Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions.

BACKGROUND AND OBJECTIVE: Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients. METHODS: A total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro. RESULTS: Endothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05). CONCLUSION: NP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020.

BACKGROUND: The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation. METHODS: A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups. RESULTS: Eosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score-matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0-12.5) vs. 5.0 (4.0-6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753-27,404) vs. 9,109(6,402-12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days. CONCLUSION: Eosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Epithelial CST1 Promotes Airway Eosinophilic Inflammation in Asthma via the AKT Signaling Pathway.

PURPOSE: Epithelial cystatin SN (CST1), a type 2 cysteine protease inhibitor, was significantly upregulated in asthma. In this study, we aimed to investigate the potential role and mechanism of CST1 in eosinophilic inflammation in asthma. METHODS: Bioinformatics analysis on Gene Expression Omnibus datasets were used to explore the expression of CST1 in asthma. Sputum samples were collected from 76 asthmatics and 22 control subjects. CST1 mRNA and protein expression in the induced sputum were measured by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. The possible function of CST1 was explored in ovalbumin (OVA)-induced eosinophilic asthma. Transcriptome sequencing (RNA-seq) was used to predict the possible regulated mechanism of CST1 in bronchial epithelial cells. Overexpression or knockdown of CST1 was further used to verify potential mechanisms in bronchial epithelial cells. RESULTS: CST1 expression was significantly increased in the epithelial cells and induced sputum of asthma. Increased CST1 was significantly associated with eosinophilic indicators and T helper cytokines. CST1 aggravated airway eosinophilic inflammation in the OVA-induced asthma model. In addition, overexpression of CST1 significantly enhanced the phosphorylation of AKT and the expression of serpin peptidase inhibitor, clade B, member 2 (SERPINB2), while knockdown using anti-CST1 siRNA reversed the trend. Furthermore, AKT had a positive effect on SERPINB2 expression. CONCLUSIONS: Increased sputum CST1 may play a key role in the pathogenesis of asthma through involvement in eosinophilic and type 2 inflammation through activation of the AKT signaling pathway, further promoting SERPINB2 expression. Therefore, targeting CST1 might be of therapeutic value in treating asthma with severe and eosinophilic phenotypes.

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma.

INTRODUCTION: CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported. OBJECTIVE: We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications. METHODS: The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored. RESULTS: The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function. CONCLUSIONS: Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.

Spatial-Temporal Distribution Variation of Ground-Level Ozone in China's Pearl River Delta Metropolitan Region.

Long-term exposure to ozone pollution will cause severe threats to residents' physical and mental health. Ground-level ozone is the most severe air pollutant in China's Pearl River Delta Metropolitan Region (PRD). It is of great significance to accurately reveal the spatial-temporal distribution characteristics of ozone pollution exposure patterns. We used the daily maximum 8-h ozone concentration data from PRD's 55 air quality monitoring stations in 2015 as input data. We used six models of STK and ordinary kriging (OK) for the simulation of ozone concentration. Then we chose a better ozone pollution prediction model to reveal the ozone exposure characteristics of the PRD in 2015. The results show that the Bilonick model (BM) model had the highest simulation precision for ozone in the six models for spatial-temporal kriging (STK) interpolation, and the STK model's simulation prediction results are significantly better than the OK model. The annual average ozone concentrations in the PRD during 2015 showed a high spatial variation in the north and east and low in the south and west. Ozone concentrations were relatively high in summer and autumn and low in winter and spring. The center of gravity of ozone concentrations tended to migrate to the north and west before moving to the south and then finally migrating to the east. The ozone's spatial autocorrelation was significant and showed a significant positive correlation, mainly showing high-high clustering and low-low clustering. The type of clustering undergoes temporal migration and conversion over the four seasons, with spatial autocorrelation during winter the most significant.

[Effect of Electroacupuncture Stimulation of Sensitized Acupoints on Bowel Dysfunction in Rats with Diarrhea-predominant Irritable Bowel Syndrome].

OBJECTIVE: To investigate the effect of electroacupuncture(EA)stimulation of sensitized acupoints on bowel dysfunction in diarrhea-predominant irritable bowel syndrome(D-IBS)rats. METHODS: Fifty SD rats were randomly divided into control, model, EA sensitized acupoint and EA non-sensitized acupoint groups, with 20 rats in the model group and 10 rats in each of the other 3 groups. The D-IBS model was established by chronic restraint stress and intragastric administration of folium sennae (0.3 g/mL, 10 mL/kg), once daily for 2 weeks, followed by two weeks' restraint stress stimulation. The sensitized acupoints were determined by locating the extravasation points of Evans Blue (EB) dye after tail-intravenous injection, and stimulated with EA (2 mA, 2 Hz) for 30 min, once daily for 7 consecutive days. For rats of the EA non-sensitized acupoint group, bilateral BL 15 were stimulated with the same parameters and same stimulation duration. The rats' bowel mobility was evaluated by Bristol stool scale (BSS), loose stools rate and diarrhea index. RESULTS: After modeling, the BSS, loose stool rate, and diarrhea index were significantly increased in the model group relevant to the control group (P<0.05). After the treatment, the BSS, loose stool rate, and diarrhea index on day 7 were considerably lowered in the EA-BL 25 group (P<0.05) but not in EA-BL15 group (P<0.05), suggesting a better therapeutic effect of EA of the sensitized acupoint. No significant changes were found in the abovementioned 3 indexes on day 4 after the treatment relevant to the model group (P<0.05). CONCLUSIONS: EA stimulation of the sensitized acupoint can improve diarrhea in D-IBS rats.