polymorphism might be a protective factor for the development of TB.

Innovative intragastric ascaridole floating tablets: Development, optimization, and in vitro-in vivo evaluation.

Gastro-floating tablets of ascaridole, a volatile oil were developed to prolong the gastric residence time and thereby, enhance local therapeutic efficacy. The tablets were optimized and prepared by direct compression techniques using hydroxypropylmethylcellulose (HPMC K15M) and polyethylene oxide (PEO WSRN-750) as hydrophilic matrices and calcium carbonate (CaCO3) as a gas-generating agent. In vitro evaluation of the prepared tablets was performed by determining the hardness, friability, content uniformity, and weight variation. In addition, floating lag time, total floating time, and drug release behavior were evaluated. Finally, optimized tablets were subjected to stability and in vivo gamma scintigraphy studies. Results showed that the formulated tablets were white, smooth, and flat in appearance and met the Chinese Pharmacopoeia (ChP) criteria for weight variation, drug content, and friability. The tablets had satisfactory buoyancy and sustained drug release profile that followed non-Fickian kinetics. In vivo gamma scintigraphy suggests that the floating tablet did not adhere to the stomach mucous but were retained in the stomach for extended periods of 5.80±0.50h following administration, indicating that gastro retentive time of ascaridole tablets increased owing to the floating principle.

Knockdown of S100A11 expression suppresses ovarian cancer cell growth and invasion.

As a member of the S100 protein family, S100A11 expression is often upregulated in human cancer tissues. Numerous studies have demonstrated that S100A11 plays an important role in the progression of cancer. However, the function of S100A11 in ovarian cancer remains elusive. In the present study, the expression levels of S100A11 were found to be significantly increased in ovarian cancer cells. Subsequently, the expression of S100A11 in ovarian cancer HO8910 cells was knocked down using short hairpin (sh)RNA in order to investigate the biological effects of S100A11 on the progression of the disease. The results demonstrated that knockdown of S100A11 by shRNA inhibited the proliferation, anchorage-independent growth, invasion and migration of HO8910 cells. In addition, knockdown of S100A11 increased the expression of E-cadherin and decreased the expression of Snail in HO8910 cells. Collectively, these results indicated that S100A11 was able to promote the growth, invasion and migration of ovarian cancer cells. Therefore, S100A11 may serve as a potential molecular target for the diagnosis and treatment of ovarian cancer.

Effectiveness and safety of diagnostic flexi-rigid thoracoscopy in differentiating exudative pleural effusion of unknown etiology: a retrospective study of 215 patients.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of diagnostic flexi-rigid thoracoscopy in differentiating exudative pleural effusion of unknown etiology. METHODS: A total of 215 patients with undiagnosed exudative pleural effusion were consecutively recruited between January 2011 and February 2013. Thoracoscopy was carried out under local anesthesia, and multisite pleural biopsies were performed using a flexi-rigid thoracoscope. The tolerance of the patients, surgical complications and postoperative pathological diagnosis rate were used to evaluate the effectiveness and safety of the thoracoscopy procedures. RESULTS: All patients, Karnofsky performance status (KPS) >70, could tolerate both the thoracoscopic surgery and pleural biopsy; there were no severe complications. Thoracoscopic findings included pleural hyperaemia, fibrinous adhesion, nodular bulge and fester. The pathological biopsy confirmed diagnoses of malignant tumor (97 cases), tuberculous pleuritis (91 cases), tuberculous empyema (one case), pulmonary schistosomiasis (one case) and unknown etiology (25 cases). The total diagnosis rate was 88.4%. Subcutaneous emphysema occurred in ten cases and fever in six cases, all of which recovered completely with conservative treatment. CONCLUSIONS: Flexi-rigid thoracoscopy had a high diagnosis rate, differentiating exudative pleural effusion of unknown etiology with satisfactory effectiveness and safety. There was high degree of relationship between thoracoscopic appearance and primary disease or tumor classification.

A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel.

A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug-delivery carrier for paclitaxel (PTX) was successfully developed. The formulation comprised a PEG400 solution of the drug (25mg/mL) that would be mixed with commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1mg/mL) prior to use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could significantly reduce extraction of reticuloendothelial system (RES) organs and increase tumor uptake, and exhibited more potent antitumor efficacy on bearing A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation response yet, and showed the same cytotoxicity against HeLa cells as Taxol®, and its LD50 was 2.7-fold higher than that of Taxol®, suggesting its good safety and druggability. In addition, TPLE displayed distinctly faster release of PTX, a greater proportion of PTX in phospholipids layer and a smaller share in oil phase than CPLE. From the Clinical Editor: This study demonstrates the feasibility and potential advantage of a novel PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in clinical application for the cancer therapy. FROM THE CLINICAL EDITOR: This team of investigators convincingly demonstrates the feasibility and potential advantage of a PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in cancer therapy, documenting superior safety and faster release of PTX compared to commercially available formulations.

Cordyceps sinensis extract suppresses hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells.

OBJECTIVE: To investigate the effects of a Chinese herb Cordyceps sinensis (C. sinensis) extract on hypoxia-induced proliferation and the underlying mechanisms involved. METHODS: This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells (PASMCs) was measured using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen (PCNA), c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry. RESULTS: We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs. CONCLUSION: Our results indicated that C. sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle (S+G2/M) phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension.

[Non-invasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a prospective cohort study].

OBJECTIVE: To investigate the clinical effect of non-invasive positive pressure ventilation (NPPV) on acute hypoxemic respiratory failure (AHRF), and to look for predictors of failure of NPPV in patients with AHRF. METHODS: In the cohort study, the clinical data of patients with AHRF in respiratory intensive care unit (RICU) of Beijing Chaoyang Hospital from January 2004 to December 2007 were collected prospectively. Patients were divided into successful group and failure group according to outcome of NPPV. Basic clinical information, NPPV mode and duration, vital signs, arterial blood gas analysis, and oxygenation index (PaO(2)/FiO(2)) before and 2 hours, 24 hours after NPPV were analyzed and compared between two groups. RESULTS: (1)The NPPV successful rate in 59 cases was 62.7% (37/59). (2)Compared with failure group, mean age, the ratio of patients in whom respiratory failure were induced by pulmonary infection were lower in successful group (both P<0.01). There was no difference in PaO(2)/FiO(2)between two groups before NPPV, but PaO(2)/FiO(2) in successful group was markedly higher than those of failure group after 2 hours and 24 hours of NPPV (P<0.05 and P<0.01), while heart rate (HR), respiratory rate (RR) were significantly lower (all P<0.01). (3)Logistic regression analysis identified age > or = 60 years [odds ratio (OR) 8.30, 95% confidence interval (CI) 2.49-27.60, P=0.002], pulmonary infection as underlying disease of respiratory failure (OR 6.19, 95%CI 1.90-20.20, P=0.027), PaO(2)/FiO(2)<150 mm Hg (1 mm Hg=0.133 kPa) after 2 hours of NPPV (OR 3.65, 95%CI 1.20-11.04, P=0.044), HR>100 times/min after 24 hours of NPPV (OR 7.45, 95%CI 2.15-25.58, P=0.010), and RR>30 times/min after 24 hours of NPPV (OR 7.26, 95%CI 1.88-24.49, P=0.018) as risk factors independently associated with failure of NPPV. CONCLUSION: NPPV can be the first line treatment for severe AHRF patients without absolute contraindication, while patients of older age with pulmonary infection, the risk of failure of NPPV is higher. Lack of improvement in cardiorespiratory and oxygenation condition after a short period of NPPV is the predictor of NPPV failure.