Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice.

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTNCR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTNCR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTNCR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTNCR circuitry is essential for the induction and maintenance of the awake state associated with exploration.

Protective effects of progesterone on pulmonary artery smooth muscle cells stimulated with Interleukin 6 via blocking the shuttling and transcriptional function of STAT3.

BACKGROUND: Sex hormone paradox is a crucial but unresolved issue in the field of pulmonary artery hypertension (PAH), and is thought to be related to different pathogenic factors. Inflammation is one of pathological mechanisms of PAH development. However, effects of sex hormones on the pulmonary vasculature under the condition of inflammation are still elusive. METHODS: Interleukin-6 (IL-6) was used as a representative inflammatory stimulator. Effects of 17ß-estradiol or progesterone on human pulmonary artery smooth muscle cells (PASMCs) were measured under the condition of IL-6. Cell functions of proliferation and migration were measured by Alarmar Blue, EdU assay, wound-healing assay and transwell chambers. We explored further mechanisms using western blot, immunofluorescence, co-immunoprecipitation, qPCR and chromatin immunoprecipitation. RESULTS: Our results revealed that IL-6 promoted the proliferation of PASMCs, but progesterone could reverse the adverse effect of IL-6. The protective effect was dependent on progesterone receptor (PGR). By interacting with signal transducer and activator of transcription 3 (STAT3), activated PGR could reduce the IL-6-induced nuclear translocation of STAT3 and prevent STAT3-chromatin binding in PASMCs, leading to the decreased transcription of downstream CCND1 and BCL2. Alternatively, progesterone slightly decreased the phosphorylation of pro-proliferative Erk1/2 and Akt kinases and upregulated the anti-proliferative pSmad1-Id1/2 axis in IL-6-incubated PASMCs. CONCLUSIONS: Progesterone played a protective role on PASMCs in the context of IL-6, by blocking the functions of STAT3. Our findings might assist in explaining the clinical phenomenon of better prognosis for women with PAH.

Serum cartilage oligomeric matrix protein is decreased in patients with pulmonary hypertension: a potential protective factor.

Cartilage oligomeric matrix protein (COMP) was a protective factor in the cardiovascular system. Previous studies showed that hypoxia led to decreased COMP in rat models of pulmonary hypertension. However, the expression pattern of COMP in the pulmonary hypertension population was unclear. A total of 35 patients newly diagnosed with pulmonary hypertension and 70 controls were enrolled in the study. Circulating COMP concentrations of serum samples were measured by enzyme-linked immunosorbent assay and were analyzed the association with multiple clinical variables. Serum COMP concentrations in the pulmonary hypertension group were significantly declined in comparison with age- and sex-matched normal controls, especially in the female subgroup. No significant difference of COMP concentrations was observed in the etiological classification, heart function classification, and risk stratification. Major hemodynamic parameters, six-minute walk distance, N-terminal pro brain natriuretic peptide, and short-term prognosis were not statistically associated with COMP. However, some echocardiography parameters, like tricuspid annular plane systolic excursion and mean right atrial pressure, were found the negative relation to COMP concentrations. In conclusion, serum COMP levels were decreased in the patients with pulmonary hypertension, which was in accordance with its known biological effects. Its association with long-term prognosis was worth further exploring.

High flow nasal cannula versus conventional oxygen therapy in postoperative patients at high risk for pulmonary complications: A systematic review and meta-analysis.

BACKGROUND: The effects of high flow nasal cannula (HFNC) on postoperative patients at high risk for pulmonary complications(PC) are controversial. We aimed to further determine the effectiveness of HFNC in postoperative patients at high risk for PC by comparison to conventional oxygen therapy (COT). METHODS: We performed a comprehensive search that compared HFNC with COT in postoperative patients at high risk for PC. The main outcomes were length of hospital stay (hospital LOS) and respiratory complications. RESULTS: Six trials with a total of 733 patients were pooled in our final studies. Except for Hospital LOS (I2  = 53%, χ2  = 8.51, P = .07) and rate of intubation or non-invasive ventilation (NIV) for respiratory failure (RF) (I2  = 49%, χ2  = 1.97, P = .16) between HFNC and COT, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of intubation or NIV for RF (RR 0.23, 95% CI 0.08-0.66, P = .006) and rate of hypercapnia (RR 0.37, 95% CI 0.20-0.68, P = .002). As for the Hospital LOS, ICU LOS, rate of requirement of O2 after discontinuous and hypoxemia, HFNC did not show any advantage over COT. Trial Sequential Analysis (TSA) for Hospital LOS showed that monitoring boundaries were finally not surpassed and required information size (RIS) was not met. CONCLUSIONS: The available randomised controlled trials (RCTs) suggest that, among the postoperative patients at high risk for PC, HFNC therapy compared with the COT significantly reduces rate of incubation or NIV for RF and rate of hypercapnia, meanwhile is safely administered. Further large-scale, multicenter, randomised and controlled studies are needed to confirm our results.

Stool-based Xpert MTB/RIF Ultra assay as a tool for detecting pulmonary tuberculosis in children with abnormal chest imaging: A prospective cohort study.

OBJECTIVES: To evaluate the diagnostic efficacy of stool-based Xpert MTB/RIF Ultra assay versus other assays for the detection of paediatric pulmonary tuberculosis (PTB). METHODS: A prospective head-to-head comparative study was conducted from Dec 2017 to May 2019 in Shanghai Public Health Clinical Centre. Samples were collected from children (< 15 years) with abnormal chest imaging (X-ray or CT scan) results for the following tests: Ultra on stool sample (Ultra-Stool), Ultra on respiratory tract sample (Ultra-RTS), Xpert MTB/RIF assay (Xpert) on RTS (Xpert-RTS), acid-fast bacilli smear on RTS (AFB-RTS), and Mycobacterium tuberculosis (Mtb) culture on RTS (Culture-RTS). The results were compared with a composite reference standard. RESULTS: A total of 126 cases with paired results were analysed. Against a composite reference standard, Ultra-RTS demonstrated the highest sensitivity (52%) and specificity (100%). Ultra-Stool showed 84.1% concordance with Ultra-RTS, demonstrating 45.5% sensitivity and 94.7% specificity (kappa = 0.65, 95% CI= 0.51-0.79). The sensitivity of Ultra-Stool was similar to Mtb culture (45.5%, p = 1.000) and higher than AFB-RTS (27.3%, p < 0.05). Assay positivity was associated with age and infiltration range in chest imaging. CONCLUSIONS: When RTS is difficult to obtain, stool sample-based Ultra is a comparable alternative.

Diagnostic accuracy of the Berlin questionnaire and therapeutic effect of nasal continuous positive airway pressure in OSAHS patients with glucose metabolic dysfunction.

PURPOSE: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with alterations in glucose metabolism. The Berlin questionnaire (BQ) is effective in identifying subjects with high risk of OSAHS. However, its validity in patients with glucose metabolic dysfunction remains unclear. Our study aims to examine the diagnostic efficacy of the BQ in detecting OSAHS in patients with glucose metabolic dysfunction and to explore the effect of nasal CPAP on glucose metabolism. METHODS: Patients with glucose metabolic dysregulation were first asked to complete the BQ and then recruited for polysomnogram (PSG). The diagnostic accuracy of the BQ and the relationships between groups with normal glucose tolerance (NGT), elevated fasting blood glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were analyzed. Subjects with both OSAHS and glucose dysregulation received CPAP treatment and underwent an oral glucose tolerance test. Changes in apnea-hypopnea indices (AHI) and glycemic parameters were calculated to determine the efficacy of CPAP. RESULTS: Glycosylated hemoglobin and insulin levels were statistically different between the high-risk and low-risk groups according to the BQ. For diagnosis of subjects with OSAHS who also had glucose metabolic dysfunction, the sensitivity and specificity of the BQ using AHI cut-off values at 5 events per hour were 73% and 67%. CPAP therapy effectively reduced the blood glucose, HOMA-IR, and insulin levels. CONCLUSIONS: The BQ can be considered to be an effective and economical screening tool for patieints with OSAHS who also have glucose metabolic dysfunction. Treatment with CPAP may improve glycemic parameters.

Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case-control study.

BACKGROUND: It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case-control study. METHODS: A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period. RESULTS: Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs. CONCLUSIONS: Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice.

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.

Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway.

Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.

A novel method for sensitive determination of subclinical right ventricular systolic dysfunction in patients with obstructive sleep apnea.

OBJECTIVE: The aim of this study was to evaluate right ventricular (RV) regional systolic function and dyssynchrony in patients with newly diagnosed obstructive sleep apnea using real-time three-dimensional (3D) echocardiography. METHODS: Eighty-two subjects without hypertension, diabetes mellitus or any cardiac or pulmonary disease referred for evaluation of obstructive sleep apnea (OSA) had overnight polysomnography and complete echocardiographic assessment. According to the apnea hypopnea index (AHI), subjects were divided into four groups: group 1: control subjects (AHI < 5, n = 19), group 2: patients with mild OSA (AHI: 5-14, n = 21), group 3: moderate OSA (AHI: 15-30, n = 18), group 4: severe OSA (AHI > 30, n = 24). Real-time three-dimensional echocardiographic images were acquired to obtain RV regional (inflow, body and outflow) ejection fraction (EF) and time to minimum systolic volume in all subjects. RESULTS: Body weight and body mass index were greater in the severe and moderate OSA group than those of mild and controls group (P < 0.05). There was a significant decrease in mean SaO2 and the lowest SaO2 in severe OSA when compared to other groups (P < 0.001). Inflow EF and global EF were significantly lower in moderate and severe OSA patients than in controls (P < 0.05). Inflow EF and global EF were negatively correlated with AHI (r = -0.534 and r = -0.479, respectively, P < 0.001). CONCLUSIONS: In patients with OSA, RV inflow and global systolic function were impaired and were in inverse relationship with AHI. Evaluation of RV regional systolic function using real-time three-dimensional echocardiography may play a potential role in the noninvasive assessment of the severity of OSA.

Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea.

A Novel Method for Sensitive Determination of Subclinical Left-Ventricular Systolic Dysfunction in Subjects With Obstructive Sleep Apnea.

BACKGROUND: This study was to evaluate the subclinical left-ventricular (LV) systolic dysfunction with 2-dimensional speckle-tracking echocardiography in subjects with obstructive sleep apnea (OSA) with normal left ventricular ejection fraction and without any confounding disease that can cause myocardial dysfunction. METHODS: Nineteen healthy individuals and 60 subjects with OSA were included in this study. According to the severity of disease, OSA subjects were examined in 3 groups: mild, moderate, and severe OSA. LV apical views (for longitudinal strain) and short-axis views (for circumferential strain) were acquired for evaluation. Three-layer longitudinal strain values and circumferential strain values were determined for each view, and averages of these were used in comparison with other groups. RESULTS: Three-layer longitudinal strain values of the subjects with OSA were lower than those of the healthy individuals, and these values were decreased along with the OSA severity. The difference was significant between severe OSA and all other groups. Three-layer circumferential strain values of the OSA subjects were lower than those of the healthy individuals, and the difference was significant between the control group and all other groups. The apnea hypopnea index was found to be correlated with the 3-layer longitudinal strain (r = -0.74, P < .001; r = -0.72, P < .001; r = -0.69, P = <.001). CONCLUSIONS: Three-layer longitudinal and circumferential LV systolic functions in OSA subjects with normal left ventricular ejection fraction are deteriorated in the subclinical stage. Two-dimensional speckle-tracking echocardiography can be used as an effective method in the determination of subclinical myocardial dysfunction in subjects with OSA.

Obstructive sleep apnoea associated with syringomyelia.

Coexistence of obstructive sleep apnoea and syringomyelia is quite rare. This article discusses three cases of coexisting obstructive sleep apnoea and syringomyelia and looks at the possible mutual influences between the two diseases.

Fasting activated histaminergic neurons and enhanced arousal effect of caffeine in mice.

Caffeine, a popular psychoactive compound, promotes wakefulness via blocking adenosine A2A receptors in the shell of the nucleus accumbens, which projects to the arousal histaminergic tuberomammillary nucleus (TMN). The TMN controls several behaviors such as wakefulness and feeding. Fasting has been reported to activate the TMN histaminergic neurons to increase arousal. Therefore, we propose that caffeine may promote greater arousal under fasting rather than normal feeding conditions. In the current study, locomotor activity recording, electroencephalogram (EEG) and electromyogram recording and c-Fos expression were used in wild type (WT) and histamine H1 receptor (H1R) knockout (KO) mice to investigate the arousal effects of caffeine under fasting conditions. Caffeine (15mg/kg) enhanced locomotor activity in fasted mice for 5h, but only did so for 3h in normally fed animals. Pretreatment with the H1R antagonist pyrilamine abolished caffeine-induced stimulation on locomotor activity in fasted mice. EEG recordings confirmed that caffeine-induced wakefulness for 3h in fed WT mice, and for 5h in fasted ones. A stimulatory effect of caffeine was not observed in fasted H1R KO mice. Furthermore, c-Fos expression was increased in the TMN under fasting conditions. These results indicate that caffeine had greater wakefulness-promoting effects in fasted mice through the mediation of H1R.

The evaluation of efficacy and safety of sunitinib on EGFR-TKI pretreated advanced non-small cell lung cancer patients in China.

BACKGROUND: Sunitinib is an oral multitargeted tyrosine kinase inhibitor (TKI) exhibiting antiagiogenic and antitumor effects. OBJECTIVE: To evaluate the efficacy and potential toxicity of sunitinib therapy in advanced non-small cell lung cancer (NSCLC) patients in China. METHODS: From January 2009 to August 2011, 30 patients with stage IV NSCLC, who were pretreated with the epidermal growth factor receptor (EGFR)-TKIs and then received sunitinib, were retrospectively reviewed. Univariate and multivariate Cox proportional hazard regression analysis was performed to determine the potential prognostic risk factors influencing NSCLC survival. RESULTS: The median progression-free survival (PFS) and median overall survival (OS) of all 30 treated patients was 1.25 months [95% confidence interval (CI): 0.90-1.9 months] and 3.40 months (95% CI: 3.00-6.80 months), respectively. Cox regression analysis suggested that Eastern Cooperative Oncology Group (ECOG) performance status (PS) is predictive of both PFS (P=0.001) and OS (P<0.001). Common adverse events (AEs) included hand-foot syndrome (53.3%), mucositis (40.0%), rash (36.7%) and diarrhea (33.3%). CONCLUSION: No sign of overall clinical benefits of sunitinib was detected in patients with pretreated EGFR-TKIs. Most patients suffered AEs from mild to moderate severity. ECOG PS is highly associated with PFS and OS rate. Further studies in NSCLC are required to determine whether sunitinib is beneficial nor not.

Effect of noninvasive positive pressure ventilation on weaning success in patients receiving invasive mechanical ventilation: a meta-analysis.

BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has been proposed to shorten the duration of mechanical ventilation in intubated patients, especially those who fail initial weaning from invasive mechanical ventilation (IMV). However, there are also some discrepancies in terms of weaning success or failure, incidence of re-intubation, complications observed during study and patient outcomes. The primary objective of this update was to specifically investigate the role of NIPPV on facilitating weaning and avoiding re-intubation in patients intubated for different etiologies of acute respiratory failure, by comparing with conventional invasive weaning approach. METHODS: We searched randomized controlled trials (RCTs) comparing noninvasive weaning of early extubation and immediate application of NIPPV with invasive weaning in intubated patients from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Knowledge and Springerlink databases. Records from conference proceedings and reference lists of relevant studies were also identified. RESULTS: A total of 11 RCTs with 623 patients were available for the present analysis. Compared with IMV, NIPPV significantly increased weaning success rates (odds ratio (OR): 2.50, 95% confidence interval (CI): 1.46 - 4.30, P = 0.0009), decreased mortality (OR: 0.39, 95%CI: 0.20 - 0.75, P = 0.005), and reduced the incidence of ventilator associated pneumonia (VAP) (OR: 0.17, 95%CI: 0.08 - 0.37, P < 0.00001) and complications (OR: 0.22, 95%CI: 0.07 - 0.72, P = 0.01). However, effect of NIPPV on re-intubation did not reach statistical difference (OR: 0.61, 95%CI: 0.33 - 1.11, P = 0.11). CONCLUSIONS: Early extubation and immediate application of NIPPV is superior to conventional invasive weaning approach in increasing weaning success rates, decreasing the risk of mortality and reducing the incidence of VAP and complications, in patients who need weaning from IMV. However, it should be applied with caution, as there is insufficient beneficial evidence to definitely recommend it in terms of avoiding re-intubation.

[A retrospective study on the treatment of patients with chronic obstructive pulmonary disease by face mask mechanical ventilation].

OBJECTIVE: To assess the effect and the influencing factors in face mask mechanical ventilation (FMMV) for the treatment of COPD with respiratory failure (RF), and to compare the efficacy and efficiency of FMMV with endotracheal intubation mechanical ventilation (ETMV). METHODS: From 1991 to 2001, 4 ventilating periods were named initial, middle, late, and extending stage according to ventilators, face masks and mechanical ventilating methods. The results of FMMV in the 4 periods were compared. The results in patients with FMMV who reached the endotracheal intubation criteria were also compared with those in ETMV ones from 1988 to 1990. RESULTS: 385 patients with COPD and RF were admitted to RICU. The proportion of FMMV in all MV patients increased [48% (11/23), 79% (15/19), 85% (29/34), 91% (223/246)]; at the same time the effective rate of FMMV [46% (5/11), 67% (10/15), 83% (24/29), 89% (198/223)] and the total effective rate [71% (35/49), 71% (20/28), 81% (34/42), 88% (234/266)] also increased. 83 percent of the patients who suffered from severe disturbances of consciousness in the late and extending stage were successfully weaned from FMMV. Complications including the rates of nasal bridge erosion [27% (3/11), 13% (2/15), 7% (2/29), 2% (4/223)] and the rates of stomach distension [46% (5/11), 40% (6/15), 21% (6/29), 5% (11/223)] all decreased. The ventilation times and length of stay were significantly shorter than those in patients with ETMV. The rate of nosocomial pneumonia and the mortality of inpatients were significantly lower. CONCLUSION: The ventilating techniques, ventilators and face masks were the main factors influencing FMMV results. FMMV could be used rationally for most COPD patients with RF as a valuable alternative to ETMV.