Background Flexible bronchoscopy (FB) is commonly performed in patients with acute respiratory failure (ARF), but the procedure can exacerbate hypoxemia and increase the need for respiratory support. The impact of high-flow nasal oxygen (HFNO) therapy during nasal FB in patients with ARF remains uncertain, as prior studies have focused primarily on oxygenation rather than clinical outcomes. We aimed to evaluate whether HFNO therapy via a single-prong cannula interface (HFNO-SPC) could reduce the need for respiratory support escalation within 24 h after FB compared to standard oxygen therapy (SOT). Methods We conducted a two-center, open-label, randomized controlled trial comparing HFNO-SPC to SOT in patients undergoing FB. The primary outcome was escalation of respiratory support within 24 h after FB, defined as the requirement for invasive mechanical ventilation (IMV), noninvasive ventilation (NIV), or HFNO, or as increases in support parameters without changing the mode of respiratory support. The secondary outcome was a hierarchical composite of these escalation events. Electrical impedance tomography (EIT) monitoring was performed during FB to assess tidal volume and end-expiratory lung volume changes. Results A total of 160 patients were randomized to either the HFNO-SPC group (n = 80) or the SOT group (n = 80), and all were included in the intention-to-treat analysis. HFNO-SPC significantly reduced the incidence of respiratory support escalation compared to SOT (15.0% vs. 33.8%, P = 0.006). Hierarchical analysis of the composite secondary outcome supported the primary findings (31.6% vs 12.1%, P = 0.004). Additionally, HFNO-SPC resulted in a lower intubation rate within 24 h (7.5% vs. 20.0%, P = 0.022). EIT measurements showed smaller reductions in tidal impedance variation (TIV) during FB and less pronounced changes in end-expiratory lung impedance (ΔEELI) during and after FB in the HFNO-SPC group. Conclusions In patients with ARF, HFNO-SPC significantly reduced the proportion of patients requiring respiratory support escalation within 24 h after FB compared with SOT. This finding was consistent across a hierarchical analysis of clinically ranked outcomes. Trial Registration ClinicalTrials.Gov: NCT 05759832. Registered 27 February 2023.

Niemann-Pick disease type C (NPC) is an autosomal recessive hereditary disease in which sphingomyelin and cholesterol are deposited in various organs of the body. The clinical manifestations of NPC include neurologic symptoms and cataplexy; other symptoms related to sleep have seldom been reported. One previous study described various sleep disorders including chronic insomnia, obstructive sleep apnea, restless legs syndrome, and rapid eye movement sleep behavior disorder, thus suggesting that sleep disorders in patients with NPC are more prevalent than previously thought and warrant close attention. Here, we describe sleep disorders in 2 patients with NPC and discuss the clinical characteristics and, for the first time, discuss potential pathogenic mechanisms underlying sleep disorders in such patients.

Changes in nasal resistance (NR) during postural changes are influenced by venous filling pressure and autonomic nervous system mediation, and heart rate variability (HRV) can reflect changes in the autonomic nervous system. This study aimed to explore the regulatory mechanisms of NR in patients with obstructive sleep apnea (OSA) during postural changes. Healthy controls (apnea-hypopnea index < 5 events/h) and patients with OSA were recruited. NR and electrocardiogram data were collected in sitting, supine, left-lateral, and right-lateral postures. HRV parameters were obtained by analyzing the electrocardiogram data from each posture. Subgroups were divided according to sitting–supine NR changes, and HRV parameters were compared between different postures and groups/subgroups. In total, 34 healthy controls and 39 patients with OSA (mean apnea-hypopnea index 34.34 ± 22.44 events/h) were recruited. During sitting–supine postural changes, the NR increased in the control group but did not change significantly in the OSA group. None of the autonomic nervous system–related HRV parameters changed significantly. After the groups were divided into NR-elevated and NR-unchanged subgroups, sympathetic activity–related HRV parameters were higher in the NR-unchanged subgroup but only statistically significant in the OSA group. When comparing the left and right postures, there was no significant change in NR; however, the OSA group had lower parasympathetic activity–related HRV parameters when in the right posture. During postural changes from the sitting to supine positions, the total NR increases, and this increment is smaller in patients with OSA. This is likely due to overregulation of sympathetic activity, which may occur in patients with OSA.

Abstract Aims/Introduction To estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China. Materials and Methods Hospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ2‐test was used to evaluate differences between groups regarding the prevalence, and demographic and other clinical parameters. Results A total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5/h), moderate‐to‐severe (apnea hypopnea index ≥15/h) and severe (apnea hypopnea index ≥30/h) OSAS was 66.3% (95% confidence interval 60.8–71.6%), 35.6% (95% confidence interval 30.3–41.2%) and 16.5% (95% confidence interval 12.5–21.1%), respectively. Central and mixed apnea contributed 12% to all sleep‐disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self‐reported snoring and apnea, and diabetes complications. Conclusions Guidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.

Background: Glucocorticoid (GC) resistance results in unsatisfactory outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Previous studies have shown that calcitriol, the active form of vitamin D, alone or in combination with corticosteroids, exerts crucial immunomodulatory effects on inflammatory responses. However, whether vitamin D can improve the effect of GCs to attenuate inflammation in the epithelium of CRSwNP remains unclear. Methods: A human bronchial epithelial cell line (Beas-2B) and primary human nasal epithelial cells (HNECs) obtained from 10 patients with CRSwNP were exposed to lipopolysaccharide (LPS) for 24 h to establish an inflammation model. LPS-stimulated HNECs and Beas-2B cells were treated with/without dexamethasone in the presence or absence of calcitriol pretreatment for 24 h. The expression levels of interleukin-6 (IL-6) mRNA and protein were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Toll-like receptor 4 (TLR4)/NF-κB pathway related markers were examined by western blotting. One-way ANOVA or the Kruskal-Wallis test with post hoc analysis were used for multiple comparisons among groups. Results: The production of IL-6 in Beas-2B cells and primary HNECs after LPS stimulation was significantly increased, which could be inhibited by dexamethasone or calcitriol alone. However, significant inhibition of IL-6 production was observed in the calcitriol plus dexamethasone group. Further analysis showed that calcitriol could enhance the effect of dexamethasone in inhibiting LPS-induced overexpression of TLR4, Myd88, and phosphorylation of p65. Conclusion: Our findings demonstrated that vitamin D could improve the effect of GCs to alleviate the level of IL-6 induced by LPS via the TLR4/NF-κB pathway in human respiratory epithelial cells.

Introduction: Currently, there is a lack of evidence on the utilization of high-flow nasal cannula (HFNC) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) accompanied by hypercapnic respiratory failure. We aimed to explore the efficacy and safety of HFNC compared with conventional oxygen therapy (COT) in such patients. Methods: This was a prospective, randomized, controlled trial. Patients with AECOPD with a baseline arterial blood gas pH >= 7.35, PaO2 < 60 mmHg, and PaCO2 > 45 mmHg were enrolled. The primary endpoint was treatment failure, which needs mechanical ventilation. Results: A total of 320 patients were randomized to either the HFNC group (n = 160) or the COT group (n = 160). Sixteen (10.0%) patients in the HFNC group had treatment failure during hospitalization, which was significantly lower than the COT group figure of 31 (19.4%) patients (p = 0.026). Twenty-four hours after recruitment, the PaCO2 of the HFNC group was lower than that of the COT group (54.1 +/- 9.79 mmHg vs 56.9 +/- 10.1 mmHg, p = 0.030). PaCO2 higher than 59 mmHg after HFNC for 24 h was identified as an independent risk factor for treatment failure [OR 1.078, 95% CI 1.006-1.154, p = 0.032]. Conclusion: In AECOPD patients with acute compensated hypercapnic respiratory failure, HFNC improved the prognosis compared with COT. Therefore, HFNC might be considered for first-line oxygen therapy in select patients.

OBJECTIVE:Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for many clinical complications. However, how OSAHS cause multiple organ injury and initiate inter-organ communication remains unclear. Moreover, despite it is well-recognized that chronic intermittent hypoxia (CIH) is a main feature of OSAHS, specific contribution of CIH to overall OSAHS-initiated pathological complications remains unclear. This study aimed to use an unbiased proteomic approach to determine whether OSAHS alters protein profiles of serum extracellular microvesicles (SEMVs) and how CIH contributes to such alterations.METHODS:Tandem mass tag (TMT)-labeled quantitative proteomics assay was used to compare the differentially expressed proteins (DEPs) in SEMVs of OSAHS patients and non-OSAHS subjects. To evaluate the contribution of CIH to OSAHS, CIH rodent model was constructed and the same comparative proteomics study was performed in SEMVs from CIH and normoxia rats. The similarity and disparity of DEPs and DEPs-related functions predicted by bioinformatics tools were compared in above-mentioned two models, and several DEPs were selected and further verified by ELISA or Western blotting.RESULTS:TMT-labeled quantitative proteomics assay unravels 32 DEPs in OSAHS patient SEMVs from a total of 560 human SEMV proteins identified. Four DEPs, namely C-reactive protein (CRP), Haptoglobin (HP),Fibronectin (FN1) and Platelet factor 4 (PF4), were further verified by ELISA and three of them (CRP, FN1 and Hp) showed significant difference in expression level between OSAHS and non-OSAHS groups. In SEMVs of rat CIH model, 121 DEPs out of 723 proteins were identified. By comparing the DEPs identified from the two models, 3 proteins (CRP and FN1 and F13a1) were found identical with the same alteration pattern (CRP was upregulated, FN1 and F13a1 were downregulated) in SEMVs from OSAHS patients and CIH rats, which were further verified by Western blotting. Computational functional analysis further revealed the common and distinct DEP-involved pathways under OSAHS or CIH status.CONCLUSIONS:This study provides the first evidence that OSAHS causes significant alteration in SEMV protein composition, which may contribute to OSAHS-triggered multiple organ injury and organ-to-organ communication. Moreover, we have demonstrated that CIH is the primary contributor for increased inflammatory protein expression in SEMV. As CRP is being increasingly recognized not only as a marker but also a mediator of inflammatory response to tissue injury, increased SEMV CRP in CIH/OSAHS may play an important role in OSAHS-induced tissue injury, suggesting SEMV CRP might be a therapeutic target against OSAHS-related complications.

To study the clinical characteristics of autoimmune rheumatic disease-related organizing pneumonia (AIRD-OP), the clinical presentation, radiological findings, treatment, and outcome of AIRD-OP patients were analyzed, in comparison with patients with cryptogenic organizing pneumonia (COP). A total of 131 OP patients were identified, including 57 cases of AIRD-OP, 35 cases of COP, and 39 cases of other disease-related OPs. Among AIRD-OP patients, 36 (63%) presented the symptoms of OP at onset. The primary disease of AIRDs included Sjogren's syndrome (38%), polymyositis/dermatomyositis (23%), rheumatoid arthritis (23%), and undifferentiated AIRD. Compared with COP patients, the prevalence of patients having cough and malaise at baseline was significantly lower (54.4 vs 82.9%, P < 0.05; 49.1 vs 70.6%, P < 0.05), and the signs of moist rales and crackles were more common in AIRD-OP patients (54.4 vs 32.4%, P < 0.05; 49.1 vs 26.5%, P < 0.05). Lung function (TLC%, FVC%) was more significantly reduced in AIRD-OP patients (72 vs 97%, P < 0.05;75 vs 96%, P < 0.05). The dosage of corticosteroids prescribed was significantly higher in AIRD-OP patients (44 vs 37 mg/day, P < 0.05). The complete recovery rate was slightly lower in AIRD-OP patients (22.2 vs 29%, P > 0.05) with a tendency towards higher recurrence rate in AIRD-OP patients (32.7 vs 14.3%, P < 0.05). AIRD-OP may be the most common cause of OP. OP can be the initial presentation of AIRD. Compared with COP patients, AIRD-OP patients are characterized with occult onset but more severe lung involvement and higher recurrence rate.

Activation of cannabinoid receptor type 2 has been shown to have anti-fibrosis function in skin and heart. However, whether activating cannabinoid receptor type 2 inhibits pulmonary fibrosis remains elusive. Lung fibroblasts and TGF-β1 are key players in the pathogenesis of pulmonary fibrosis. In this research, we aimed to investigate the role of cannabinoid receptor type 2 in pulmonary fibrosis in vitro and in vivo. In lung fibroblasts stimulated by TGF-β1, preincubated by cannabinoid receptor type 2 agonist JWH133 not only reduced the elevated levels of collagen I and α-SMA, but also inhibited fibroblasts' proliferation and migration. The dosage of JWH133 had no clear cytotoxic activity, and all these JWH133 effects were partially abrogated by cannabinoid receptor type 2 antagonist SR144528. In bleomycin-induced mice pulmonary fibrosis model, CT images of the lung tissue revealed an extensive ground-glass opacity, reticular pattern and fibrosis stranding. Notably, JWH133 treatment controlled the ongoing fibrotic process (showed by decreased lung density and fibrosis score). Meanwhile, lung histological results revealed that JWH133 treatment suppressed both the inflammatory response and extracellular collagen deposition. SR144528 may increase the pulmonary fibrosis, but no statistically significant difference was proved. Importantly, JWH133 reduced serum profibrotic cytokines levels of TGF-β1 and inhibited TGF-β1/Smad2 pathway in vitro and in vivo. Our research indicated that activating cannabinoid receptor type 2 by a pharmacological method might be a potential strategy for pulmonary fibrosis.

Severe obstructive sleep apnea (OSA) is a risk factor for mortality. The ability of continuous positive airway pressure (CPAP) therapy to mitigate this increased risk of death has not been studied in Chinese adults. The objective of our study was to compare mortality in Chinese patients with simple snoring, untreated OSA, and OSA treated with CPAP.

The prevalence of primary open-angle glaucoma (POAG) increases in obstructive sleep apnea syndrome (OSAS). OSAS could increase cerebrospinal fluid pressure (CSFP) and binocular papilledema.

The aim of this study was to investigate the relationship between nasal structure and olfactory function in patients with obstructive sleep apnea (OSA). Olfaction and nasal structure of 76 adults with OSA diagnosed by polysomnography were measured using acoustic rhinometry and the Sniffin, Sticks (SS) smell test at Anzhen Hospital, a major academic center in Beijing, China. We tested the hypothesis that nasal structure in these patients would correlate with objectively measured olfactory performance. Minimum cross-sectional area (MCA) of the nose was significantly correlated with SS composite score (r = 0.434, p < 0.001), a result that was driven by two of the test's three components: olfactory threshold (OT) (r = 0.385, p = 0.001) and olfactory discrimination (OD) (r = 0.370, p = 0.001) but not olfactory identification (OI) (p > 0.05). Additionally, nasal volume (NV) was associated with composite SS score (r = 0.350, p = 0.002), a finding driven by OT (r = 0.283, p = 0.014). These data suggest that nasal structure affects parameters of olfactory function, likely via alterations in nasal airflow. Thus, anatomic abnormalities and diseases involving airflow (such as OSA) may cause, in part, olfactory dysfunction that is amenable to treatment. We speculate that surgery that alters nasal volume and MCA may improve olfactory performance.

Objective To study the proliferation and apoptosis of related proteins in pathological liver tissues of alcohol-induced mice,and establish a model and time-evolution rule of liver cell apoptosis,which can be used to guide the clinical treatment of acute alcoholic liver injury.Methods A total of 30 male KM mice were fed in a clean grade animal room at the Capital Medical University and then randomly (random number) separated into two groups.The 10 mice in the normal group were fed without ethanol,while the other 20 mice in the experimental group were given a one-time grant of 50％ ethanol (12 mL/kg) by gavage.The mice in the experimental group were killed at two time points,6 h for 10 mice and 12 h for the other 10,after the intragastric administration.Hematoxylin and eosin (HE) staining was used to observe the morphological changes of liver in mice.The concentrations of T-ERK,p-ERK,PKC,p-PKC and caspase-3 were determined by the Western-blot method.The data were analyzed by Analysis of variance (ANOVA) method using statistical software SPSS 11.5 and criterion P ＜ 0.05 is chosen to determine differences that are statistically significant.Results By observing the behavioral changes and morphological indexes of mice,we confirmed the success of the model for acute alcoholic liver injury.During the process of re-building the model,no mice died.The mice in the experimental group appeared in drunken states,such as sleepiness and slowness of movement.Compared to the normal group,the experimental subgroup at the 6 h point showed no difference statistical significant; while the experimental subgroup at the 12 h point showed obvious histological changes in tissues,including the disorder of hepatic lobule structure and fatty vacuolization of hepatocytes.At the same time,in the experimental subgroup at the 12 h point,both P-ERK and P-PKC significantly decreased [(2.41 ±0.38),(0.97 ±0.25),F=4.82,P＜0.05; (0.16 ±0.00),(0.08 ± 0.01),F =29.63,P ＜ 0.05],but caspase-3 significantly increased [(0.30 ± 0.02),(0.11 ± 0.01),F =34.38,P ＜ 0.05].Conclusions In mice after intragastric administration of large doses of alcohol,the hepatic cell apoptosis appeared mainly after 6 h but before 12 h,therefore 6 ～ 12 h might be the time window to inhibit the cell apoptosis of mice' s acute liver injury from alcohol induction.