Objective To study the efect of montelukast for improving bronchial hyperresponsiveness (BHR) in treatment of bronchiolitis. Methods Four hundreds infants, 3 to 24 months old, hospitalized with acute bronchiolitis in three Hospitals (Urumqi Children’s Hospital, Pediatrics Department of First Ailiated Hospital of Xinjiang Medical University, and Pediatrics Department of Army General Hospital) from January, 2007 to January, 2008, were randomly assigned into four groups: placebo group (n=92), budesonide group (n=91), montelukast short-course group (7 days, n=88), and montelukast long-course group (28 days, n=90). Main outcome measure was BHR ater treatment, including recurrent bronchiolitis wheezing and asthma incidence rate. Secondary measures were changes in serum T-IgE level and eosinophilic cationic protein (ECP) level. Results All four groups were comparable at baseline. No signiicant diferences were observed between placebo group and budesonide group in changes of serum T-IgE (F=6.17, P=0.00), ECP (F=8.13, P=0.00), recurrent post-bronchiolitis-wheezing (χ2=49.46, P=0.00) and asthma incidence rate (χ2=27.21, P=0.00). Ater treatment with montelukast, there was statistical signiicance in T-IgE and ECP level, times of recurrent bronchiolitis wheezing and asthma incidence rate, as follows, montelukast short-course group versus placebo group (F=12.56, P=0.00), montelukast short-course group versus budesonide group (F=7.22, P=0.00), montelukast long-course group versus placebo group (F=20.48, P=0.00), montelukast long-course group versus budesonide group (F=13.56, P=0.00), montelukast short-course group versus montelukast long-course group (F=1.04, P=0.00). Conclusions Budesonide treatment for 7 days can not improve bronchial hyperresponsiveness induced by bronchiolitis, while montelukast does, that is, montelukast can decrease both the times of bronchiolitis wheezing and asthma incidence rate. Long-course treatment of montelukast is superior to that of short-course.
Objective To analyze the characteristics of intestinal flora in patients with allergic asthma, so as to provide a theoretical basis for the development of new clinical treatment methods. Methods Fecal samples were collected from 14 patients with allergic asthma and 15 healthy people between January 2021 and December 2021, and 16S rRNA was used to analyze the composition and diversity of intestinal flora of the participants. Results There was no statistically significant difference in age, gender, BMI, or smoking history between the allergic asthma group and the control group (all P>0.05). Alpha diversity results showed that there was significant difference in the abundance of intestinal flora between the two groups, but there was no significant difference in the diversity of intestinal flora between the two groups. The results of β diversity analysis indicated that there were significant differences in the composition of bacterial flora between the allergic asthma group and the control group. The difference bacteria between the two groups at the genus level are Faecalibacterium, Roseburia, Alistipes, Sphingomonas, Dorea, Ruminococcaceae_UCG-002, Streptomyces, [Eubacterium]_venturiosum_group, Butyriococcus and Agathobacter. Conclusion Compared with healthy individuals, patients with allergic asthma have undergone significant changes in the composition of their gut microbiota, with various differential bacteria present. Among them, Roseburia and Eubacterium may be involved in the pathogenesis of allergic asthma through changes in short chain fatty acids.
Objective To measure the serum level of adiponectin and explore its clinical implication in patients with asthma in acute exacerbation and remission phase. Methods 97 patients with asthma were recruited, including 50 patients with asthma in acute exacerbation and 47 patients in remission phase fromOctober 2010 to September 2011. 27 healthy nonsmoking volunteers of normal weight ( BMI range of 18.5-24. 9 kg/m2 ) were included as control. The concentrations of adiponectin and tumor necrosis factor alpha ( TNF-α) in serum were measured by enzyme-linked immunosorbent assay ( ELISA) . The lung function was tested in all subjects. The correlations between adiponectin, TNF-αand lung function were investigated. The data was analyzed using SPSS 19. 0 software. Variables were compared with one-way ANOVA. The correlations between variables were analyzed using Peason’s correlation coefficient or Spearman correlation coefficient.Results Serum adiponectin level was significantly lower in the patients with asthma in acute exacerbation [ ( 246 ±1. 21) ng/mL] than that in the healthy subjects [ ( 9. 64 ±4. 88)ng/mL] and the patients in remission phase [ ( 3. 79 ±0. 96) ng/mL] ( P lt; 0. 01) , while serum adiponectin level was also significantly lower in the patients in asthma remission phase than that in the healthy subjects ( P lt; 0. 01) . The serum adiponectin level in the patients with asthma in acute exacerbation or in asthma remission phase was negatively correlated with the serum TNF-α level ( P lt; 0. 01) , and was positively correlated with FEV1 /predicted value ( P lt; 0. 01) . Conclusions The serum adiponectin is reduced in asthma patients and may play a protective role in asthma.
Objective To investigate the effect of myeloid derived suppressor cells ( MDSCs) on airway inflammation of asthmatic mice. Methods Five male BALB/ c mice aged 6 weeks were used for preparing 4T1 tumor bearing mice. Thirty female BALB/ c mice aged six weeks were randomly divided into a normal control group, an athmatic model group, and a cell transplantation group. The MDSCs were separated frommyeloid tissue of tumor-bearing mice using amagnetic cell sorting systemand cultured in RPMI medium 1640 containing GM-CSF. The morphologic characteristics of these cells were observed under lightmicroscope and the phenotypic figures were analyzed with flow cytometry. The mice in the model group and the cell transplantation group were sensitized by ovalbumin and then stimulated with nebulized ovalbumin. The mice in the cell transplantation group were intravenously administered MDSCs which purified by magnetic cell sorting system at 10 days after sensitization. The airway inflammation was evaluated by HE staining. The total and differential cell counts in bronchoalveolar lavage fluid ( BALF) were measured.Results The neutrophil and eosinophil infiltration in pulmonary tissue was dramatically increased in the model group, but not observed in the normal control group and was much milder in the cell transplantation group. The total cell count, the eosinophil and lymphocyte counts in BALF of the model group and the cell transplantation group were significantly higher than those of the normal control group( P lt; 0. 05) , and the number of eosinophils in BALF of the cell transplantation group was decreased when compared with that of the model group( P lt;0. 05) . Conclusion MDSCs via intravenous infusion can effectively suppress airway inflammation in a mouse asthma model.
Objective To investigate the effects of down-regulating of Rfng gene ( 1, 3-Nacetylglucosaminyltransferases) in lung CD4 + T cells of asthmatic rat model by small interfering RNA ( siRNA) and explore the role of Rfng in pathogenesis of asthma. Methods An asthmatic rat model was established by OVA sensitization and challenge. Total T cells were isolated from lung tissue of asthmatic rats, and CD4 + T lymphocytes were purified using magnetic beads. CD4 + T lymphocytes were transfected by siRNA targeting Rfng gene. The mRNA and protein expressions of Rfng were detected by quantitative PCR and Western blot. Quantitative PCR was performed to determine the mRNA levels of Th1 /Th2 cytokines and related genes including IL-12, IFN-γ, IL-4, IL-5, T-bet, and GATA3. ELISA was performed to determine the concentrations of IL-12, IFN-γ, IL-4, and IL-5 in supernatant. Results The mRNA and protein expression of Rfng in RNAi group decreased significantly. IL-12, IFN-γ, T-bet increased and while IL-4, IL-5, and GATA3 decreased significantly. The concentrations of IL-12 and IFN-γ in the supernatant increased significantly, while IL-4 and IL-5 decreased significantly. Conclusions Down regulation of Rfng affects T cell differentiation. It is presumed that Fringe contribute to the pathogenesis of asthma.
ObjectiveTo investigate the effects of resveratrol on airway remodeling in mice with chronic asthma. MethodsTwenty-four female BALB/c mice were randomly divided into three groups (8 mice in each group), namely a control group, an asthma group and a resveratrol (RV) group. All mice were sensitized with ovalbumin (OVA). The sensitized mice were then challenged with OVA while the control group were challenged with phosphate-buffered saline. The mice in the RV group were intraperitoneally injected with RV 30 min before OVA challenge, while the mice in the control and the asthma group were intraperitoneally injected with equal volume of dimethylsulfoxide. Periodic acid-Schiff (PAS) staining was performed to evaluate goblet cell hyperplasia, and Masson-trichrome staining was used to evaluate the deposition of collagen matrix. In addition, immunohistochemical analysis of the α-smooth muscle actin (α-SMA) was applied to examine airway smooth muscle cell hyperplasia and hypertrophy. The positive staining with PAS, Masson, α-SMA areas (μm 2/μm) of per bronchial basement membrane perimeter was used to indicate the degree of airway remodeling. ResultsIn the asthma group and the RV group, the degree of the goblet cell hyperplasia was significantly higher than that in the control group (5.44±1.13, 4.18±0.85vs. 0.00±0.00,P<0.01), and the level of goblet cell hyperplasia in the RV group was lower than that in the asthma group (P<0.05). The Masson staining showed that the deposition of collagen in the asthma group and the RV group was significantly higher than that in the control group (9.80±2.78, 5.71±0.68vs. 1.67±0.65,P<0.01), and the collagen deposition in the RV group was further lower than that in the asthma group (P<0.01). The α-SMA immunohistochemical analysis demonstrated that the expression of α-SMA in the asthma group and the RV group was significantly higher than that in the control group (10.39±1.65, 7.57±1.98vs. 2.41±1.06,P<0.01), and the level of α-SMA in the RV group was also lower than that in the asthma group (P<0.05). ConclusionThese findings suggest that resveratrol has an inhibitory effect on the process of airway remodeling in mice with chronic asthma.
Objective To investigate the expression of the histone deacetylases 1( HDAC1) and the level of whole histone acetylation and methylation in lung T cells of asthmatic rats, and investigate their role in the pathogenesis of asthma.Methods Sixteen wistar rats were randomly divided into a control group and an asthma group( n =8 in each group) . The rats was sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The asthmatic ratmodel was confirmed by measurement of pulmonary function, histochemical staining, HE staining, and the levels of interleukin-4 ( IL-4 ) , interferon-gamma ( IFN-γ) and immunoglobulin E( IgE) in serum and bronchoalveolar lavage fluid ( BALF) . T cells were isolated fromrat lungs and the purity was identified. The expression of the HDAC1, the level of whole histone H3 and H4 acetylation, and whole H3K9 dimethylation were analyzed by Western blot in lung T cells. Results Compared with the control group, the protein expression of HDAC1 was significantly lower( 0. 465±0. 087 vs 0. 790 ±0. 076, P lt;0. 05) in lung T cells of the asthma group. No significant differences werefound in regard to the level of whole histone H3 and H4 acetylation and whole H3K9 dimethylation betweenthe two groups. Conclusions HDAC1 in lung T cells may be involved in the pathogenesis of asthma.Histone modification by HDAC1 may be a specific eventwith gene transcription which may not be associated with asthma.
Objective To explore the characteristics of exercise ventilation function in patients with chronic duration of asthma, and the correlation of cardiopulmonary exercise test and control level and conventional lung function in patients with chronic duration of asthma. Methods Seventy-three patients with chronic duration of asthma admitted from December 2021 to December 2022 were recruited in the study. The asthma control level was assessed with the asthma control test (ACT) and the patients were divided into a well-controlled group and a poorly-controlled group. Routine pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) were performed in both groups, to analyze the difference of related parameters between the two groups and observe the correlation between CPET and PFT, ACT score in the patients with chronic persistent asthma. Results CPET results showed that the VE/VCO2 slope, anaerobic threshold carbon dioxide equivalent (EqCO2@AT), and physiologically ineffective peak during exercise (VD/VTpeak) were higher in the poorly-controlled group than those in the well-controlled group (all P<0.05). The peak minute ventilation (VEpeak) and tidal volume (VTpeak) of the patients in the poorly-controlled group were lower than those in the well-controlled group (both P<0.05). The peak respiratory rate (BFpeak) and respiratory reserve (BRpeak) of the two groups were not significantly different (both P>0.05). The results of correlation analysis showed that the VE/VCO2 slope, EqCO2@AT, VD/VTpeak were negatively correlated with ACT score, and VEpeak was positively correlated with FVC%pred and MMEF%pred in the patients with chronic persistent asthma. BRpeak was positively correlated with FEV1%pred, FEV1/FVC%pred, MMEF%pred in routine pulmonary function. Multivariate logistic regression analysis showed that the increase of VE/VCO2 slope and VD/VTpeak were independent risk factors for poor asthma control (P<0.05). Conclusions Patients with poorly-controlled asthma have decreased exercise ventilatory function, mainly showing decreased ventilation and tidal volume during peak exercise and decreased ventilatory efficiency. There is some correlation between exercise ventilatory function and conventional lung function of control level in patients with chronic duration of asthma. The relevant indicators of ventilation efficiency in CPET have suggestive significance for asthma that is not well controlled, so it is necessary to carry out CPET in patients with asthma to improve the comprehensive evaluation of asthma.