Objective To explore the effects of dioscin (Dio) on airway inflammation and microRNA-155 (miR-155)/cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathways in asthmatic mice. Methods Seventy mice were randomly divided into control group, model group, inhibitor negative control group (inhibitor-NC group), miR-155 inhibitor group, and Dio group, Dio+miR-155 mimic negative control group (Dio+mimic-NC group), Dio+miR-155 mimic group, with 10 mice in each group. Using house dust mite to induce the preparation of asthma mouse models; enzyme linked immunosorbent assay was used to detect the levels of PGE2, tumor necrosis factor α (TNF-α), cysteyl leukotrienes (CysLTs), cysteyl leukotriene receptor 1 (CysLTR1) and interleukin (IL)-4, IL-5, IL-13 in mouse bronchoalveolar lavage fluid (BALF); hematoxylin-eosin and periodic acid-Schiff staining were used to observe the infiltration of inflammatory cells around the airway and the secretion of mucus by goblet cells; quantitative real-time PCR was used to detect the expression levels of miR-155 and COX-2 mRNA in mouse lung tissue; Western blot was used detect the expression of COX-2 protein in mouse lung tissue. Results MiR-155 inhibitor and Dio could reduce the levels of PGE2, TNF-α, CysLTs, CysLTR1 and IL-4, IL-5, IL-13 in BALF of asthmatic mice, reduce lung tissue inflammatory cell infiltration and goblet cell mucus secretion, and reduce lung tissue miR-155, COX-2 mRNA and protein expression; and miR-155 mimic could significantly weaken the anti-asthma effect of Dio. Conclusion The anti-asthma effect of Dio may be related to the inhibition of miR-155/COX-2/PGE2 pathway to reduce airway inflammation in asthmatic mice.
Objective To investigate the clinical characteristics of upper airway cough syndrome ( UACS) and the relationship of UACS with upper airway diseases, cough variant asthma ( CVA) , and gastroesophageal reflux disease ( GERD) . Methods 92 subjects with chronic cough and throat symptoms and signs were included in the study. The medical records were collected fromall subjects, and 49 subjects suspected for CVA undertook bronchial provocation test. Then the efficacy was evaluated and etiology were analyzed based on the efficacy of targeted treatment. Results Bronchial provocation test yielded positive results in 14 subjects suspected of CVA, accounting for 15. 2% of all cases ( 14/92) . 18. 5% ( 17 /92) of patients had a history of chronic gastritis or combined symptoms of GERD, of whom anti-gastroesophagealreflux treatment was effective. The patients with rhinitis, sinusitis history and/ or symptoms accounted for 33. 7% of cases ( 31 cases) . 51. 1% ( 47/92) of patients had only signs and symptoms of chronic pharyngitis. Conclusions UACS is not only due to the rhinitis and/ or sinusitis but also chronic pharyngitis. Chronic pharyngitis may be secondary to chronic rhinitis/ sinusitis with post nasal drip and gastroesophageal reflux, also may be an independent cause of chronic cough.
Objective To reveal the differences in gene expression levels between Th2-driven classical asthma (CA) and Th2-driven cough variant asthma (CVA) in order to investigate the pathogenesis of asthma further. Methods Clinical data were collected from asthmatic patients in the Department of Respiratory and Critical Care of Sichuan Provincial People's Hospital from June 1, 2018, to December 31, 2019. The healthy control (HC) group was healthy adults from the physical examination center. Gene expression of peripheral blood mononuclear cells (PBMCs) in the CA group, CVA group, and HC group was determined by full-length transcriptome sequencing. Differential genes were screened by GO, KEGG analysis, and protein-protein interaction (PPI) network analysis. The results of interaction network analysis were visualized by Cytoscape. Finally, the candidate genes were verified by real-time quantitative polymerase chain reaction (RT-PCR). ResultsA total of 31 patients with asthma were included in the study, including 20 patients in the CA group and 11 patients in the CVA group. According to serum total IgE > 60 IU/mL and fractional exhaled nitric oxide (FeNO) > 40 ppb as the screening condition, 9 cases of Th2-driven CA and 5 cases of Th2-driven CVA were screened for analysis. Gene expression analysis showed 300 differentially expressed genes between the Th2-driven CA group and the Th2-driven CVA group, among which 155 genes were up-regulated, and 145 were down-regulated. GO enrichment analysis showed that differential genes were mainly enriched in drug response, nitrogen compound biosynthesis, cytoplasmic matrix, protein binding, ATP binding, etc. KEGG pathway analysis showed that differential genes were mainly concentrated in 2-oxy-carboxylic acid metabolism and cytotoxic signaling pathways mediated by natural killer cells. PPI analysis revealed extensive protein interactions between different genes. Ten candidate genes were screened for RT-PCR verification and finally found that CLU, GZMB, PPBP, PRF1, PTGS1, and TMSB4X were significantly differentially expressed between the Th2-driven CA group and the Th2-driven CVA group. Conclusions Asthma's occurrence results from the interaction of many genes and pathways. CLU, GZMB, PPBP, PRF1, PTGS1, and TMSB4X genes may be essential in developing Th2-driven CVA to Th2-driven CA.
Objective
To systematically evaluate the effectiveness and safety of mepolizumab in treating eosinophilic asthma.
Methods
Databases including PubMed, Embase, ISI Web of Science, Cochrane CENTRAL, MEDLINE, VIP and CNKI were searched to collect randomized controlled trials (RCTs) about mepolizumab for eosinophilic asthma from inception to October 2016. The references of these articles and relevant conference information were also manually retrieved. Meta-analysis was performed by RevMan 5.1 software after two researchers independently selected the literatures, extracted data and evaluated the quality according to the inclusion and exclusion criteria.
Results
A total of 9 RCTs involving 2273 patients were included. Compared with the control group, the acute exacerbation rate of asthma was decreased significantly in the mepolizumab treatment group [RR=0.67, 95%CI (0.53, 0.85), P=0.0009], eosinophil count in blood was significantly reduced [MD=–0.22, 95%CI (–0.29, –0.15), P<0.00001], eosinophil count in sputum was also significantly reduced [MD=–6.37, 95%CI (–9.68, –3.06), P<0.0002], and the proportion of patients with increased asthma-related quality of life (ACQ) score was higher significantly. The overall incidence of adverse reactions was similar between two groups [RR=0.90, 95%CI (0.71, 1.14), P=0.39]. The incidence of serious adverse reactions of mepolizumab treatment was superior to that of placebo [RR=0.45, 95%CI (0.23, 0.89), P=0.02]. The overall incidence of cardiovascular events was comparable between placebo and mepolizumab treatment [RR=0.95, 95%CI(0.40, 2.22), P=0.90]. Mepolizumab treatment may have a role in improving lung function, but the effect was not obvious.
Conclusion
Mepolizumab treatment can reduce the number of eosinophils in blood and sputum, reduce the exacerbation rate, and improve the quality of life of asthmatic patients with better safety.
ObjectiveTo systematically review the effects of aminophylline combined with traditional Chinese medicine (TCM) in the treatment of asthma.
MethodsDatabases including The Cochrane Library(Issue 1, 2015), PubMed, EMbase, CNKI, VIP and WanFang Data databases were electronically searched from January 2005 to December 2014 to collect randomized controlled trials (RCTs) about the treatment of bronchial asthma combining aminophylline with TCM. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.
ResultsA total of 10 RCTs involving 820 participants were included. The results of meta-analysis showed that: The total clinical effective rate in the aminophylline plus TCM group was higher than that of the aminophylline alone group (RR=1.22, 95%CI 1.11 to 1.33). The FEV1 in the aminophylline plus TCM group was also higher than that of the aminophylline alone group (MD=0.53, 95%CI 0.33 to 0.73).
ConclusionCurrent evidence shows, the total clinical effective rate of aminophylline combined with TCM for asthma is better than that of aminophylline alone, and its mechanism may be related to the improvement of FEV1. Due to the limited quantity and quality of included studies, the above conclusion needs to be further verified by more high quality studies.
Objective
To observe the level of vitamin D in patients with steroid resistant (SR) asthma, and investigate the effect of 1,25-(OH)2D3 on JNK/AP-1 and glucocorticoid receptor of T lymphocytes in SR asthmatics.
Methods
Sixty-two outpatients and inpatients with asthma with acute exacerbation between 2014 and 2015 were recruited in the study, including 26 cases of steroid sensitive (SS) asthmatics and 36 cases of SR asthmatics. Meanwhile 25 healthy volunteers were recruited as control. Clinical data were collected and peripheral venous blood was sampled for measuring the level of 25-(OH)D and separating the T lymphocytes. T lymphocytes were assigned to six groups, ie. a healthy control group (Group A), a SS asthmatics control group (Group B), a SR asthmatics control group (Group C), a SR asthmatics with JNK inhibitor (SP600125)+1,25-(OH)2D3 group (Group D), a SR asthmatics with JNK inhibitor (SP600125) group (Group E), and a SR asthmatics with 1,25-(OH)2D3 group (Group F). T lymphocytes were cultured for 48 hours. By the end of culture, the expression of phospho-JNK (p-JNK) and phospho-glucocorticoid receptor (p-GR) of T lymphocytes were detected by Western blot method, and the expression of c-Jun mRNA was detected by RT-PCR method.
Results
The level of 25-(OH) D was lower in Group B and Group C than Group A (P<0.05), and lower in Group C than Group B (P<0.05). The level of p-JNK was higher in Group B and Group C than Group A (P<0.05), higher in Group C than Group B (P<0.05), lower in Group E and Group F than Group C (P<0.05), lower in Group D than Group F (P<0.05). The level of p-GR was lower in Group C than Group A and Group B (P<0.05), higher in Group E and Group F than Group C (P<0.05), higher in Group D than Group F (P<0.05). The level of c-Jun mRNA was higher in Group B and Group C than Group A (P<0.05), higher in Group C than Group B (P<0.05), lower in Group E and Group F than Group C (P<0.05), and lower in Group D than Group F (P<0.05). The 25-(OH) D level was negatively correlated with the expression of p-JNK and c-Jun mRNA in Group C (r=–0.69, r=–0.65, P<0.05). However, there was a positive correlation between the 25-(OH) D level and p-GR (r=0.72, P<0.05).
Conclusions
There is a high prevalence of vitamin D deficiency or lack in SR asthmatics. 1,25-(OH)2D3 can promote the expression of p-GR by inhibiting the JNK/AP-1 signaling pathway of T lymphocytes in SR asthmatics, which may be one of the mechanisms of vitamin D to improve glucocorticoid resistance in SR asthmatics.
ObjectiveTo survey the current asthma impact on quality of life and related factors in China.
MethodsTwo thousand and thirty-four asthmatic patients, from bronchial asthma prevalence epidemiology survey in the population over 14 years old in 8 areas of China from 2009 to 2013, were enrolled. The data about medical resource use, control status and quality of life were collected by detailed questionnaire and analysed using the Epidata database and SAS 9.2 software.
ResultsOut of the 2034 asthma patients, 1213 patients (59.6%) reported that their activities including entertainment, learning, fertility and employment were limited due to asthma. In the four aspects of entertainment, education, family and employment, 688 patients (33.8%) had one limited activity in one aspect, 165 patients (8.19%) had most of activities limited in one aspect, 246 patients (12.1%) had limited activities in two or three aspects, 114 patients (5.6%) had limited activities in all aspects. One hundred and eighty-one patients (8.9%) needed help in daily life, such as cooking, shopping, doing housework. Seventy-one patients (3.5%) even needed help in eating, personal hygiene, toilet, and their daily activities were remarkably restricted. Eighty-one patients (4.0%) had motive of suicide. Aging, comorbidity, and medication use were the most important factors.
ConclusionAsthma has a significant negative effects on the life and emotion of patients, and proper control of comorbidity and regular treatment of asthma are effective ways to improve the life and emotional state of patients with asthma.
ObjectiveTo explored the influence of disease changes, weight gain, eosinophil levels and other factor in pregnancy women with asthma. MethodsCase records of gestational asthma patients produced in the obstetrics department of Peking University People's Hospital from October 2010 to October 2020 were collected, and refer to electronic medical records of clinics (pre-pregnancy and pregnancy). According to the disease control (asthma related unplanned respiratory clinics, emergency or hospitalization), patients were divided into pregnancy stable group and pregnancy fluctuation group. The basic characteristics, pre-pregnancy asthma control, weight gain during pregnancy and peripheral blood eosinophil level before labor were retrospectively analyzed. The cause of asthma attacks, clinical characteristics and distribution of gestational time in pregnancy fluctuations were described. Peripheral blood eosinophil levels in different period during pregnancy in the stable group were analyzed. ResultsTotally 124 cases of natural pregnancy singleton were enrolled in the study. The age was (32.3±3.9) years old. There were 71 patients in stable group and 53 patients in fluctuation group. The proportion of pre-pregnancy instability in the fluctuating pregnancy group was higher than that in the stable pregnancy group (P<0.05). The proportion of intermittent medication before pregnancy was higher in the fluctuating pregnancy group than in the stable pregnancy group (P<0.05). Peripheral blood eosinophil count before labor and the number of cases with eosinophil count≥0.15×109/L before labor were higher in the fluctuation group (all P<0.05). The proportion of hypertentive diseases in pregnancy and fetal distress in uterus were higher in the fluctuation group (all P<0.05). The common cold was the common trigger factor (38.2%) and asthma recurrences occur between 13 and 36 weeks of gestation (65.8%) in fluctuation group. In further analysis of subgroup (the stable group), peripheral blood eosinophil count in early pregnancy (P<0.05) and pregnant metaphase (P<0.05) were higher than before delivery. The number of cases with eosinophil count>0.15×109/L in pregnant metaphase (P<0.05) was higher than before delivery. ConclusionsAsthma fluctuates during pregnancy is associated with adverse maternal and fetal outcomes. It is very important and critical that asthma control before pregnancy, weight gain management and eosinophil level monitoring of patients with asthma during pregnancy. The whole management is imperative in women with asthma during pregnancy.
Objective To explore the relationship between nasopharyngeal microecology and diseases in children with bronchial asthma. Methods A total of 41 children with asthma who were treated in Hainan Provincial Hospital of Traditional Chinese Medicine between November 2020 and March 2023 were retrospectively included in the study, and 26 healthy children undergoing adenoid examination in the same period were selected as the control group. Samples of nasal mucosa were collected from the anterior and medial side of inferior turbinate, and the expression of DEFB2, IL17A, TSLP, IL13, IL5 and T1R3 genes was analyzed by polymerase chain reaction. Nasal swabs were collected from the children, and the bacterial composition was analyzed by 16S ribosomal RNA gene sequencing. Results Compared with the control group, the rate of atopy cases in the asthma group increased significantly (53.7% vs. 19.2%, P<0.05). At the phylum level, compared with the control group, the phylum Chloroflexi, the phylum Patescibacteria, the phylum Tenericutes and the phylum Nitrospirae in the asthma group increased significantly (P<0.05), and the phylum Elusimicrobia decreased significantly (P<0.05). At the genus level, compared with the control group, the members of Bacillus (Fimnicutes), Ruminococcus (Fimnicutes), Rhodococcus (Actinobacteria), Acinetobacter (Proteobacteria), Moraxella (Proteobacteria) and Asaia (Proteobacteria) in the asthma group increased significantly (P<0.05), and the members of Enterococcus (Fimnicutes), Alkanindiges (Proteobacteria), Rickettsia (Proteobacteria), and Rhizobium (Proteobacteria) in the asthma group decreased significantly (P<0.05). Compared with the control group, the Shannon index of the asthma group decreased significantly (2.63±1.45 vs. 3.90±1.44; t=2.708, P=0.010). According to receiver operating characteristic curve analysis, the optimal cut-off point of Shannon index was 3.10. In all study populations, compared with children whose Shannon index was higher than the cut-off point, children whose Shannon index was lower than the cut-off point were characterized by increased expression of IL17A and T1R3 (P<0.05) and decreased expression of TSLP (P<0.05). Conclusion The composition and abundance of nasopharyngeal microbiota are significantly different between children with asthma and healthy control children.
Objective To explore the clinical and inflammatory characteristics and risk factors of severe asthma to improve clinicians' awareness of the disease. Methods The general information of patients with asthma who visited the Department of Respiratory Medicine, the First Hospital of Shanxi Medical University from May 2018 to May 2021, as well as the diagnosis and treatment of asthma, personal history, comorbidities, auxiliary examination, asthma control test (ACT) score were collected. A total of 127 patients were included, including 40 in the severe asthma group and 87 in the mild-to-moderate asthma group. Chi-square test, independent sample t test and logistic regression were used to analyze the clinical characteristics, inflammatory markers and risk factors of severe asthma. Results Compared with the patients with mild to moderate asthma, the patients with severe asthma were more older (51.0±12.0 years vs 40.7±12.8 years, P<0.05), had more smokers (32.5% vs. 14.9%, P<0.05), and more males (67.5% vs. 40.2%, P<0.05). The patients with severe asthma got poor FEV1%pred [(56.1±23.8)% vs. (93.2±18.0)%, P<0.05] and FEV1/FVC [(56.7±13.2)% vs. (75.8±9.0)%, P<0.05)], and more exacerbations in the previous year (2.7±3.1 vs. 0.1±0.4, P<0.05), lower ACT score (14.4±3.7 vs. 18.0±5.0, P<0.05), and higher blood and induced sputum eosinophil counts [(0.54±0.44)×109/L vs. (0.27±0.32)×109/L, P<0.05; (25.9±24.2)% vs. (9.8±17.5)%, P<0.05]. There was no significant difference in the proportion of neutrophils in the induced sputum or FeNO between the two groups (P>0.05). Analysis of related risk factors showed that smoking (OR=2.740, 95%CI 1.053 - 7.130), combined with allergic rhinitis (OR=14.388, 95%CI 1.486 - 139.296) and gastroesophageal reflux (OR=2.514, 95%CI 1.105 - 5.724) were risk factors for severe asthma. Conclusions Compared with patients with mild to moderate asthma, patients with severe asthma are characterized by poor lung function, more exacerbations, and a dominant eosinophil inflammatory phenotype, which is still poorly controlled even with higher level of treatment. Risk factors include smoking, allergic rhinitis, and gastroesophageal reflux, etc.
