Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic...Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats were less sensitive to DXM treatment.Anti-HMGB1 treatment attenuated airway hyperresponsiveness,inflammation,and remodeling in SRA rats to a certain extent and was accompanied by lower levels of IL-17 （（369.2±126.7） vs.（780.5±261.7） pg/ml in control SRA rats） in BALF （P ＜0.05）.Low-intensity aerobic exercise training decreased the expression of both HMGB1 （（14.1±2.9） vs.（21.2±4.5） ng/ml in control SRA rats） and IL-17 （（545.3±148.6） vs.（780.5±261.7） pg/ml in control SRA rats） in BALF （all P ＜0.05） and was accompanied by improved airway hyperresponsiveness,inflammation,and remodeling in SRA rats （all P ＜0.05）.Conclusions Low-intensity aerobic exercise training attenuated airway hyperresponsiveness,inflammation,and remodeling in a rat model of SPA.Decreased HMGB1 and IL-17 levels in BALF by aerobic exercise training at least partly contributed to the improvements of SPA.展开更多
Steroid resistance represents a major clinical problem in the treatment of severe asthma,and therefore a better understanding of its pathogenesis is warranted.Recent studies indicated that histone deacetylase 2(HDAC2)...Steroid resistance represents a major clinical problem in the treatment of severe asthma,and therefore a better understanding of its pathogenesis is warranted.Recent studies indicated that histone deacetylase 2(HDAC2)and interleukin 17A(IL-17A)play important roles in severe asthma.HDAC2 activity is reduced in patients with severe asthma and smoking-induced asthma,perhaps accounting for the amplified expression of inflammatory genes,which is associated with increased acetylation of glucocorticoid receptors.Neutrophilic inflammation contributes to severe asthma and may be related to T helper(Th)17 rather than Th2 cytokines.IL-17A levels are elevated in severe asthma and correlate with the presence of neutrophils.Restoring the activity of HDAC2 or targeting the Th17 signaling pathway is a potential therapeutic approach to reverse steroid insensitivity.展开更多
AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 ...AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included.By exclusion criteria,8460 subjects were screened with 1676 myopia samples and 6784 control samples.Subsequently,baseline characteristics,association analyses,risk stratification analyses,and receive operating characteristic curve(ROC)were used to investigate the associations between covariates and myopia.Then,the causal relationship was explored in depth by MR analysis,and was estimated the reliability by sensitivity analyses and directionality tests.RESULTS:Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates(excluding gender;P<0.05).The results in all three models indicated that asthma was strongly associated with myopia and the effect on myopia was not significantly confounded by other covariates[model 3:odd ratio(OR)=1.31;95%CI=1.07-1.62;P=0.0133].The risk stratification analysis again verified that asthma remained strongly associated with myopia and was a risk factor for myopia(P<0.05,OR>1).ROC proved that the model was accurate in its prediction[area under curve(AUC)=0.7].Subsequently,the causal relationship between them was statistically significant(P<0.05)according to the inverse variance weighted(IVW)method in MR.Scatterplot showed that asthma and myopia had significant positive causality and were not affected by confounders.Forest plot displayed an increasing risk of myopia on asthma(OR>1).The funnel plot demonstrated compliance with Mendel’s second law.Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.CONCLUSION:A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis,which is important implications for public health policy development and clinical practice.展开更多
Objective: To observe the clinical efficacy and safety of low dose tacrolimus (TAC) combined with tripterygium (TW) in treatment of steroid resistant nephritic syndrome (SRNS). Method: The patients, who were diagnosed...Objective: To observe the clinical efficacy and safety of low dose tacrolimus (TAC) combined with tripterygium (TW) in treatment of steroid resistant nephritic syndrome (SRNS). Method: The patients, who were diagnosed with mesangial proliferative glomerulonephritis (MesPGN) and focal segmental glomerulosclerosis (FSGS) by biopsy and failed to respond to a 3-month treatment with prednisone (1 mg/kg·d), were randomly divided into 2 groups (TAC + TW Group and TW Group). Initially TAC + TW group took TAC 0.05mg/(kg·d) 2 h after meal at 12 h interval. The plasma TAC level was examined after 3 days and was kept at 1.5 - 4 ng·ml;meanwhile, TW was given at 60 mg/d before meal. TW group only took TW (60 mg/d). The efficacy, adverse reactions and plasma TAC levels were observed in each group. Results: 1) Totally 20 SRNS patients completed the trial, 11 of TAC + TW Group and 9 of TW Group. There is no statistical difference between the two groups in terms of age, gender, duration since onset of the disease, blood pressure, 24 h UPQ, serum albumin, creatinine, cholesterol, triglyceride, FBG, kidney pathological categories, time of taking prednisone etc.;2) Urine protein started to decrease after 1 month treatment in both of TAC + TW and TW groups. By the 12th month of treatment, TAC + TW group showed 8 cases of complete remission (72.7%), 2 cases of partial remission (18.2%) and 1 case of no improvement (9.1%), while those of TW groups were 2 (22.2%), 4 (44.5%) and 3 (33.3%), respectively;3) With treatment, the TAC + TW Group patients’ plasma protein was significantly higher than that of pretreatment stage and recovered to normal level after 6 month of treatment. However, there was no significant plasma protein increase in TW Group. No obvious changes were observed on serum creatinine level of patients of both the two groups;4) The incidence of adverse reactions was not significantly different between the two groups. Conclusion: TAC + TW reduced proteinuria of SRNS patients, increased clinical remission rate and was tolerant to SRNS patients. We conclude that TAC + TW treatment is an effective way to treat patients with SRNS.展开更多
Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalitie...Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalities or variants appeared?to be influenced by race and ethnic group. We have investigated?probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children?with primary SRNS?whovisited?the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were?conducted through screenings?for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing.?Fisher’s Exact Test was used to determine?the?correlation?between?NPHS2 polymorphisms and clinical manifestations.Results:?Seven?females (25%) and 21 males (75%)?participated in the study.?The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.?We identified 6 NPHS2polymorphisms,?i.e.?g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation?was found. There was?no correlation?between?NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The?results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.展开更多
BACKGROUND Crumbs homolog 2(CRB2)is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes;mutations can directly lead to steroid-resistant nephrotic syndrome(SRNS).Howev...BACKGROUND Crumbs homolog 2(CRB2)is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes;mutations can directly lead to steroid-resistant nephrotic syndrome(SRNS).However,the characteristics of nephrotic syndrome(NS)caused by CRB2 mutations have not been described.CASE SUMMARY We report a novel compound heterozygous mutation of the CRB2 gene in two siblings with SRNS.The two siblings had edema,proteinuria,hypoproteinemia and hyperlipidemia.Both their father and mother had normal phenotypes(no history of NS).Whole exon sequencing(WES)of the family showed a novel compound heterozygous mutation,c.2290(exon 8)C>T and c.3613(exon 12)G>A.Glucocorticoid therapy(methylprednisolone pulse therapy or oral prednisone)and immunosuppressive agents(tacrolimus)had no effect.During a 3-year follow-up after genetic diagnosis by WES,proteinuria persisted,but the patient was healthy.CONCLUSION CRB2 mutations related to SRNS often occur in exons 7,10,and 12.Clinical manifestations of SRNS caused by CRB2 mutations are often less severe than in other forms of SRNS.展开更多
BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,pa...BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,particularly in children.This report describes a DPB case resolved with long-term azithromycin therapy,em-phasizing the need for a timely and accurate diagnosis.CASE SUMMARY A 12-year-old girl,diagnosed with asthma at age five and managed with inhaled corticosteroids and long-acting beta-2 agonists,developed a history of chronic productive cough and chronic sinusitis for a year.On examination,she exhibited wheezing and coarse crackles.Despite receiving treatment for an asthma exacer-bation,her symptoms did not improve.A chest X-ray revealed reticulonodular infiltration in both lower lungs,prompting further evaluation with high-resolu-tion computed tomography(HRCT).The HRCT confirmed centrilobular nodule opacities,a'tree-in-bud'pattern,and non-tapering bronchi,suggesting DPB.Elevated cold hemagglutinin titers at 128 further supported the diagnosis.Her cough and sinusitis resolved within a month after starting azithromycin therapy,chosen for its anti-inflammatory and immunomodulatory effects.Follow-up HRCT scans after 1 year of continuous treatment showed complete normalization.CONCLUSION This case highlights the importance of early diagnosis and prompt treatment in achieving favorable outcomes for DPB.展开更多
BACKGROUND The relationship between diabetes mellitus(DM)and asthma is complex and can impact disease trajectories.AIM To explore the bidirectional influences between the two conditions on clinical outcomes and diseas...BACKGROUND The relationship between diabetes mellitus(DM)and asthma is complex and can impact disease trajectories.AIM To explore the bidirectional influences between the two conditions on clinical outcomes and disease control.METHODS We systematically reviewed the literature on the relationship between DM and asthma,focusing on their impacts,mechanisms,and therapeutic implications.Various studies were assessed,which investigated the effect of glycemic control on asthma outcomes,lung function,and exacerbations.The study highlighted the role of specific diabetes medications in managing asthma.RESULTS The results showed that poor glycemic control in diabetes can exacerbate asthma,increase hospitalizations,and reduce lung function.Conversely,severe asthma,especially in obese individuals,can complicate diabetes management and make glycemic control more difficult.The diabetes-associated mechanisms,such as inflammation,microangiopathy,and oxidative stress,can exacerbate asthma and decrease lung function.Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations.CONCLUSION The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes.Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes,while asthma severity,especially in obese individuals,complicates diabetes control.However,the current research has limitations,and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.展开更多
The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response t...The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response to airborne irritants,this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea,cough,wheezing,and chest tightness.Conventional asthma therapies,such as corticosteroids,long-actingβ-agonists,and antiinflammatory agents,often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively.These limitations have prompted researchers to explore innovative therapeutic strategies,including stem cell-related interventions,offering hope to those afflicted with this incurable disease.In this review,we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.展开更多
Bronchial asthma is divided into type 2 and non-type 2 asthma based on the immunopathogenesis.Type 2 inflammation is an inflammation mediated by T helper 2 cells,group 2 innate lymphoid cells and sustained by a specif...Bronchial asthma is divided into type 2 and non-type 2 asthma based on the immunopathogenesis.Type 2 inflammation is an inflammation mediated by T helper 2 cells,group 2 innate lymphoid cells and sustained by a specific subset of cytokines.In recent years,type 2 asthma has become the research hotspot in the field of asthma.For type 2 asthma,targeted therapies have become effective treatments and widely used in clinical practice.In order to further understand the progress of biologic drugs for bronchial asthma,as well as the disease outcomes in patients with type 2 asthma,and improve asthma control and remission,this article reviewed the progress and achievements of biologic drugs for asthma from May 1,2023 to April 30,2024,providing clinical perspective for the choosing appropriate targeted treatment of asthma.It also highlights selected poster pre-sentations from the ATS 2024 Annual Meeting to provide clinical insights for choosing appropriate targeted treatments for Type 2 asthma.展开更多
Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compou...Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compounds and LD50 study of aqueous extract of A.sativum were achieved using standard biochemical methods.Twenty-four(24)male Wistar rats averagely weighing between 168–255 g were grouped into four of six animals in each steel-metal cage.Groups 1 and 2 served as normal and positive groups respectively.Rats in groups 2–4 were sensitized and challenged with a combination of OVA and LPS.Groups 3 and 4 were administered 250 and 500 mg/kg b.w of aqueous extract of A.sativum respectively for two weeks.The effect of aqueous extracts of A.sativum in OVA and LPS-induced asthma on alterations in differential white blood cells,inflammatory cytokines,some serum biochemical as well as histological indicators of experimental rats were assessed.Results:The aqueous extract of 600 g of plant material yielded 74.1 g accounting for 11.9%of sample material used.The result of the Phytochemical analysis showed higher number of glycosides,flavonoids and phenols.The animals displayed zero behavioral adverse reaction when administered the aqueous extract up to the highest dose of 5,000 mg/kg b.w.Administrations of aqueous extract of A.sativum remarkably(P<0.05;95%confidence intervals CI)declined the levels of neutrophils,eosinophils and total white blood cell count as opposed to the untreated group.Levels of interleukin 4(IL-4),interleukin 5(IL-5),interleukin 13(IL-13)and immunoglobulin E(IgE)of groups 3 and 4 had a significant(P<0.05;95%CI)varying percentage reduction(IL-4=39.78%,49.51%;IL-5=34.66%,40.05%;IL-13=31.96%,30.81%;33.45%,21.38%)respectively in comparison to group 2(untreated).The result showed a significantly(P<0.05,95%CI)declined malonaldehyde(MDA)concentration and elevated catalase,decreased glutathione concentration and superoxide dismutase activity of the treatment groups compared to the untreated.Serum liver function enzymes including alkaline phosphatase,alanine transaminase,and aspartate transaminase in the groups receiving aqueous extract of A.sativum exhibited a significant(P<0.05;95%CI)reduction in levels compared to group 2(untreated).Conclusion:Findings from this study indicated that aqueous extracts of A.sativum have the potential to improve asthma symptoms by decreasing inflammatory cytokines and mitigating oxidative stress.This effect could enhance the efficacy of conventional treatments such as inhaled corticosteroids,including cortisone,hydrocortisone,dexamethasone,and prednisone,as well as bronchodilators,leukotriene modifiers,and biologic therapies.Further studies need to be carried out on human subjects and also expanded to other respiratory disorders like Chronic obstructive pulmonary disease and Coronavirus Disease 2019.展开更多
The development of adrenergic agonists(AAs)for asthma has provided important mechanistic insights into acupuncture-based target discovery and treatment strategies.This review describes the historical evolution of AA t...The development of adrenergic agonists(AAs)for asthma has provided important mechanistic insights into acupuncture-based target discovery and treatment strategies.This review describes the historical evolution of AA therapy,including the precise optimization of nonselective toβ2-selective agonists,im-provement from short-acting to ultra-long-acting agents,shift from targeted monotherapy to combination regimens,and alterations in drug formulation.Additionally,this review summarizes recent advances in acupuncture treatment for asthma,including the development of novel targeted therapies,application of acupuncture-based combination regimens,and optimization of the mode of administration.Taken to-gether,this article discusses key insights from research on AA that inform acupuncture approaches,with a focus on:(1)precision targeting:identifying acupuncture-specific targets to improve efficacy;(2)syn-ergistic treatment:employing multi-target combination regimens to enhance therapeutic outcomes;(3)formulation innovation:advancing acupuncture delivery methods to improve patient compliance;and(4)evidence-based development:strengthening clinical research to generate high-quality evidence to inform the discovery of novel targets and treatment strategies for asthma.展开更多
Objective Asthma imposes a significant global health burden.This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios.Methods Usi...Objective Asthma imposes a significant global health burden.This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios.Methods Using data from the Global Burden of Disease 2021 study,we analyzed asthma incidence,prevalence,mortality,and disability-adjusted life years(DALYs)from 1990 to 2021.We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled.Temporal trends in age-standardized incidence,prevalence,mortality,and DALY rates were explored using Annual Percent Change.Results In 2021,the age-standardized rates for asthma incidence,prevalence,mortality,and DALYs in China were 364.17 per 100,000(95%uncertainty interval[UI]:283.22-494.10),1,956.49 per 100,000(95%UI:1,566.68-2,491.87),1.47 per 100,000(95%UI:1.15-1.79),and 103.76 per 100,000(95%UI:72.50-145.46),respectively.A higher disease burden was observed among Chinese men and individuals aged 70 years or older.Compared to the current trend,a combined scenario involving improvements in environmental factors,behavioral and metabolic health,child nutrition,and vaccination resulted in a greater reduction in the disease burden caused by asthma.Conclusion Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.展开更多
In China,omalizumab is indicated for patients with moderate to severe persistent allergic asthma in whom symptoms remain inadequately controlled despite treatment with inhaled corticosteroids(ICS)in combination with l...In China,omalizumab is indicated for patients with moderate to severe persistent allergic asthma in whom symptoms remain inadequately controlled despite treatment with inhaled corticosteroids(ICS)in combination with long actingβ-agonists(LABA)(GINA step 3 or higher),and urticaria.We report a case of joint and Achilles tendon inflammatory reactions in a patient with Th2-type asthma receiving omalizumab treatment.An adult male presented with recurrent episodes of sneezing,rhinorrhea,wheezing,chest tightness,shortness of breath,and dyspnea.He exhibited allergies to multiple substances and demonstrated impaired lung function,ultimately being diagnosed with allergic rhinitis and asthma.Following initial treatment with ICS and LABA,his symptoms were initially controlled.However,as the disease progressed,the frequency of nocturnal attacks increased,and the incidence of attacks during the allergy season escalated,leading to a significant decline in lung function.Subsequently,he commenced subcutaneous injections of omalizumab at a dosage of 600 mg monthly.There was a partial improvement in the frequency of asthma attacks after two injections.Unfortunately,four days after the first treatment,he reported pain in the right Achilles tendon.Rheumatological screenings,including a five-item antinuclear antibody test and an 11-item autoantibody profile test,revealed no significant abnormalities.Ankle joint ultrasound indicated hyperechoic spots around the Achilles tendon with acoustic shadows,suggesting the presence of Achilles tendinopathy.Ten days later,the pain symptoms resolved spontaneously.Due to the sig-nificant improvement in asthma symptoms,omalizumab treatment continued,albeit with a dosage reduction to 300mg.After intermittent treatment over four sessions,asthma symptoms improved markedly,with the Asthma Control Test(ACT)score increasing from 14 to 20.Lung function improved from moderate obstruction to mild obstruction.The only drawback was the patient’s recurrent swelling,pain,and joint effusion in the joints(specifically the knee and ankle)during the treatment period.Omalizumab is an effective therapeutic option for the treatment of allergic asthma.Although the incidence of adverse events reported in current studies is low,there have been emerging reports of joint swelling,pain,and myalgia reactions in both children and adults receiving treatment for asthma and urticaria.Given the rarity and non-specific nature of these reactions,it is challenging to ascertain the true incidence rate.Previous reports have described symptoms that occur upon initiation of the medication,which can recur upon re-administration.While the factors that may increase the risk of joint inflammatory reactions to omalizumab remain to be elucidated,this case contributes to a deeper understanding of this adverse reaction associated with a well-tolerated and important therapeutic agent.展开更多
Objective:To analyze the clinical value of Pulmicort Respules inhalation combined with cetirizine in the treatment of pediatric asthma.Methods:From December 2023 to December 2024,82 children with asthma admitted to ou...Objective:To analyze the clinical value of Pulmicort Respules inhalation combined with cetirizine in the treatment of pediatric asthma.Methods:From December 2023 to December 2024,82 children with asthma admitted to our hospital were randomly divided into a control group and an observation group,with 41 cases in each group.The clinical symptom relief time(shortness of breath,cough,dyspnea,lung wheezing),lung function indicators(FEV1,FVC,FEV1/FVC),inflammatory indicators(TNF-α,IL-6,IL-8),and clinical treatment effects were analyzed in the two groups.Results:The relief time for shortness of breath,cough,dyspnea,and lung wheezing in the observation group was shorter than that in the control group(P<0.05).After treatment,compared with the control group,the levels of FEV1,FVC,FEV1/FVC,and treatment efficiency in the observation group were higher,while the levels of TNF-α,IL-6,and IL-8 were lower(P<0.05).Conclusion:The combination of Pulmicort Respules inhalation and cetirizine oral therapy for children with asthma can shorten the improvement time of clinical symptoms,inhibit inflammation,and improve lung function.展开更多
Salvia miltiorrhiza(S.miltiorrhiza)represents a crucial component of traditional Chinese medicine,demonstrating effects on blood circulation activation and stasis removal,and has been widely utilized in asthma treatme...Salvia miltiorrhiza(S.miltiorrhiza)represents a crucial component of traditional Chinese medicine,demonstrating effects on blood circulation activation and stasis removal,and has been widely utilized in asthma treatment.This study isolated a novel phenolic acid(S1)from S.miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time.An allergic asthma(AA)model was established using ovalbumin(OVA).The mechanism of S1's effects on AA was investigated using multi-factor joint analysis,flow cytometry,and co-culture systems to facilitate clinical asthma treatment.S1(10 or 20 mg·kg-1)was administered daily to mice with OVA-induced AA(OVA-AA)during days 21-25.The study examined airway responsiveness,lung damage,inflammation,and levels of immunoglobulin E(IgE),PGD2,interleukins(IL-4,5,10,13,17A),tumor necrosis factorα(TNF-α),GM-CSF,CXCL1,CCL11,and mMCP-1.Additionally,mast cell(MC)activation and degranulation were explored,along with T helper type 17(Th17)/Treg immune cells and TLR4 pathway biomarkers.The antagonistic activity of that specific antagonist of TLR4(TAK-242)(1μmol·L^(-1)),a specific TLR4 blocker,against S1(10μmol·L^(-1))was examined in co-cultured 16 HBE cells and bone marrow-derived cells(BMDCs)or splenic lymphocytes(SLs)induced with LPS(1μg·mL^(-1))to elucidate the TLR4 pathway's mediating role.S1 demonstrated reduced airway responsiveness,lung damage,and inflammation,with downregulation of IgE,PGD2,interleukins,TNF-α,GM-CSF,CXCL1,CCL11,and mMCP-1.It also impeded MC activation and degranulation,upregulated IL^(-1)0,and influenced Th17/Treg immune cell transformation following OVA challenge.Furthermore,S1 inhibited the TLR4 pathway in OVA-AA mice,and TLR4 antagonism enhanced S1's positive effects.Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms,restores lung function,and inhibits airway response.S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation,attributable at least partially to the TLR4 pathway.This study provides molecular justification for S1 in AA treatment.展开更多
BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventio...BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.展开更多
The symptoms of allergic airway disease are impacted by the interplay of gut microbiota,which may be modulated by probiotics.This study aimed to investigate the potential anti-inflammatory effects of three lactic acid...The symptoms of allergic airway disease are impacted by the interplay of gut microbiota,which may be modulated by probiotics.This study aimed to investigate the potential anti-inflammatory effects of three lactic acid bacteria(LAB)on allergic asthma through modulation of the gut microbiota.Ovalbumin(OVA)-induced asthmatic mice were treated with three LAB strains,and their gut microbiota profiles were analyzed using 16S rRNA sequencing.Fecal microbiota transplantation(FMT)from mice fed with Lactobacillus rhamnosus RL-H3-005 was administered to OVA-induced asthmatic mice.The results demonstrated that RL-H3-005 effectively reduced inflammatory infiltrates in the lung and colon,as well as suppressed cytokine levels associated with allergic asthma compared to other strains.In addition,the supplementation of RL-H3-005 modulated the composition of gut microbiota in mice with allergic asthma.FMT results further supported the notion that modulating the gut microbiota with RL-H3-005 plays a crucial role in attenuating airway inflammatory symptoms in allergic asthma.展开更多
OBJECTIVE:To summarize the clinical efficacy characteristics of Suhuang Zhike capsule(苏黄止咳颗粒)and evaluate the incidence of adverse reactions in its broad clinical application.METHODS:This was a multicenter,prosp...OBJECTIVE:To summarize the clinical efficacy characteristics of Suhuang Zhike capsule(苏黄止咳颗粒)and evaluate the incidence of adverse reactions in its broad clinical application.METHODS:This was a multicenter,prospective,singlearm,open-label phase IV clinical trial.A total of 1100 patients diagnosed with cough variant asthma(CVA)and the Traditional Chinese Medicine(TCM)syndrome of wind evil invading the lung and lung Qi failing to propagate were planned for recruitment.Participants received Suhuang Zhike capsule orally,three capsules per dose,taken three times daily,for a treatment duration of 14 d.The primary outcome was the change in cough symptom scores from baseline to week 2.Cough severity was assessed twice daily.Additional evaluations included the rate and time of cough disappearance or basic disappearance rate,as well as the time of cough relief.TCM symptom scores were recorded at baseline and on days 7 and 14 of treatment.Safety assessments included monitoring for adverse events and conducting laboratory tests.RESULTS:A total of 1033 patients with CVA from 40 hospitals across China were enrolled in the study.Of these,1026 patients received the study medication and were included in the safety analysis.Fifty-four patients withdrew from the study,resulting in a drop-out rate of 5.23%.Treatment with Suhuang Zhike capsules significantly reduced cough symptom scores and improved cough-related symptoms in patients with CVA.The overall rate of cough disappearance or basic disappearance increased over the course of treatment,reaching 67.21%after 14 d.The median time of cough relief was 3 d,while the median time to cough disappearance or basic disappearance was 11 d.Additionally,the treatment led to reductions in TCM symptom scores and improvements in accompanying symptoms such as throat itching,expectoration,and shortness of breath.In terms of safety,no serious adverse events were reported.The incidence of related adverse events(AEs)was 2.24%(23 cases,30 events).The incidence of adverse reactions listed in the drug's instructions was 2.14%.Other related AEs not listed in the drug's instructions occurred in 0.39%of patients and included dizziness(0.19%),headache(0.10%),pruritus(0.10%),and palpitation(0.10%).CONCLUSION:Suhuang Zhike capsules demonstrated good efficacy and safety for the treatment of CVA.These findings offer valuable clinical evidence to support their broader application in routine clinical practice.展开更多
BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilit...BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81070026）, the Key Project of Hunan Provincial Science and Technology Department （No. 2012FJ4375）, and the Open Innovation Platform of Hunan College （No. 10K076）.
文摘Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats were less sensitive to DXM treatment.Anti-HMGB1 treatment attenuated airway hyperresponsiveness,inflammation,and remodeling in SRA rats to a certain extent and was accompanied by lower levels of IL-17 （（369.2±126.7） vs.（780.5±261.7） pg/ml in control SRA rats） in BALF （P ＜0.05）.Low-intensity aerobic exercise training decreased the expression of both HMGB1 （（14.1±2.9） vs.（21.2±4.5） ng/ml in control SRA rats） and IL-17 （（545.3±148.6） vs.（780.5±261.7） pg/ml in control SRA rats） in BALF （all P ＜0.05） and was accompanied by improved airway hyperresponsiveness,inflammation,and remodeling in SRA rats （all P ＜0.05）.Conclusions Low-intensity aerobic exercise training attenuated airway hyperresponsiveness,inflammation,and remodeling in a rat model of SPA.Decreased HMGB1 and IL-17 levels in BALF by aerobic exercise training at least partly contributed to the improvements of SPA.
基金This work was supported by the Guangdong Basic and Applied Ba-sic Research Foundation(No.2020B1515020004)the National Natural Science Foundation of China(No.81873404)+1 种基金Project of Young Inno-vative Talents in Colleges and Universities in Guangdong Province(No.2018KQNCX095)Affiliated Hospital of Guangdong Medical University Clinical Research Program(Nos.LCYJ2018C001,LCYJ2019B011).
文摘Steroid resistance represents a major clinical problem in the treatment of severe asthma,and therefore a better understanding of its pathogenesis is warranted.Recent studies indicated that histone deacetylase 2(HDAC2)and interleukin 17A(IL-17A)play important roles in severe asthma.HDAC2 activity is reduced in patients with severe asthma and smoking-induced asthma,perhaps accounting for the amplified expression of inflammatory genes,which is associated with increased acetylation of glucocorticoid receptors.Neutrophilic inflammation contributes to severe asthma and may be related to T helper(Th)17 rather than Th2 cytokines.IL-17A levels are elevated in severe asthma and correlate with the presence of neutrophils.Restoring the activity of HDAC2 or targeting the Th17 signaling pathway is a potential therapeutic approach to reverse steroid insensitivity.
基金Supported by the Hainan Provincial Natural Science Foundation of China(No.825RC898)Hainan Province Clinical Medical Center。
文摘AIM:To comprehensively assess the relationship between asthma and myopia based on the National Health and Nutrition Examination Survey(NHANES)database combined with Mendelian randomization(MR).METHODS:Initially,20497 subjects from the complete questionnaire cycle in the NHANES database from 2005 to 2008 were included.By exclusion criteria,8460 subjects were screened with 1676 myopia samples and 6784 control samples.Subsequently,baseline characteristics,association analyses,risk stratification analyses,and receive operating characteristic curve(ROC)were used to investigate the associations between covariates and myopia.Then,the causal relationship was explored in depth by MR analysis,and was estimated the reliability by sensitivity analyses and directionality tests.RESULTS:Baseline characteristics illustrated a significant difference between myopia and controls for both asthma and covariates(excluding gender;P<0.05).The results in all three models indicated that asthma was strongly associated with myopia and the effect on myopia was not significantly confounded by other covariates[model 3:odd ratio(OR)=1.31;95%CI=1.07-1.62;P=0.0133].The risk stratification analysis again verified that asthma remained strongly associated with myopia and was a risk factor for myopia(P<0.05,OR>1).ROC proved that the model was accurate in its prediction[area under curve(AUC)=0.7].Subsequently,the causal relationship between them was statistically significant(P<0.05)according to the inverse variance weighted(IVW)method in MR.Scatterplot showed that asthma and myopia had significant positive causality and were not affected by confounders.Forest plot displayed an increasing risk of myopia on asthma(OR>1).The funnel plot demonstrated compliance with Mendel’s second law.Sensitivity analysis and directional analysis further confirmed the confidence of the MR analysis results and a unidirectional causal relationship between them.CONCLUSION:A significant association and causality between asthma and myopia is found through the NHANES database and MR analysis,which is important implications for public health policy development and clinical practice.
文摘Objective: To observe the clinical efficacy and safety of low dose tacrolimus (TAC) combined with tripterygium (TW) in treatment of steroid resistant nephritic syndrome (SRNS). Method: The patients, who were diagnosed with mesangial proliferative glomerulonephritis (MesPGN) and focal segmental glomerulosclerosis (FSGS) by biopsy and failed to respond to a 3-month treatment with prednisone (1 mg/kg·d), were randomly divided into 2 groups (TAC + TW Group and TW Group). Initially TAC + TW group took TAC 0.05mg/(kg·d) 2 h after meal at 12 h interval. The plasma TAC level was examined after 3 days and was kept at 1.5 - 4 ng·ml;meanwhile, TW was given at 60 mg/d before meal. TW group only took TW (60 mg/d). The efficacy, adverse reactions and plasma TAC levels were observed in each group. Results: 1) Totally 20 SRNS patients completed the trial, 11 of TAC + TW Group and 9 of TW Group. There is no statistical difference between the two groups in terms of age, gender, duration since onset of the disease, blood pressure, 24 h UPQ, serum albumin, creatinine, cholesterol, triglyceride, FBG, kidney pathological categories, time of taking prednisone etc.;2) Urine protein started to decrease after 1 month treatment in both of TAC + TW and TW groups. By the 12th month of treatment, TAC + TW group showed 8 cases of complete remission (72.7%), 2 cases of partial remission (18.2%) and 1 case of no improvement (9.1%), while those of TW groups were 2 (22.2%), 4 (44.5%) and 3 (33.3%), respectively;3) With treatment, the TAC + TW Group patients’ plasma protein was significantly higher than that of pretreatment stage and recovered to normal level after 6 month of treatment. However, there was no significant plasma protein increase in TW Group. No obvious changes were observed on serum creatinine level of patients of both the two groups;4) The incidence of adverse reactions was not significantly different between the two groups. Conclusion: TAC + TW reduced proteinuria of SRNS patients, increased clinical remission rate and was tolerant to SRNS patients. We conclude that TAC + TW treatment is an effective way to treat patients with SRNS.
文摘Objective:?Although several NPHS2 gene mutations and polymorphisms were described and?associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS),?the?occurrence of these genetic abnormalities or variants appeared?to be influenced by race and ethnic group. We have investigated?probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children?with primary SRNS?whovisited?the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were?conducted through screenings?for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing.?Fisher’s Exact Test was used to determine?the?correlation?between?NPHS2 polymorphisms and clinical manifestations.Results:?Seven?females (25%) and 21 males (75%)?participated in the study.?The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg.?We identified 6 NPHS2polymorphisms,?i.e.?g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation?was found. There was?no correlation?between?NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The?results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.
文摘BACKGROUND Crumbs homolog 2(CRB2)is a recently discovered gene that is closely related to the maintenance of normal polarity in podocytes;mutations can directly lead to steroid-resistant nephrotic syndrome(SRNS).However,the characteristics of nephrotic syndrome(NS)caused by CRB2 mutations have not been described.CASE SUMMARY We report a novel compound heterozygous mutation of the CRB2 gene in two siblings with SRNS.The two siblings had edema,proteinuria,hypoproteinemia and hyperlipidemia.Both their father and mother had normal phenotypes(no history of NS).Whole exon sequencing(WES)of the family showed a novel compound heterozygous mutation,c.2290(exon 8)C>T and c.3613(exon 12)G>A.Glucocorticoid therapy(methylprednisolone pulse therapy or oral prednisone)and immunosuppressive agents(tacrolimus)had no effect.During a 3-year follow-up after genetic diagnosis by WES,proteinuria persisted,but the patient was healthy.CONCLUSION CRB2 mutations related to SRNS often occur in exons 7,10,and 12.Clinical manifestations of SRNS caused by CRB2 mutations are often less severe than in other forms of SRNS.
文摘BACKGROUND Diffuse panbronchiolitis(DPB)is a rare,chronic inflammatory lung disease mar-ked by chronic cough,breathlessness,and preceding sinusitis.Symptoms often persist for years and can be misdiagnosed as asthma,particularly in children.This report describes a DPB case resolved with long-term azithromycin therapy,em-phasizing the need for a timely and accurate diagnosis.CASE SUMMARY A 12-year-old girl,diagnosed with asthma at age five and managed with inhaled corticosteroids and long-acting beta-2 agonists,developed a history of chronic productive cough and chronic sinusitis for a year.On examination,she exhibited wheezing and coarse crackles.Despite receiving treatment for an asthma exacer-bation,her symptoms did not improve.A chest X-ray revealed reticulonodular infiltration in both lower lungs,prompting further evaluation with high-resolu-tion computed tomography(HRCT).The HRCT confirmed centrilobular nodule opacities,a'tree-in-bud'pattern,and non-tapering bronchi,suggesting DPB.Elevated cold hemagglutinin titers at 128 further supported the diagnosis.Her cough and sinusitis resolved within a month after starting azithromycin therapy,chosen for its anti-inflammatory and immunomodulatory effects.Follow-up HRCT scans after 1 year of continuous treatment showed complete normalization.CONCLUSION This case highlights the importance of early diagnosis and prompt treatment in achieving favorable outcomes for DPB.
文摘BACKGROUND The relationship between diabetes mellitus(DM)and asthma is complex and can impact disease trajectories.AIM To explore the bidirectional influences between the two conditions on clinical outcomes and disease control.METHODS We systematically reviewed the literature on the relationship between DM and asthma,focusing on their impacts,mechanisms,and therapeutic implications.Various studies were assessed,which investigated the effect of glycemic control on asthma outcomes,lung function,and exacerbations.The study highlighted the role of specific diabetes medications in managing asthma.RESULTS The results showed that poor glycemic control in diabetes can exacerbate asthma,increase hospitalizations,and reduce lung function.Conversely,severe asthma,especially in obese individuals,can complicate diabetes management and make glycemic control more difficult.The diabetes-associated mechanisms,such as inflammation,microangiopathy,and oxidative stress,can exacerbate asthma and decrease lung function.Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations.CONCLUSION The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes.Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes,while asthma severity,especially in obese individuals,complicates diabetes control.However,the current research has limitations,and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.
基金the Joint Innovation Project Funds of Huaqiao University,No.2022YX001.
文摘The global incidence of asthma,a leading respiratory disorder affecting more than 235 million people,has dramatically increased in recent years.Characterized by chronic airway inflammation and an imbalanced response to airborne irritants,this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea,cough,wheezing,and chest tightness.Conventional asthma therapies,such as corticosteroids,long-actingβ-agonists,and antiinflammatory agents,often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively.These limitations have prompted researchers to explore innovative therapeutic strategies,including stem cell-related interventions,offering hope to those afflicted with this incurable disease.In this review,we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.
基金supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-049)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0529800).
文摘Bronchial asthma is divided into type 2 and non-type 2 asthma based on the immunopathogenesis.Type 2 inflammation is an inflammation mediated by T helper 2 cells,group 2 innate lymphoid cells and sustained by a specific subset of cytokines.In recent years,type 2 asthma has become the research hotspot in the field of asthma.For type 2 asthma,targeted therapies have become effective treatments and widely used in clinical practice.In order to further understand the progress of biologic drugs for bronchial asthma,as well as the disease outcomes in patients with type 2 asthma,and improve asthma control and remission,this article reviewed the progress and achievements of biologic drugs for asthma from May 1,2023 to April 30,2024,providing clinical perspective for the choosing appropriate targeted treatment of asthma.It also highlights selected poster pre-sentations from the ATS 2024 Annual Meeting to provide clinical insights for choosing appropriate targeted treatments for Type 2 asthma.
文摘Background:To appraise the ameliorative potentials of Allium sativum aqueous extract in ovalbumin(OVA)-lipopolysaccharide(LPS)-induced asthma.Methods:Extraction,phytochemical analysis,determination of bioactive compounds and LD50 study of aqueous extract of A.sativum were achieved using standard biochemical methods.Twenty-four(24)male Wistar rats averagely weighing between 168–255 g were grouped into four of six animals in each steel-metal cage.Groups 1 and 2 served as normal and positive groups respectively.Rats in groups 2–4 were sensitized and challenged with a combination of OVA and LPS.Groups 3 and 4 were administered 250 and 500 mg/kg b.w of aqueous extract of A.sativum respectively for two weeks.The effect of aqueous extracts of A.sativum in OVA and LPS-induced asthma on alterations in differential white blood cells,inflammatory cytokines,some serum biochemical as well as histological indicators of experimental rats were assessed.Results:The aqueous extract of 600 g of plant material yielded 74.1 g accounting for 11.9%of sample material used.The result of the Phytochemical analysis showed higher number of glycosides,flavonoids and phenols.The animals displayed zero behavioral adverse reaction when administered the aqueous extract up to the highest dose of 5,000 mg/kg b.w.Administrations of aqueous extract of A.sativum remarkably(P<0.05;95%confidence intervals CI)declined the levels of neutrophils,eosinophils and total white blood cell count as opposed to the untreated group.Levels of interleukin 4(IL-4),interleukin 5(IL-5),interleukin 13(IL-13)and immunoglobulin E(IgE)of groups 3 and 4 had a significant(P<0.05;95%CI)varying percentage reduction(IL-4=39.78%,49.51%;IL-5=34.66%,40.05%;IL-13=31.96%,30.81%;33.45%,21.38%)respectively in comparison to group 2(untreated).The result showed a significantly(P<0.05,95%CI)declined malonaldehyde(MDA)concentration and elevated catalase,decreased glutathione concentration and superoxide dismutase activity of the treatment groups compared to the untreated.Serum liver function enzymes including alkaline phosphatase,alanine transaminase,and aspartate transaminase in the groups receiving aqueous extract of A.sativum exhibited a significant(P<0.05;95%CI)reduction in levels compared to group 2(untreated).Conclusion:Findings from this study indicated that aqueous extracts of A.sativum have the potential to improve asthma symptoms by decreasing inflammatory cytokines and mitigating oxidative stress.This effect could enhance the efficacy of conventional treatments such as inhaled corticosteroids,including cortisone,hydrocortisone,dexamethasone,and prednisone,as well as bronchodilators,leukotriene modifiers,and biologic therapies.Further studies need to be carried out on human subjects and also expanded to other respiratory disorders like Chronic obstructive pulmonary disease and Coronavirus Disease 2019.
基金Supported by National Natural Science Foundation of China:No.82374583,82274646.
文摘The development of adrenergic agonists(AAs)for asthma has provided important mechanistic insights into acupuncture-based target discovery and treatment strategies.This review describes the historical evolution of AA therapy,including the precise optimization of nonselective toβ2-selective agonists,im-provement from short-acting to ultra-long-acting agents,shift from targeted monotherapy to combination regimens,and alterations in drug formulation.Additionally,this review summarizes recent advances in acupuncture treatment for asthma,including the development of novel targeted therapies,application of acupuncture-based combination regimens,and optimization of the mode of administration.Taken to-gether,this article discusses key insights from research on AA that inform acupuncture approaches,with a focus on:(1)precision targeting:identifying acupuncture-specific targets to improve efficacy;(2)syn-ergistic treatment:employing multi-target combination regimens to enhance therapeutic outcomes;(3)formulation innovation:advancing acupuncture delivery methods to improve patient compliance;and(4)evidence-based development:strengthening clinical research to generate high-quality evidence to inform the discovery of novel targets and treatment strategies for asthma.
文摘Objective Asthma imposes a significant global health burden.This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios.Methods Using data from the Global Burden of Disease 2021 study,we analyzed asthma incidence,prevalence,mortality,and disability-adjusted life years(DALYs)from 1990 to 2021.We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled.Temporal trends in age-standardized incidence,prevalence,mortality,and DALY rates were explored using Annual Percent Change.Results In 2021,the age-standardized rates for asthma incidence,prevalence,mortality,and DALYs in China were 364.17 per 100,000(95%uncertainty interval[UI]:283.22-494.10),1,956.49 per 100,000(95%UI:1,566.68-2,491.87),1.47 per 100,000(95%UI:1.15-1.79),and 103.76 per 100,000(95%UI:72.50-145.46),respectively.A higher disease burden was observed among Chinese men and individuals aged 70 years or older.Compared to the current trend,a combined scenario involving improvements in environmental factors,behavioral and metabolic health,child nutrition,and vaccination resulted in a greater reduction in the disease burden caused by asthma.Conclusion Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
文摘In China,omalizumab is indicated for patients with moderate to severe persistent allergic asthma in whom symptoms remain inadequately controlled despite treatment with inhaled corticosteroids(ICS)in combination with long actingβ-agonists(LABA)(GINA step 3 or higher),and urticaria.We report a case of joint and Achilles tendon inflammatory reactions in a patient with Th2-type asthma receiving omalizumab treatment.An adult male presented with recurrent episodes of sneezing,rhinorrhea,wheezing,chest tightness,shortness of breath,and dyspnea.He exhibited allergies to multiple substances and demonstrated impaired lung function,ultimately being diagnosed with allergic rhinitis and asthma.Following initial treatment with ICS and LABA,his symptoms were initially controlled.However,as the disease progressed,the frequency of nocturnal attacks increased,and the incidence of attacks during the allergy season escalated,leading to a significant decline in lung function.Subsequently,he commenced subcutaneous injections of omalizumab at a dosage of 600 mg monthly.There was a partial improvement in the frequency of asthma attacks after two injections.Unfortunately,four days after the first treatment,he reported pain in the right Achilles tendon.Rheumatological screenings,including a five-item antinuclear antibody test and an 11-item autoantibody profile test,revealed no significant abnormalities.Ankle joint ultrasound indicated hyperechoic spots around the Achilles tendon with acoustic shadows,suggesting the presence of Achilles tendinopathy.Ten days later,the pain symptoms resolved spontaneously.Due to the sig-nificant improvement in asthma symptoms,omalizumab treatment continued,albeit with a dosage reduction to 300mg.After intermittent treatment over four sessions,asthma symptoms improved markedly,with the Asthma Control Test(ACT)score increasing from 14 to 20.Lung function improved from moderate obstruction to mild obstruction.The only drawback was the patient’s recurrent swelling,pain,and joint effusion in the joints(specifically the knee and ankle)during the treatment period.Omalizumab is an effective therapeutic option for the treatment of allergic asthma.Although the incidence of adverse events reported in current studies is low,there have been emerging reports of joint swelling,pain,and myalgia reactions in both children and adults receiving treatment for asthma and urticaria.Given the rarity and non-specific nature of these reactions,it is challenging to ascertain the true incidence rate.Previous reports have described symptoms that occur upon initiation of the medication,which can recur upon re-administration.While the factors that may increase the risk of joint inflammatory reactions to omalizumab remain to be elucidated,this case contributes to a deeper understanding of this adverse reaction associated with a well-tolerated and important therapeutic agent.
文摘Objective:To analyze the clinical value of Pulmicort Respules inhalation combined with cetirizine in the treatment of pediatric asthma.Methods:From December 2023 to December 2024,82 children with asthma admitted to our hospital were randomly divided into a control group and an observation group,with 41 cases in each group.The clinical symptom relief time(shortness of breath,cough,dyspnea,lung wheezing),lung function indicators(FEV1,FVC,FEV1/FVC),inflammatory indicators(TNF-α,IL-6,IL-8),and clinical treatment effects were analyzed in the two groups.Results:The relief time for shortness of breath,cough,dyspnea,and lung wheezing in the observation group was shorter than that in the control group(P<0.05).After treatment,compared with the control group,the levels of FEV1,FVC,FEV1/FVC,and treatment efficiency in the observation group were higher,while the levels of TNF-α,IL-6,and IL-8 were lower(P<0.05).Conclusion:The combination of Pulmicort Respules inhalation and cetirizine oral therapy for children with asthma can shorten the improvement time of clinical symptoms,inhibit inflammation,and improve lung function.
基金supported by the National Natural Science Foundation of China(No.32200322)Henan Science and Technology Research and Development Plan Joint Fund(No.242301420082)+1 种基金Henan Province“Science and Technology Vice General”Three-Year Action Plan(2024-2026)Henan Postdoctoral Fund(No.HN2025059)。
文摘Salvia miltiorrhiza(S.miltiorrhiza)represents a crucial component of traditional Chinese medicine,demonstrating effects on blood circulation activation and stasis removal,and has been widely utilized in asthma treatment.This study isolated a novel phenolic acid(S1)from S.miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time.An allergic asthma(AA)model was established using ovalbumin(OVA).The mechanism of S1's effects on AA was investigated using multi-factor joint analysis,flow cytometry,and co-culture systems to facilitate clinical asthma treatment.S1(10 or 20 mg·kg-1)was administered daily to mice with OVA-induced AA(OVA-AA)during days 21-25.The study examined airway responsiveness,lung damage,inflammation,and levels of immunoglobulin E(IgE),PGD2,interleukins(IL-4,5,10,13,17A),tumor necrosis factorα(TNF-α),GM-CSF,CXCL1,CCL11,and mMCP-1.Additionally,mast cell(MC)activation and degranulation were explored,along with T helper type 17(Th17)/Treg immune cells and TLR4 pathway biomarkers.The antagonistic activity of that specific antagonist of TLR4(TAK-242)(1μmol·L^(-1)),a specific TLR4 blocker,against S1(10μmol·L^(-1))was examined in co-cultured 16 HBE cells and bone marrow-derived cells(BMDCs)or splenic lymphocytes(SLs)induced with LPS(1μg·mL^(-1))to elucidate the TLR4 pathway's mediating role.S1 demonstrated reduced airway responsiveness,lung damage,and inflammation,with downregulation of IgE,PGD2,interleukins,TNF-α,GM-CSF,CXCL1,CCL11,and mMCP-1.It also impeded MC activation and degranulation,upregulated IL^(-1)0,and influenced Th17/Treg immune cell transformation following OVA challenge.Furthermore,S1 inhibited the TLR4 pathway in OVA-AA mice,and TLR4 antagonism enhanced S1's positive effects.Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms,restores lung function,and inhibits airway response.S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation,attributable at least partially to the TLR4 pathway.This study provides molecular justification for S1 in AA treatment.
文摘BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.
文摘The symptoms of allergic airway disease are impacted by the interplay of gut microbiota,which may be modulated by probiotics.This study aimed to investigate the potential anti-inflammatory effects of three lactic acid bacteria(LAB)on allergic asthma through modulation of the gut microbiota.Ovalbumin(OVA)-induced asthmatic mice were treated with three LAB strains,and their gut microbiota profiles were analyzed using 16S rRNA sequencing.Fecal microbiota transplantation(FMT)from mice fed with Lactobacillus rhamnosus RL-H3-005 was administered to OVA-induced asthmatic mice.The results demonstrated that RL-H3-005 effectively reduced inflammatory infiltrates in the lung and colon,as well as suppressed cytokine levels associated with allergic asthma compared to other strains.In addition,the supplementation of RL-H3-005 modulated the composition of gut microbiota in mice with allergic asthma.FMT results further supported the notion that modulating the gut microbiota with RL-H3-005 plays a crucial role in attenuating airway inflammatory symptoms in allergic asthma.
基金Supported by the Inheritance and Innovation of Traditional Chinese Medicine"Hundred Million"Talent Project(Qihuang Project)(2019-QTL-003)。
文摘OBJECTIVE:To summarize the clinical efficacy characteristics of Suhuang Zhike capsule(苏黄止咳颗粒)and evaluate the incidence of adverse reactions in its broad clinical application.METHODS:This was a multicenter,prospective,singlearm,open-label phase IV clinical trial.A total of 1100 patients diagnosed with cough variant asthma(CVA)and the Traditional Chinese Medicine(TCM)syndrome of wind evil invading the lung and lung Qi failing to propagate were planned for recruitment.Participants received Suhuang Zhike capsule orally,three capsules per dose,taken three times daily,for a treatment duration of 14 d.The primary outcome was the change in cough symptom scores from baseline to week 2.Cough severity was assessed twice daily.Additional evaluations included the rate and time of cough disappearance or basic disappearance rate,as well as the time of cough relief.TCM symptom scores were recorded at baseline and on days 7 and 14 of treatment.Safety assessments included monitoring for adverse events and conducting laboratory tests.RESULTS:A total of 1033 patients with CVA from 40 hospitals across China were enrolled in the study.Of these,1026 patients received the study medication and were included in the safety analysis.Fifty-four patients withdrew from the study,resulting in a drop-out rate of 5.23%.Treatment with Suhuang Zhike capsules significantly reduced cough symptom scores and improved cough-related symptoms in patients with CVA.The overall rate of cough disappearance or basic disappearance increased over the course of treatment,reaching 67.21%after 14 d.The median time of cough relief was 3 d,while the median time to cough disappearance or basic disappearance was 11 d.Additionally,the treatment led to reductions in TCM symptom scores and improvements in accompanying symptoms such as throat itching,expectoration,and shortness of breath.In terms of safety,no serious adverse events were reported.The incidence of related adverse events(AEs)was 2.24%(23 cases,30 events).The incidence of adverse reactions listed in the drug's instructions was 2.14%.Other related AEs not listed in the drug's instructions occurred in 0.39%of patients and included dizziness(0.19%),headache(0.10%),pruritus(0.10%),and palpitation(0.10%).CONCLUSION:Suhuang Zhike capsules demonstrated good efficacy and safety for the treatment of CVA.These findings offer valuable clinical evidence to support their broader application in routine clinical practice.
基金Supported by the Joint Innovation Project Funds of Huaqiao University,No.2022YX001。
文摘BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.
