Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty.

Background: Ambroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance. Methods: This study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population. Results: Between 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: -0.29; 95% CI: -0.53 to -0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: -0.18; 95% CI: -0.34 to -0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported. Discussion: In hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

Role of miR-584-5p in Lipopolysaccharide-Stimulated Human Bronchial Epithelial Cell Inflammation and Apoptosis.

Acute lung injury (ALI)/acute respiratory distress syndrome is a common clinical syndrome characterized by respiratory failure. MicroRNAs (miRNAs) are closely related to ALI and acute respiratory distress syndrome. TargetScan software analysis showed that miR-584-5p can bind to the 3' noncoding region of TLR4, which is involved in the occurrence and development of ALI, thereby affecting the inflammatory pathway and inflammation development. Thus, we aimed to determine whether miR-584-5p affects ALI. Human bronchial epithelial (16-HBE) cells were transfected with miR-584-5p mimics or inhibitors and then stimulated with lipopolysaccharide (LPS).The cell viability, apoptosis, release of proinflammatory factors, mTOR, and NF-κB pathway protein expression were evaluated respectively. Mimic584 increased, whereas inhibitor584 decreased, LPS-stimulated inflammation. The protein expression of inflammatory factors was significantly increased in 16-HBE cells in the mimic584 + LPS group and decreased in the inhibitor584 + LPS group. Mimic584 activated mTOR and the NF-κB-related proteins P65 and p-p65, whereas inhibitor584 inactivated the proteins in 16-HBE cells. Overexpression of miR-584 significantly promoted apoptosis in LPS-stimulated 16-HBE cells. There were no differences in the proliferation and cell cycle of LPS-stimulated 16-HBE cells regardless of mimic584 or inhibitor584 transfection. Collectively, we demonstrated that inhibitor584 can alleviate ALI-induced expression of inflammatory factors via mTOR signaling and the NF-κB pathway. In conclusion, we found that inhibitor584 transfection could be a potential therapeutic strategy for ALI.

Clinical Characteristics of Patients with Pulmonary Thromboembolism Based on Computer Statistical Analysis.

In order to explore the reliable clinical characteristics of patients with pulmonary thromboembolism, this paper applies computer statistical analysis methods to the analysis of clinical characteristics of patients with pulmonary thromboembolism. Moreover, starting from the actual situation, this paper combines experiments to study the case, uses sample screening and sample processing to group samples freely, and conducts grouping reliability research through data statistics methods. After verifying the reliability of the grouping, this paper combines the samples to test the effectiveness of the computer statistical analysis method applied to the clinical characteristic analysis of patients with pulmonary thromboembolism and conducts numerical analysis in combination with the comparative analysis method. The results of the research show that the computer statistical method proposed in this paper has a good effect on the clinical characteristics of patients with pulmonary thromboembolism and meets the actual needs of clinical analysis.

Combined CT score, blood mononuclear cell count, LDH, and plasma D-dimer for viral pneumonia diagnosis: a retrospective study.

OBJECTIVE: Due to a continued increase in viral pneumonia incidence and resulting high mortality, fast and accurate diagnosis is important for effective management. This investigation examined the significance of blood biomarkers and the CT score in the early diagnosis of viral pneumonia. METHODS: Patients who were hospitalized due to radiologically-confirmed pneumonia and underwent virus antigen rapid test were enrolled. Their clinical information was compared. Blood mononuclear cell count, LDH, and plasma D-dimer were obtained. To evaluate the utility of biomarker levels in differentiating viral pneumonia from other pneumonia, ROC curves were developed to analyze the AUC. The optimal cut-off thresholds, specificity, sensitivity, and predictive values were assessed using the Youden index. The added value of the multi-marker approach was delineated using IDI and Reclassification analyses using NRI; IDI and NRI values were examined with 95% CI. RESULTS: Overall, 1163 inpatients were recruited between January 2017 and January 2021. They were sub-divided into the viral pneumonia (n = 563) and non-viral pneumonia (n = 600) categories. We found that the CT score, blood mononuclear cell count, LDH, and plasma D-dimer were markedly elevated in viral pneumonia patients. At an LDH threshold of 693.595 U/L, an AUC of ROC was 0.805 in differentiating viral pneumonia. The combination of CT score and blood biomarkers had an ROC AUC value of 0.908. CONCLUSIONS: Combining elevated biomarkers with CT assessments outperformed the CT score alone in identifying viral pneumonia. It is crucial to better characterize the significance of biomarkers in combination with CT assessments in the diagnosis of viral pneumonia.

Application of weighted gene co-expression network analysis to identify the hub genes in H1N1.

OBJECTIVE: Identifying the disease-associated interactions between different genes helps us to find novel therapeutic targets and predictive biomarkers. METHODS: Gene expression data GSE82050 from H1N1 and control human samples were acquired from the NCBI GEO database. Highly co-expressed genes were grouped into modules. Through Person's correlation coefficient calculation between the module and clinical phenotype, notable modules were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted, and the hub genes within the module of interest were identified. Also, gene expression data GSE27131 were acquired from the GEO database to verify differential key gene expression analysis. The CIBERSORT was used to evaluate the immune cells infiltration and the GSVA was performed to identify the differentially regulated pathways in H1N1. The receiver operating characteristic (ROC) curves were used to assess the diagnostic values of the hub genes. RESULT: The black module was shown to have the highest correlation with the clinical phenotype, mainly functioning in the signaling pathways such as the mitochondrial inner membrane, DNA conformation change, DNA repair, and cell cycle phase transition. Through analysis of the black module, we found 5 genes that were highly correlated with the H1N1 phenotype. The H1N1 project from GSE27131 confirmed an increased expression of these genes. CONCLUSION: By using the WGCNA we analyzed and predicted the key genes in H1N1. BRCA1, CDC20, MAD2L1, MCM2, and UBE2C were found to be the most relevant genes, which may be therapeutic targets and predictive biomarkers for H1N1 therapy.

HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

[Comparison of relevant indicators of coagulation and fibrinolysis in patients with varying severity of community-acquired pneumonia].

OBJECTIVE: To compare the relevant indicators of coagulation and fibrinolysis in patients with varying severity of community-acquired pneumonia (CAP). METHODS: A total of 107 CAP hospitalized patients at Department of Respiratory Medicine, Affiliated Hospital, Chengde Medical College from July 2013 to June 2014 were enrolled as pneumonia group while another 52 healthy outpatients served as control group. The levels of routine blood test, coagulation function, procalcitonin and C-reactive protein (CRP) were measured and compared among different groups. All hospitalized CAP patients were divided into low and high-risk groups according to pneumonia severity index (PSI). And all indicators were measured to examine the differences among different groups. RESULTS: The white blood cell count in pneumonia group was significantly higher than that in control group ((9.3 ± 5.1) vs (7.5 ± 2.9) × 10(9)/L, P < 0.05). The red blood cell count, hemoglobin and platelet count in pneumonia group were significantly lower than those in control group ((4.3 ± 0.6) vs (4.8 ± 0.5) × 10(12)/L, (131.1 ± 18.7) vs (144.9 ± 17.4) g/L, (199.3 ± 69.4) vs (237.9 ± 72.5) × 10(9)/L, all P < 0.05). The D-dimer, fibrinogen degradation products (FDPs), fibrinogen (FIB), activated partial thromboplastin time (APTT) and prothrombin time (PT) in pneumonia group were significantly higher than those in control group ((1.86 ± 1.28) vs (0.48 ± 0.38) mg/L, (6.42 ± 3.27) vs (2.17 ± 1.46) mg/L, (3.87 ± 1.17) vs (3.42 ± 0.96) g/L, (35.64 ± 8.34) vs (31.29 ± 11.19) s, (12.21 ± 1.40) vs (11.36 ± 2.19) s, all P < 0.05) while thromboplastin time (TT) was lower than that in control group ((13.43 ± 3.38) vs (16.16 ± 2.89) s, P < 0.05). The levels of D-dimer, FDPs, procalcitonin, CRP, APTT and PT in high-risk group were significantly higher than those in low-risk group ((2.94 ± 1.14) vs (1.16 ± 0.78) mg/L, (8.85 ± 2.82) vs (4.85 ± 2.49) mg/L, (1.72 ± 1.16) vs (0.40 ± 0.51) µg/L, (104.2 ± 61.9) vs (67.4 ± 59.5) mg/L, (38.80 ± 8.41) vs (33.60 ± 7.69) s, (12.64 ± 1.76) vs (11.94 ± 1.03) s, all P < 0.05) while platelet count and TT were lower than those in low-risk group ((172.8 ± 57.1) vs (216.5 ± 71.6) × 10(9)/L, (12.10 ± 2.66) vs (14.28 ± 3.53) s, all P < 0.05). The abnormal rates of procalcitonin, D-dimer and FDPs in high-risk group were significantly higher than those in low-risk group (100% (42/42) vs 86.2% (56/65), 95.2% (40/42) vs 75.4% (49/65), 95.2% (37/42) vs 44.6% (29/65), all P < 0.05). The plasma levels of D-dimer, FDPs, procalcitonin and CRP were well-correlated with index of pneumonia severity (r = 0.636, 0.608, 0.629, 0.250, all P < 0.05). And the plasma level of platelet was negatively correlated with index of pneumonia severity (r = -0.320, P < 0.01). CONCLUSIONS: The red blood cell, hemoglobin and platelets are lower in patients with pneumonia than those in normal subjects. And the patients with pneumonia have coagulation and fibrinolysis disorders. The plasma levels of D-dimer, FDPs, procalcitonin, CRP and platelets are well-correlated with severity of CAP.

[Epidemiologic study on the relationship between smoking and sleep apnea/hypopnea syndrome].

OBJECTIVE: To investigate how smoking was affecting the prevalence of sleep apnea/ hypopnea syndrome (SAHS) among adults aged over 30 years in Chengde city of Hebei province. METHODS: 1168 subjects, over 30 years of age were derived from a random sample from a community-based population in Shuangqiao district of Chengde city. All subjects responded to a questionnaire at their own houses regarding their habits of snoring and smoking. 1168 subjects (95.2%) answered the questions satisfactorily. RESULTS: (1) Among the smoking groups, the prevalence of snoring was 69.09%, higher than that in the nonsmoking groups 45.07% (P = 0.000). (2) In males, the smoking group had a higher prevalence (69.72%) of snoring than in the nonsmoking group (60.80%, P = 0.033). (3) Females in the smoking group had a higher prevalence of snoring (61.80%) than in the nonsmoking group (39.70%, P = 0.011). (4) The prevalence of snoring in males (60.80%) was significantly higher than that in females (39.70%, P = 0.000). (5) The prevalence (69.72%) of snoring in smoking males was similar to that in smoking females (61.80%, P = 0.336). (6) Data from logistic regression analysis indicated that smoking was one of the factors affecting snoring. (7) According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated. According to the AHI > or = 5 and the ESS > or = 9 cutoff-points, the prevalence rates of SAHS in smoking groups were both significantly higher than that in nonsmoking groups (P < 0.001). CONCLUSION: Smoking and snoring among adults aged over 30 years had correlation in our city.