Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product v...Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.展开更多
THE incidence of gastroesophageal reflux disease （GERD） is high in Western nations. Its extraesophageal manifestations such as asthma, paroxysmal laryngospasm, and excessive throat phlegm,
ESPITE the strong association between gastroesophageal reflux disease （GERD） and asthma has been undisputedly established and widely recognized by experts in advanced countries. Yet few topics in medicine are as con...ESPITE the strong association between gastroesophageal reflux disease （GERD） and asthma has been undisputedly established and widely recognized by experts in advanced countries. Yet few topics in medicine are as controversial as the causal relationship between GERD and asthma： some argue that GERD causes asthma, while others think the other way around is true, still quite a few believe that bronchodilator medications are to blame. This controversy continues to be a conundrum or more piece of the puzzle.1 We would like to share two thoughts which might be a belated revelation with scholars and experts and invite them for further cooperative studies： the GERD-derived respiratory distress is not asthma, but GERD pure and simple; and the pathogenesis of respiratory distress is not asthma, but laryngotracheal irritation/spasm/suffocation.展开更多
Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory...Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.展开更多
To measure Derp1 and Blot5 allergen levels in asthmatics’ homes in Hongkong. Methods Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients’ hous...To measure Derp1 and Blot5 allergen levels in asthmatics’ homes in Hongkong. Methods Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients’ house: bed and floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique. Results The levels of Derp1 allergens found in bed (geometric mean (GM) 3.43 μg/g of dust; 95%CI, 1.89-4.96 μg/g) and on the floor (GM 1.12 μg/g of dust; 95%CI, 0.71-1.53 μg/g) indicated significant differences (P = 0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 μg/g of dust; 95%CI, 0.89-38.90 μg/g) and on the floor (GM 6.14 μg/g of dust; 95%CI, 0.40-11.90 μg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derp1 and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 ≥ 10 μg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P < 0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0 μg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5% respectively, P < 0.05). Conclusions Derp1 and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus(Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hong-kong.展开更多
Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation as...Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.展开更多
Wheezing disease( bronchial asthma) is a common but refractory disease among pulmonary diseases. It tends to attack repeatedly,and is difficult to be cured. In recent years,some studies have shown that effective tradi...Wheezing disease( bronchial asthma) is a common but refractory disease among pulmonary diseases. It tends to attack repeatedly,and is difficult to be cured. In recent years,some studies have shown that effective traditional Chinese medicine( TCM) nursing interventions on the wheezing disease can significantly ameliorate the treatment compliance of patients,reduce the attack and improve the quality of life. Therefore,it is important for patients with different patterns of syndrome to receive effective and reasonable TCMnursing intervention. This article mainly explored the key points of common syndromes,TCMnursing methods and health guidance of wheezing disease in order to further develop the advantages of TCM,improve its efficacy and standardized its nursing behavior.展开更多
BACKGROUND： Few studies have reported the effects of early tracheotomy in acute severe asthmatic patients. We report two patients with acute severe asthma who were successfully treated with early tracheotomy. METHOD...BACKGROUND： Few studies have reported the effects of early tracheotomy in acute severe asthmatic patients. We report two patients with acute severe asthma who were successfully treated with early tracheotomy. METHODS：The two patients with acute severe asthma were retrospectively reviewed. They had been treated at the Department of Emergency and Critical Care, Renji Hospital, Shanghai Jiaotong University School of Medicine. RESULTS： They developed progressively hypercapnia and severe acidosis, and were not improved after conventional therapies. Early tracheotomy after mechanical ventilation decreased airway resistance and work of breathing, and corrected hypercapnia and acidosis. Adequate gas exchange was maintained after tracheotomy. The two patients were subsequently weaned from mechanical ventilation and discharged. CONCLUSION：Early tracheotomy could be a valuable approach in certain patients with severe asthma.展开更多
Objective.In this study,we investigated the hypothesis that tumor necrosis factor(TNF)α-308gene polymorphism might be of the genetic predisposition to asthma and asthma phenotypes.Methods.TNFα-308gene polymorphism w...Objective.In this study,we investigated the hypothesis that tumor necrosis factor(TNF)α-308gene polymorphism might be of the genetic predisposition to asthma and asthma phenotypes.Methods.TNFα-308gene polymorphism was genotyped in221random unrelated Northern Chinese population(comprising125asthmatics and96healthy controls)and52individuals from12asthmatic families with Han ethnic by using polymerase chain reaction(PCR)-restriction fragment length polymor-phism(RFLP).Methacholine(Mch)broncho-challenge test,bronchial reversibility test and lung function were underwent in all asthmatics.Results.TNFα-3082homozygosity was present at a significantly higher frequency in asthmatics than that in controls(20.8%vs11.4%,P<0.05,OR2.259),the TNF allele2was also higher in asthmatics compared with controls(0.42vs0.33,P<0.01).TNFα-3082homozygosity was an weak independent risk factor for asthma etiology(OR0.226,P<0.05).Moreover,patients carrying TNFα-3082homozy-gosity had less responsive to inhaledβ 2 -agonist in20minutes than patients carrying other two genotypes(24.1%vs29.5%vs38.8%,P<0.05).Linkage analysis didn’t support that TNFαgene was linked to asthma (Likelihood of odds,LOD<1)based on familial data.Conclusion These results suggest that TNFα-3082homozygosity may be of a component contribut-ing to the genetic predisposition to asthma ,and airway responsiveness toβ2 -agonist.展开更多
Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered...Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered before OVA sensitization group, BCG DNA administered after OVA challenge group. The asthma models were developed by immunizing BALB/C mice with OVA. A total of 100 μg BCG DNA was intratracheally administered before OVA sensitization and after OVA challenge. WBC count and eosinophil percentage (EOS%) in bronchoalveolar lavage fluid (BALF) were measured. Changes of IL 4 , IL 5,IL 12, IFN γ in BALF were determined by ELISA. Pulmonary inflammation was observed on normal pathological slides and the proliferation and mucus secretion of goblet cells stained by AB PAS were also observed. Results: IL 4 , IL 5,IL 12, IFN γ in BALF of normal control group were(32.3±5.7)pg/ml,(15.6±3.9)pg/ml,(80±8.5)pg/ml,(153.2±9.4)pg/ml respectively. IL 4,IL 5 in BALF of asthma model group increased to (299±15.6)pg/ml and (206.7±9.3)pg/ml, while IL 12 and IFN γ decreased to (20.4±4.1)pg/ml and (51.6±5.5) pg/ml respectively. BCG DNA administered intratracheally before OVA sensitization and after OVA challenge significantly increased IL 12 [(71.6±8.3)pg/ml,(67.8±8.1pg/ml)] and IFN γ [(119.0±11.3)pg/ml,(114.7±10.1)pg/ml] in the BALF. Meanwhile, BCG DNA decreased IL 4 [(82.1±6.1)pg/ml,(86.3±5.9)pg/ml] and IL 5 [(32.3±4.6)pg/ml,(37.4±5.3)pg/ml]. Eosinophil level in BALF was inhibited and the pulmonary inflammation was dramatically relieved compared to asthma model group. Conclusion: Intratracheally administered BCG DNA can induce IL 12 and IFN γ secretion,inhibit Th2 response which can relieve allergic airway inflammation and provide a new way in the treatment and prevention of asthma.展开更多
BACKGROUND： Lidocaine can promote the apoptosis of eosinophils, which is normallydelayed by IL-5; it has a good effect on serious steroid resistant asthma （SRA）. The study aimed toexplore the effect of nebulized li...BACKGROUND： Lidocaine can promote the apoptosis of eosinophils, which is normallydelayed by IL-5; it has a good effect on serious steroid resistant asthma （SRA）. The study aimed toexplore the effect of nebulized lidocaine inhalation on asthma.METHODS： It was a randomized, double-blind, placebo-controlled and prospective study. A totalof 36 patients with acute asthma were divided into groups A1, A2, B1 and B2, with 9 patients in eachgroup. The patients of groups A1 and A2 had steroid resistant asthma （SRA） and those of groups B1and B2 had steroid sensitive asthma （SSA）. Patients in groups A2 and B1 were administered nebulizedlidocaine in addition to routine treatment, while patients in groups A1 and B2 were given nebulizednormal saline apart from routine treatment and served as placebo-controlled groups.RESULTS： There were signifi cant differences in heart rate, respiratory rate, and peak fi ow rate andforced expiratory volume in one second between the experimental groups and the placebo-controlledgroups. There was no signifi cant difference between groups A2 and B1, and between A1 and B2.CONCLUSION： Inhaled lidocaine is benefi cial to asthma patients, especially those with steroid-resistant asthma.展开更多
Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin(OVA),and explore the possible mechanism.Methods Culture the B.pertussis in Bordet-Gengou agar containing 25% rabb...Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin(OVA),and explore the possible mechanism.Methods Culture the B.pertussis in Bordet-Gengou agar containing 25% rabbit blood.Collect the bacteria and inactive them at 80 ℃ for 30 min to get whole killed B.pertussis.32 BALB/C mice were randomly divided into control group,model-control group,model group and treatment group.The mice were sensitized and challenged with OVA to establish asthma model.Asthma mice in treatment group were orally administrated with B.pertussis 7 days before sensitization.The mice in control group and model-control group were challenged with saline.After 24 hours of last challenge,bronchoaveolar lavage fluid(BALF)and peripheral blood were collected.The total cells and eosinophils were counted in BALF.Results Compared with the control group(2.03±0.42,0.33±0.82)×105 mL-1 and model-control group(2.16±0.48,0.16±0.41)×105 mL-1,the total cells(10.13±1.33)×105 mL-1 and eosinophils(11.83±4.573)×105 mL-1 in BALF were more in asthma mice(P<0.01).The number of total cells(5.50±1.55)×105 mL-1 and eosinophils(0.66±0.82)×105 mL-1 in BALF were reduced in asthma mice treated with B.pertussis compared with asthma mice(P<0.01).Conclusions Oral B.pertussis can inhabit airway inflammation of asthma mice and has the potential of treating asthma.展开更多
Objective To investigate the effect of Xiaofenghuoxue decotion(XFHX)on the production of Th1 and Th2 cytokine in bronchoalveolar lavage fluid(BALF)in asthma guinea pigs sensitized and challenged with ovalbumin.Methods...Objective To investigate the effect of Xiaofenghuoxue decotion(XFHX)on the production of Th1 and Th2 cytokine in bronchoalveolar lavage fluid(BALF)in asthma guinea pigs sensitized and challenged with ovalbumin.Methods The animals were randomly divided into 5 groups:the normal control group,the asthma group,the XFHX high dose group,the XFHX low dose group and the budesonide group.2 weeks after sensitization with a mixture of 10% OVA and 10% Al(OH)3,the drugs were given to the animals for 7 days,and then the animals were challenged with aerosol of 1% ovalbumin,the latency time for the onset of respiratory abnormalities was examined,BALF was collected 16 h after.Leukocyte in BALF was counted.The level of IFN-γ reduced by Th1 cells and IL-4 and IL-5 produced by Th2 cells were determined by EILSA.NO contents were also examined.Results The latency time for the onset of respiratory abnormalities and leukocyte infiltration in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The level of IFN-γ in both XFHX high dose group and low dose group significantly increased compared with the asthma group,the level of IL-4 and IL-5 in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The production of NO was inhibited in both XFHX high dose group and low dose group compared with the asthma group.Conclusions These results suggest that the anti-asthma effect of Xiaofenghuoxue decotion is associated with NO regulated reversal of Th1/Th2 cytokine balance in allergen-induced asthma guinea pigs.展开更多
Background:As asthma symptoms worsen,patients typically rely on short-actingβ2-agonist(SABA)rescue therapy,but SABAs do not address worsening inflammation,which leaves patients at risk for severe asthma exacerbations...Background:As asthma symptoms worsen,patients typically rely on short-actingβ2-agonist(SABA)rescue therapy,but SABAs do not address worsening inflammation,which leaves patients at risk for severe asthma exacerbations.The use of a fixed-dose combination of albuterol and budesonide,as compared with albuterol alone,as rescue medication might reduce the risk of severe asthma exacerbation.展开更多
Guinea pig model of asthma was established with the sensitization of the animals with aerosolized ovalbumin. A group of asthmatic guinea pigs were treated with tripholide. It was found that the airway responsiveness t...Guinea pig model of asthma was established with the sensitization of the animals with aerosolized ovalbumin. A group of asthmatic guinea pigs were treated with tripholide. It was found that the airway responsiveness to histamine was markedly higher in the asthmatic group than in the control. The total cell count, absolute eosinophil count, percentage of hypodense eosinophils and the level of eosinophil viability enhancing activity in the bronchoalveolar lavage fluid (BALF) were significantly higher in the asthmatic group than in the control. The percentage of hypodense eosinophils and absolute eosinophil count were in close correlation with airway responsiveness (r= -0. 76 and - 0. 88, P <0. 05 and 0. 01 respectively). Treatment of the asthmatic guinea pigs with tripholide (8 μg/kg, given orally for 7 d) significantly reduced the airway responsiveness and decreased the percentage of hypodense eosinophils and the level of eosinophil viability enhancing activity but eosinophilia in BALF was not affected. It was concluded that tripholide exerts its effects to decrease airway responsiveness in asthma through its action to reduce active hypodense eosinophils.展开更多
The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of...The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of GR was 12908+2501 sites cell which wa展开更多
To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern ...To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 un-related asthmatic individuals and 96 healthy controls. β2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial rever-sibility by β2-agonist evaluated. Results (1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 ± 0.3, 1.6 ± 0.8, and 2.1 ± 3.0 μmol/L,P < 0.05). Conclusion β2-AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. β2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.展开更多
Objective The aim of the study was to determine whether bronchial asthma was associated with increased levels of soluble intercellular adhesion molecule 1(sICAM 1) in serum, which might be ...Objective The aim of the study was to determine whether bronchial asthma was associated with increased levels of soluble intercellular adhesion molecule 1(sICAM 1) in serum, which might be valuble data for the effective therapy of these patients Patients and methods The concentrations of sICAM 1 were determined in sera of healthy donors and asthmatic patients using a sensitive enzyme immunoassay Results The mean(±SD) levels of serum sICAM 1 of 26 asthmatic patients (205±72 0 μg/L)was significantly higher than that of the 30 healthy volunteers (154±63 9 μg/L,P<0 01) There was no much difference between the serum levels in 12 patients suffering from atopic asthma and the levels in 14 patients with nonatopic asthma The serum concentrations of sICAM 1 were higher during asthma attacks than that during remissions in the same patients (P<0 05) Conclusion These results suggest that sICAM 1 may play a certain role in the pathophysiology of bronchial asthma,and might be signals for successful treatment展开更多
Objective:To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the ...Objective:To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the possible mode of inheritance. Methods: A genetic model-free approach was used to perform a meta analysis. Heterogeneity, sensitivity analysis and publication bias were also explored. Results: Our meta analysis summarized the evidence to date regarding the association of C-589T and C-590T polymorphisms in the promoter region of IL-4 gene with asthma. For C-590T, the results showed a significant recessive genetic model, and the CC genotype was about 24% less likely to have asthma than the genotype CT and TT. Although there was evidence suggesting a recessive genetic model for C-589T, the recessive model was not statistically significant. Conclusion: This meta analysis suggests that there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of asthma.展开更多
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2021B15151300042021B1515140021)+2 种基金the Scientific Research Start-up Funding of Guangdong Medical University(1026/4SG21229G)China Postdoctoral Science Foundation(2021M702781)Guangdong Medical University Post-doctoral Research Funding(2BH19006P)。
文摘Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.
文摘THE incidence of gastroesophageal reflux disease （GERD） is high in Western nations. Its extraesophageal manifestations such as asthma, paroxysmal laryngospasm, and excessive throat phlegm,
文摘ESPITE the strong association between gastroesophageal reflux disease （GERD） and asthma has been undisputedly established and widely recognized by experts in advanced countries. Yet few topics in medicine are as controversial as the causal relationship between GERD and asthma： some argue that GERD causes asthma, while others think the other way around is true, still quite a few believe that bronchodilator medications are to blame. This controversy continues to be a conundrum or more piece of the puzzle.1 We would like to share two thoughts which might be a belated revelation with scholars and experts and invite them for further cooperative studies： the GERD-derived respiratory distress is not asthma, but GERD pure and simple; and the pathogenesis of respiratory distress is not asthma, but laryngotracheal irritation/spasm/suffocation.
基金supported by grants awarded to YY by the National Natural Science Foundation of China (81870019, 82170029)the Guangdong Provincial Natural Science Foundation (2018A030313554)+3 种基金the Innovation Research Team for Basic and Clinical Studies on Chronic Liver Diseases of 2018 High-Level Health Teams of ZhuhaiYKQ by the National Natural Science Foundation of China (82002612)the Chinese Postdoctoral Science Foundation (2019M660211)ZGC by the Science and Technology Program of Guangzhou,China (201704020179)。
文摘Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.
文摘To measure Derp1 and Blot5 allergen levels in asthmatics’ homes in Hongkong. Methods Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients’ house: bed and floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique. Results The levels of Derp1 allergens found in bed (geometric mean (GM) 3.43 μg/g of dust; 95%CI, 1.89-4.96 μg/g) and on the floor (GM 1.12 μg/g of dust; 95%CI, 0.71-1.53 μg/g) indicated significant differences (P = 0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 μg/g of dust; 95%CI, 0.89-38.90 μg/g) and on the floor (GM 6.14 μg/g of dust; 95%CI, 0.40-11.90 μg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derp1 and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 ≥ 10 μg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P < 0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0 μg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5% respectively, P < 0.05). Conclusions Derp1 and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus(Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hong-kong.
基金This project was supported by the National Sciences andTechnology Commission of China(No.96-906-02-04)and GlaxoWellcome Ltd
文摘Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.
文摘Wheezing disease( bronchial asthma) is a common but refractory disease among pulmonary diseases. It tends to attack repeatedly,and is difficult to be cured. In recent years,some studies have shown that effective traditional Chinese medicine( TCM) nursing interventions on the wheezing disease can significantly ameliorate the treatment compliance of patients,reduce the attack and improve the quality of life. Therefore,it is important for patients with different patterns of syndrome to receive effective and reasonable TCMnursing intervention. This article mainly explored the key points of common syndromes,TCMnursing methods and health guidance of wheezing disease in order to further develop the advantages of TCM,improve its efficacy and standardized its nursing behavior.
文摘BACKGROUND： Few studies have reported the effects of early tracheotomy in acute severe asthmatic patients. We report two patients with acute severe asthma who were successfully treated with early tracheotomy. METHODS：The two patients with acute severe asthma were retrospectively reviewed. They had been treated at the Department of Emergency and Critical Care, Renji Hospital, Shanghai Jiaotong University School of Medicine. RESULTS： They developed progressively hypercapnia and severe acidosis, and were not improved after conventional therapies. Early tracheotomy after mechanical ventilation decreased airway resistance and work of breathing, and corrected hypercapnia and acidosis. Adequate gas exchange was maintained after tracheotomy. The two patients were subsequently weaned from mechanical ventilation and discharged. CONCLUSION：Early tracheotomy could be a valuable approach in certain patients with severe asthma.
文摘Objective.In this study,we investigated the hypothesis that tumor necrosis factor(TNF)α-308gene polymorphism might be of the genetic predisposition to asthma and asthma phenotypes.Methods.TNFα-308gene polymorphism was genotyped in221random unrelated Northern Chinese population(comprising125asthmatics and96healthy controls)and52individuals from12asthmatic families with Han ethnic by using polymerase chain reaction(PCR)-restriction fragment length polymor-phism(RFLP).Methacholine(Mch)broncho-challenge test,bronchial reversibility test and lung function were underwent in all asthmatics.Results.TNFα-3082homozygosity was present at a significantly higher frequency in asthmatics than that in controls(20.8%vs11.4%,P<0.05,OR2.259),the TNF allele2was also higher in asthmatics compared with controls(0.42vs0.33,P<0.01).TNFα-3082homozygosity was an weak independent risk factor for asthma etiology(OR0.226,P<0.05).Moreover,patients carrying TNFα-3082homozy-gosity had less responsive to inhaledβ 2 -agonist in20minutes than patients carrying other two genotypes(24.1%vs29.5%vs38.8%,P<0.05).Linkage analysis didn’t support that TNFαgene was linked to asthma (Likelihood of odds,LOD<1)based on familial data.Conclusion These results suggest that TNFα-3082homozygosity may be of a component contribut-ing to the genetic predisposition to asthma ,and airway responsiveness toβ2 -agonist.
文摘Objective: To investigate the effect of intratracheally administered BCG DNA on a murine model of asthma. Methods: BALB/C mice were divided into 4 groups: normal control group, asthma model group, BCG DNA administered before OVA sensitization group, BCG DNA administered after OVA challenge group. The asthma models were developed by immunizing BALB/C mice with OVA. A total of 100 μg BCG DNA was intratracheally administered before OVA sensitization and after OVA challenge. WBC count and eosinophil percentage (EOS%) in bronchoalveolar lavage fluid (BALF) were measured. Changes of IL 4 , IL 5,IL 12, IFN γ in BALF were determined by ELISA. Pulmonary inflammation was observed on normal pathological slides and the proliferation and mucus secretion of goblet cells stained by AB PAS were also observed. Results: IL 4 , IL 5,IL 12, IFN γ in BALF of normal control group were(32.3±5.7)pg/ml,(15.6±3.9)pg/ml,(80±8.5)pg/ml,(153.2±9.4)pg/ml respectively. IL 4,IL 5 in BALF of asthma model group increased to (299±15.6)pg/ml and (206.7±9.3)pg/ml, while IL 12 and IFN γ decreased to (20.4±4.1)pg/ml and (51.6±5.5) pg/ml respectively. BCG DNA administered intratracheally before OVA sensitization and after OVA challenge significantly increased IL 12 [(71.6±8.3)pg/ml,(67.8±8.1pg/ml)] and IFN γ [(119.0±11.3)pg/ml,(114.7±10.1)pg/ml] in the BALF. Meanwhile, BCG DNA decreased IL 4 [(82.1±6.1)pg/ml,(86.3±5.9)pg/ml] and IL 5 [(32.3±4.6)pg/ml,(37.4±5.3)pg/ml]. Eosinophil level in BALF was inhibited and the pulmonary inflammation was dramatically relieved compared to asthma model group. Conclusion: Intratracheally administered BCG DNA can induce IL 12 and IFN γ secretion,inhibit Th2 response which can relieve allergic airway inflammation and provide a new way in the treatment and prevention of asthma.
文摘BACKGROUND： Lidocaine can promote the apoptosis of eosinophils, which is normallydelayed by IL-5; it has a good effect on serious steroid resistant asthma （SRA）. The study aimed toexplore the effect of nebulized lidocaine inhalation on asthma.METHODS： It was a randomized, double-blind, placebo-controlled and prospective study. A totalof 36 patients with acute asthma were divided into groups A1, A2, B1 and B2, with 9 patients in eachgroup. The patients of groups A1 and A2 had steroid resistant asthma （SRA） and those of groups B1and B2 had steroid sensitive asthma （SSA）. Patients in groups A2 and B1 were administered nebulizedlidocaine in addition to routine treatment, while patients in groups A1 and B2 were given nebulizednormal saline apart from routine treatment and served as placebo-controlled groups.RESULTS： There were signifi cant differences in heart rate, respiratory rate, and peak fi ow rate andforced expiratory volume in one second between the experimental groups and the placebo-controlledgroups. There was no signifi cant difference between groups A2 and B1, and between A1 and B2.CONCLUSION： Inhaled lidocaine is benefi cial to asthma patients, especially those with steroid-resistant asthma.
文摘Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin(OVA),and explore the possible mechanism.Methods Culture the B.pertussis in Bordet-Gengou agar containing 25% rabbit blood.Collect the bacteria and inactive them at 80 ℃ for 30 min to get whole killed B.pertussis.32 BALB/C mice were randomly divided into control group,model-control group,model group and treatment group.The mice were sensitized and challenged with OVA to establish asthma model.Asthma mice in treatment group were orally administrated with B.pertussis 7 days before sensitization.The mice in control group and model-control group were challenged with saline.After 24 hours of last challenge,bronchoaveolar lavage fluid(BALF)and peripheral blood were collected.The total cells and eosinophils were counted in BALF.Results Compared with the control group(2.03±0.42,0.33±0.82)×105 mL-1 and model-control group(2.16±0.48,0.16±0.41)×105 mL-1,the total cells(10.13±1.33)×105 mL-1 and eosinophils(11.83±4.573)×105 mL-1 in BALF were more in asthma mice(P<0.01).The number of total cells(5.50±1.55)×105 mL-1 and eosinophils(0.66±0.82)×105 mL-1 in BALF were reduced in asthma mice treated with B.pertussis compared with asthma mice(P<0.01).Conclusions Oral B.pertussis can inhabit airway inflammation of asthma mice and has the potential of treating asthma.
文摘Objective To investigate the effect of Xiaofenghuoxue decotion(XFHX)on the production of Th1 and Th2 cytokine in bronchoalveolar lavage fluid(BALF)in asthma guinea pigs sensitized and challenged with ovalbumin.Methods The animals were randomly divided into 5 groups:the normal control group,the asthma group,the XFHX high dose group,the XFHX low dose group and the budesonide group.2 weeks after sensitization with a mixture of 10% OVA and 10% Al(OH)3,the drugs were given to the animals for 7 days,and then the animals were challenged with aerosol of 1% ovalbumin,the latency time for the onset of respiratory abnormalities was examined,BALF was collected 16 h after.Leukocyte in BALF was counted.The level of IFN-γ reduced by Th1 cells and IL-4 and IL-5 produced by Th2 cells were determined by EILSA.NO contents were also examined.Results The latency time for the onset of respiratory abnormalities and leukocyte infiltration in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The level of IFN-γ in both XFHX high dose group and low dose group significantly increased compared with the asthma group,the level of IL-4 and IL-5 in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The production of NO was inhibited in both XFHX high dose group and low dose group compared with the asthma group.Conclusions These results suggest that the anti-asthma effect of Xiaofenghuoxue decotion is associated with NO regulated reversal of Th1/Th2 cytokine balance in allergen-induced asthma guinea pigs.
文摘Background:As asthma symptoms worsen,patients typically rely on short-actingβ2-agonist(SABA)rescue therapy,but SABAs do not address worsening inflammation,which leaves patients at risk for severe asthma exacerbations.The use of a fixed-dose combination of albuterol and budesonide,as compared with albuterol alone,as rescue medication might reduce the risk of severe asthma exacerbation.
文摘Guinea pig model of asthma was established with the sensitization of the animals with aerosolized ovalbumin. A group of asthmatic guinea pigs were treated with tripholide. It was found that the airway responsiveness to histamine was markedly higher in the asthmatic group than in the control. The total cell count, absolute eosinophil count, percentage of hypodense eosinophils and the level of eosinophil viability enhancing activity in the bronchoalveolar lavage fluid (BALF) were significantly higher in the asthmatic group than in the control. The percentage of hypodense eosinophils and absolute eosinophil count were in close correlation with airway responsiveness (r= -0. 76 and - 0. 88, P <0. 05 and 0. 01 respectively). Treatment of the asthmatic guinea pigs with tripholide (8 μg/kg, given orally for 7 d) significantly reduced the airway responsiveness and decreased the percentage of hypodense eosinophils and the level of eosinophil viability enhancing activity but eosinophilia in BALF was not affected. It was concluded that tripholide exerts its effects to decrease airway responsiveness in asthma through its action to reduce active hypodense eosinophils.
文摘The maximal binding capacity(R0) and dissociation constant(Kd) of glucocorticoid receptors(GR) in peripheral leucocytes and the cortisol(F) level in plasma were estimated in 17 patients with bronchial asthma.The R0 of GR was 12908+2501 sites cell which wa
文摘To investigate whether the polymorphisms of β2-adrenergic receptor (β2-AR) at position 16, 27, 164 are asso-ciated with asthma in Northern Chinese subjects. Methods Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 un-related asthmatic individuals and 96 healthy controls. β2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial rever-sibility by β2-agonist evaluated. Results (1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 ± 0.3, 1.6 ± 0.8, and 2.1 ± 3.0 μmol/L,P < 0.05). Conclusion β2-AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. β2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.
文摘Objective The aim of the study was to determine whether bronchial asthma was associated with increased levels of soluble intercellular adhesion molecule 1(sICAM 1) in serum, which might be valuble data for the effective therapy of these patients Patients and methods The concentrations of sICAM 1 were determined in sera of healthy donors and asthmatic patients using a sensitive enzyme immunoassay Results The mean(±SD) levels of serum sICAM 1 of 26 asthmatic patients (205±72 0 μg/L)was significantly higher than that of the 30 healthy volunteers (154±63 9 μg/L,P<0 01) There was no much difference between the serum levels in 12 patients suffering from atopic asthma and the levels in 14 patients with nonatopic asthma The serum concentrations of sICAM 1 were higher during asthma attacks than that during remissions in the same patients (P<0 05) Conclusion These results suggest that sICAM 1 may play a certain role in the pathophysiology of bronchial asthma,and might be signals for successful treatment
基金Supported by a grant from the Science Foundation of Third Military Medical University (No. XG200353)
文摘Objective:To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the possible mode of inheritance. Methods: A genetic model-free approach was used to perform a meta analysis. Heterogeneity, sensitivity analysis and publication bias were also explored. Results: Our meta analysis summarized the evidence to date regarding the association of C-589T and C-590T polymorphisms in the promoter region of IL-4 gene with asthma. For C-590T, the results showed a significant recessive genetic model, and the CC genotype was about 24% less likely to have asthma than the genotype CT and TT. Although there was evidence suggesting a recessive genetic model for C-589T, the recessive model was not statistically significant. Conclusion: This meta analysis suggests that there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of asthma.
