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Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.
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Objective:To study the the mechanism of action of Huanglong Mixture in the treatment of cough variant asthma (CVA) in children based on the IL-4/signal transduction and activator of transcription 6 (STAT6) signaling pathway using network pharmacology methods, molecular docking techniques, and in vitro cell experiments.Methods:The components and targets of various TCM components in Huanglong Mixture were searched in TCMSP database, HERB database and literature, and the disease targets of CVA were found in Gene Cards database, OMIM database, DrugBank database and PharmGkb database. The STRING database was used to construct the protein-protein interaction network, and Cytoscape 3.9.1 was used for topology analysis to screen out the core targets. The disease-drug-component-target network was constructed to screen out the core components. The KEGG enrichment analysis and GO enrichment analysis of the intersection targets were performed using Metascape software. PDB protein database, PubChem, Autodock and R language were used for molecular docking verification of core targets and core drug components. Finally, rat primary airway smooth muscle cells were cultured, modeled with interleukin-4 (IL-4), and p-STAT6 expression in the cytoplasm and nucleus was detected by Western blot.Results:A total of 122 effective components were obtained, including quercetin, kaempferol, luteolin and so on. The core targets included JUN, ESR1, TP53, MYC, HIF1, etc. GO enrichment analysis involved biological processes such as response to external stimuli, response to oxygen levels, positive regulation of protein phosphorylation, and regulation of cellular stress response. KEGG enrichment analysis showed that the main pathways of Huanglong Mixture in treating CVA included advanced glycation end product-glycation end product receptor (AGE-RAGE) signaling pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Janus kinase/signal transduction activation factor (JAK-STAT) signaling pathway. Molecular docking found that the core targets and core drug components had good combination. Cell experiments also confirmed that Huanglong Mixture could inhibit p-STAT6 entering the nucleus.Conclusions:The effective components and targets of Huanglong Mixture in the treatment of CVA are successfully predicted. The mechanism of Huanglong Mixture in the treatment of children with CVA may be related to the inhibition of IL-4/STAT6 signaling pathway.
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Objective:To evaluate the therapeutic effect of glycyrrhetinic acid on cough variant asthma (CVA) mice based on molecular docking technique; To explore the possibility of its treatment for cough variant asthma.Methods:The software of Autodock Vina was used for molecular docking. The mice were divided into control group, model group, prednisone acetate group, glycyrrhetinic acid high-, medium-, and low-dosage groups according to the random number table method, with 8 mice in each group. Except for the blank control group, all other groups were induced by egg protein to establish cough variant asthma models. Glycyrrhetinic acid high-, medium-, and low-dosage groups were orally administered glycyrrhetinic acid suspension at 20, 10, and 5 mg/kg, while the prednisone acetate group was orally administered prednisone acetate at 5 mg/kg. The blank control group and model group were orally administered equal volumes of physiological saline, once per day for 14 consecutive days. The animal asthma behavior was observed after drug administration. The secretion of bronchial mucus in lung tissue were observed by AB-PAS staining and the index of spleen were recorded. The protein expressions of Gata3, IL-4 and IL-13 in the spleen tissue were determined by Western blot.Results:Molecular docking results showed that glycyrrhetinic acid had good binding ability to Th2-related factors Gata3, IL-4 and IL-13. Results of animal experiment showed that compared with the model group, the mucus secretion decreased in glycyrrhetinic acid groups, the index of the spleen of mice obviously decreased, protein expression levels of IL-4 and IL-13 in the spleen tissue of mice in glycyrrhetinic acid high-, medium-, and low-dosage groups decreased ( P<0.05), and Gata3 in glycyrrhetinic acid medium- and low-dosage groups decreased ( P<0.05). Conclusion:Glycyrrhetinic acid can correct the shift of Th2 in the immune system of cough variant asthma mice and has a certain therapeutic effect.
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Objective To investigate the therapeutic effects and mechanisms of Maxing Shigan Decoction on cough variant asthma(CVA)rats.Methods Sixty rats were randomly divided into normal group,model group,low and high dose groups of Maxing Shigan Decoction,and high-dose of Maxing Shigan Decoction + signal transducer and activator of transcription 3(STAT3)activator Colivelin(Col)group,12 rats in each group.Except for the normal group,the CVA model was constructed by intraperitoneal injection of ovalbumin combined with moxa fumigation in all other groups of rats.After the corresponding treatment,the rats were observed for signs and cough counts,airway resistance(RE)was detected by pulmonary function meter,eosinophils(EOS)were counted by Diff-Quik staining,histopathological features of the lungs and bronchial tubes were observed by hematoxylin-eosin(HE)staining method,and the lung tissues were detected by enzyme-linked immunosorbent assay(ELISA)for monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α),and the protein expression levels of interleukin 6(IL-6),STAT3,and transient receptor potential vanilloid-1 channel(TRPV1)were detected by Western Blot.Results Compared with the normal group,rats in the model group showed obvious asthma symptoms,severe inflammatory cell infiltration was seen in the lung tissue,bronchial epithelial cell necrosis,ciliated adhesion,mucus,and RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,TRPV1 were elevated(P＜0.05);compared with the model group,rats in the low-and high-dose groups of Maxing Shigan Decoction showed significant improvement in asthma symptoms,reduction in lung and bronchial injury,and dose-dependent reduction in RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05);compared with the high-dose group of Maxing Shigan Decoction,the rats in the high-dose Maxing Shigan Decoction+Col group showed increased asthma,increased lung and bronchial injury,and increased RE,EOS number,MCP-1 and TNF-α contents,and protein expression levels of IL-6,STAT3,and TRPV1(P＜0.05).Conclusion Maxing Shigan Decoction can effectively improve cough variant asthma in rats,and its mechanism is related to the inhibition of IL-6/STAT3 signaling pathway and the high expression of TRPV1.
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Objective To explore the clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma(CVA)and its impact on serological indicators,airway function of children.Methods A total of 124 children with CVA admitted to the Zigong First People's Hospital from March 2019 to April 2022 were selected as the research subjects.The children were divided into control group and observation group according to random number table method,with 62 cases in each group.The children in the control group were treated with procaterol hydrochloride,and the children in the observation group were treated with procaterol hydrochloride and Xiaokechuan capsule for two weeks.The clinical efficacy of children was compared between the two groups after treatment.The cough scores during the day and night of children were evaluated in the two groups before and 2 weeks after treatment.The serum high mobility group protein B1(HMGB1),Toll like receptor 4(TLR4),nuclear factor-κB(NF-κB),interleukin-4(IL-4),interferon-γ(INF-γ)levels of children in the two groups were measured by enzyme linked immunosorbent assay before and 2 weeks after treatment,and the ratio of INF-γ/IL-was calculated.The 25％maximal expiratory flow-volume(MEF25),50％maximal expiratory flow-volume(MEF50),75％maximal expiratory flow-volume(MEF75)of children in the two groups were measured by lung function detector before and 2 weeks after treatment.The adverse reactions of children in the two groups were recorded during treatment.Results The total effective rate of children in the control group and observation group was 82.26％(51/62)and 95.16％(59/62),respectively;the total effective rate of children in the observation group was significantly higher than that in the control group(P＜0.05).There was no significant difference in cough scores during the day and night of children between the two groups before treatment(P＞0.05);the cough scores during the day and night of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the cough scores during the day and night of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in serum HMGB1,TLR4,NF-κB levels of children between the two groups before treatment(P＞0.05);the serum HMGB1,TLR4,NF-κB levels of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the serum levels of HMGB1,TLR4,and NF-κB of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in MEF25,MEF50,and MEF75 of children between the two groups before treatment(P＞0.05);the MEF25,MEF50,and MEF75 of children after treatment were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the MEF25,MEF50,and MEF75 of children in the observation group were significantly higher than those in the control group(P＜0.05).There was no significant difference in serum IL-4,INF-γ levels and the ratio of INF-γ/IL-4 of children between the two groups before treatment(P＞0.05);the serum IL-4 level of children after treatment were significantly lower than those before treatment,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the serum IL-4 level of children in the observation group was significantly lower than that in the control group,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those in the control group(P＜0.05).All children had good drug tolerance during the treatment period,and no significant adverse drug reactions were observed.Conclusion The combination of Xiaokechuan capsules and procaterol hydrochloride has a significant therapeutic effect for pediatric CVA,and its mechanism of action may be related to the regulation of HMGB1-TLR4-NF-κB signal pathway.
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ObjectiveTo investigate effect of Maxing Shigantang and supplemented Guominjian decoction on symptoms and levels of inflammatory cytokines in induced sputum of children with cough variant asthma （CVA）. MethodA total of 118 CVA children who were treated in our hospital from January 2020 to January 2021 were enrolled and randomized into the control group and the observation group with the random number table method. Control group received routine western medicine and the observation group was treated by routine western medicine， Maxing Shigantang， and supplemented Guominjian decoction. In the one-month follow-up， the scores of cough and accompanying symptoms， levels of inflammatory cytokines ［interleukin-10 （IL-10）， interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， neutrophil， eosinophil］ in induced sputum， pulmonary function parameters ［forced vital capacity （FVC）， forced expiratory volume in one second （FEV1）， FEV1/FVC］， and treatment outcomes were compared between the two groups. Moreover， the frequency of acute asthma attacks during the three-month follow-up was also compared. ResultNo cases dropped out from this study. After treatment， the scores of cough and accompanying symptoms were decreased in both groups （P<0.05） and were lower in observation group than in control group （P<0.05）. After treatment， FVC， FEV1， and FEV1/FVC were raised in both groups and were higher in observation group than in control group （P<0.05）. The increase in the level of IL-10 along with the decrease in levels of IL-5， TNF-α， neutrophil， and eosinophil in induced sputum was found in both groups after treatment （P<0.05）， and observation group had higher level of IL-10 and lower levels of IL-5， TNF-α， neutrophil， and eosinophil than the control group （P<0.05）. The effective rate was 86.44% （51/59） in observation group， which was higher than the 69.49% （41/59） in control group （χ2=4.933， P<0.05）. No serious adverse reaction occurred in either group. The frequency of acute asthma attacks during the three-month follow-up was （1.09±0.18） in observation group， which was lower than the （2.83±049） in the control group （P<0.05）. ConclusionRoutine western medicine combined with Maxing Shigantang and supplemented Guominjian decoction can effectively and safely alleviate the airway inflammatory responses， control the clinical symptoms， improve pulmonary function， and reduce the frequency of acute recurrence in the treatment of CVA children.
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Cough variant asthma(CVA)is a common respiratory disease in clinical practice.The only or main clinical manifestation of CVA is cough.It has similar pathological pathogenesis with asthma,but its pathological changes are sligher than asthma.The research of CVA drugs needs appropriate CVA animal models as the research basis.Based on the characteristics of CVA clinical diseases and syndromes of traditional Chinese and western medicine,combined with the clinical diagnostic criteria of traditional Chinese and western medicine,the CVA animal models are combed and analyzed,in order to provide references for the establishment,evaluation and application of CVA animal models.Chemical induction was used to prepare the commonly used animal models of cough variant asthma,including mice,rats and guinea pigs.The selection of sensitizing agent,adjuvant,activator and cough inducing agent was basically the same in the animal models of cough variant asthma,but there were significant differences in the selection of sensitizing method,sensitizing and stimulating dose,modeling cycle and detection index.Western medicine has clear diagnostic criteria for cough variant asthma,while traditional Chinese medicine can classify cough-variant asthma into different types according to different syndromes.At present,the commonly used animal models of cough variant asthma are highly consistent with the diagnostic criteria of western medicine,but not well consistent with the diagnostic criteria of traditional Chinese medicine,which is insufficient to reflect the symptoms of traditional Chinese medicine.The establishment of CVA animal model combining disease and syndrome,including medical syndromes into the model evaluation criteria,meets the requirements of TCM research on CVA animal model.In model evaluation,behavioral manifestations,HE staining of lung tissue,cell counts in BALF and lung function indicators should be considered in various aspects,and airway excitation test,alveolar lavage fluid eosinophil count,behavioral and other aspects should be distinguished from asthma.
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AIM To explore the clinical effects of San'ao Decoction combined with salbutamol on patients with cough variant asthma.METHODS Eighty patients were randomly assigned into control group(40 cases)for 3-month administration of salbutamol,and observation group(40 cases)for 3-month administration of both San'ao Decoction and mifepristone.The changes in clinical efficacy,TCM syndrome scores,serum MMP-9,VEGF and sex hormones(E2,FSH,PRL)and incidence of adverse reactions were detected.The changes in clinical efficacy,EOS,SIgG4,TIgE,Eotaxin,NKA,LTD4,IL-27,SP,R5-R20,Fres,R5,Zrs,PEF diurnal variation rate,FEF25,PEF,ACT score,PAQLQ score,recurrence rate and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with lower recurrence rate(P<0.05).After the treatment,the two groups displayed decreased EOS,TIgE,Eotaxin,NKA,LTD4,SP,R5-R20,Fres,R5,Zrs and PEF diurnal variation rate(P<0.05),and increased SIgG4,IL-27,FEF25,PEF,ACT score,PAQLQ score(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with cough variant asthma,San'ao Decoction combined with salbutamol can improve EOS,TIgE,Eotaxin,SIgG4 levels and airway resistance indices,lung function indices,regulate neurogenic mediators,alleviate airway inflammation injury,enhance life quality,and reduce recurrence rate.
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Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.
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In recent years, the prevalence and medical visits of chronic cough in children are increasing year by year, among which cough variant asthma is one of the main causes of chronic cough in children.The Global Initiative for Asthma points out that cough variant asthma is a disease in which cough is the main or only symptom and is associated with airway hyperresponsiveness.Cough variant asthma, a disease with repeated or persistent cough as the main clinical manifestation, is a subtype of asthma.Due to the lack of typical wheezing symptom, cough variant asthma is easy to be misdiagnosed or missed, leading to lack of standardized treatment.In addition, frequent coughing has a significant impact on the quality of life of children and their family members.In order to improve clinicians′ understanding of cough variant asthma in children, the advances in epidemiology, pathogenesis, diagnosis and treatment of this disease are explained.
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Objective: To observe and evaluate the clinical efficacy and safety of using pediatric Tuina (Chinese therapeutic massage), Tui-Pushing chest-back manipulation, in treating children with cough variant asthma (CVA).Methods: Seventy-two kids with CVA were divided into two groups using the random number table method, with 36 cases in each group. The control group received the conventional Tuina treatment, and the observation group received additional Tui-Pushing chest-back manipulation. The clinical efficacy and adverse reactions were observed and recorded for the two groups. Results: After three treatment courses, compared with the control group, the observation group showed advantages in the total effective rate, reducing the number and intensity of cough and improving the nature of cough (P<0.05). However, at the one-month follow-up, there were no significant differences between the two groups in these parameters (P>0.05). Regarding the adverse reaction rate, there was no significant between-group difference (P>0.05). Conclusion: It is effective and safe to use pediatric Tuina, Tui-Pushing chest-back manipulation, plus the conventional treatment protocol to treat CVA in children.
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ObjectiveTo explore the effect and mechanism of Sangmei Zhike granule （SMZK） on airway inflammation in rats with cough variant asthma（CVA）. MethodSix-week-old male SD rats were randomly divided into normal group， model group， and SMZK （2.48 g·kg-1） group. The rats in the model group and the SMZK group received intraperitoneal injection of a mixed solution containing 10% ovalbumin （OVA） and aluminium hydroxide on the 1st and 8th days and aerosol inhalation of 1% OVA solution from the 15th day for CVA model induction. The intervention lasted for two weeks from the 15th day. At the end of animal manipulation， the lung function was detected and inflammatory cells in the peripheral blood were counted. The serum interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-10 （IL-10） levels were determined. Hematoxylin-eosin （HE） staining was performed on the lungs. Western blot was used to detect the protein expression of nuclear factor kappa-B （NF-κB） and its inhibitor α（IκBα） in lung tissues. ResultCompared with the normal group， the model group showed reduced forced expiratory volume in the first 0.1 second （FEV0.1），FEV0.1/forced vital capacity （FVC），and forced expiratory flow 50% （FEF50%） （P<0.05， P<0.01）， increased white blood cells and eosinophils （P<0.01）， and up-regulated serum IL-4， IL-5， and IL-10 （P<0.01）. As revealed by HE staining， the model group displayed shed epithelial cells of the bronchus， airway stenosis， hyperplasia and expansion of mucous glands， disarrangement of layer structures， disorderly arranged cells， and extensive infiltration of inflammatory cells. The protein expression of NF-κB p65 was higher （P<0.01） and that of IκBα was lower （P<0.01） in the lung tissues of the model group than that in the normal group. Compared with the model group， the SMZK group showed increased FEV0.1，FEV0.1/FVC，and FEF50% （P<0.05）， decreased white blood cells and eosinophils in the peripheral blood （P<0.01）， and declining serum IL-4， IL-5， IL-10 （P<0.01）. HE staining demonstrated mild bronchial mucosal injury and relieved inflammatory cell infiltration， gland hyperplasia， and epithelial degeneration and necrosis in the SMZK group. The protein expression of NF-κB p65 was decreased （P<0.05） and that of IκBα was increased （P<0.05） in lung tissues of the SMZK group than that in the model group. ConclusionSMZK can improve lung function and inhibit airway inflammation in rats with CVA. The underlying mechanism may be related to the regulation of IκBα/NF-κB protein expression in the lungs.
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The wind, phlegm, and blood stasis are important pathogenic factors of cough variant asthma in children, and they are also the pathological products in the occurrence and development of this disease. They have typical pathogenic characteristics. The main pathogenesis characteristics of cough caused by wind, phlegm and blood stasis are as follows that external wind attacks the lungs and induces internal wind, phlegm and dampness accumulates in the lungs, and the lungs fail to declare and descend, and blood stasis obstructs the collaterals and stagnation of Qi. The wind, phlegm, and blood stasis have their own pathogenic characteristics, and their cough-causing also have their own pathogenic characteristics and clinical characteristics. Based on the characteristics of wind, phlegm, and blood stasis, the application of medicine based on the differentiation of symptoms and signs can effectively prevent and treat this disease, and provide theoretical basis and treatment ideas for the treatment of cough variant asthma in children with Chinese medicine.
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Objective:To observe the clinical efficacy of Erchentang combined with Sanzi Yangqintang in the treatment of cough variant asthma （CVA） in children with phlegm-evil accumulation lung syndrome and its influence on airway inflammation and airway hyperresponsiveness （AHR）. Method:A total of one hundred and sixteen children were randomly divided into observation group and control group 58 cases in each group. Patients in both groups took montelukast sodium chewable tablets orally， 5 mg/time， once daily， at night before bedtime. In observation group， patients took Erchentang and Sanzi Yangqintang modified granules orally. While patients in control group took Erchentang and Sanzi Yangqintang placebo granules orally. Treatment course continued six weeks for two groups. Before and after treatment， the cough symptom scores and phlegm evil accumulating lung syndrome scores were recorded every week. The cough remission time and cough disappearance time were recorded， followed up for 24 weeks to record cough recurrence. Leicester Cough quality of life questionnaire （LCQ） was scored before and after treatment. The ratio of induced sputum eosinophils （EOS） and the levels of interleukin-4 （IL-4）， IL-5， IL-12， IL-13 were measured before and after treatment. The cumulative doses of exhaled nitric oxide （FeNO） and methacholine （PD20） were measued before and after therapy. Safety evaluation was conducted. Result:The scores of cough symptom and phlegm-evil accumulation lung syndrome at different time points were decreased gradually in two groups of children after treatment （<italic>F</italic><sub>control group</sub>=5.277， <italic>F</italic><sub>observation group</sub>=7.636，<italic>P</italic><0.01）. The scores of cough symptom and phlegm-evil accumulation in the lung syndrome of observation group were lower than those in control group （<italic>P</italic><0.01） at the same period. The durations of cough relief and cough disappearance in observation group were shorter than those in control group （<italic>P</italic><0.01）. Within 24 weeks of follow-up， the recurrence rate of children in observation group was 68.97% （40/58）， lower than 84.48% （49/58） in control group （<italic>χ</italic><sup>2</sup>=3.917，<italic>P</italic><0.05）. Children in observation group had fewer relapses than those in control group （<italic>P</italic><0.01）. The total LCQ scores and scores of all dimensions in observation group were higher than those in control group （<italic>P</italic><0.01）. The EOS， IL-4， IL-5 and IL-13 levels in observation group were lower than the data in control group， and IL-12 level was higher than that in control group （<italic>P</italic><0.01）. FeNO of children in observation group was lower than that in control group （<italic>P</italic><0.01）， while PD20 was more than that of control group （<italic>P</italic><0.01）. The total effective rate of clinical curative effect of children in observation group was 96.55% （56/58）， which was higher than 82.76% （48/58） in control group （<italic>χ</italic><sup>2</sup>=5.948，<italic>P</italic><0.05）. Conclusion:Erchentang combined with Sanzi Yangqintang for children with CVA phlegm evil accumulation lung syndrome can further control the symptoms of cough， shorten the course of cough， improve the quality of life， and reduce airway inflammation and AHR， reduce the recurrence rate. The clinical efficacy is better than using montelukast only， and it is safe and has good clinical value.
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OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.
Subject(s)
Child , Humans , Asthma , Core Binding Factor Alpha 3 Subunit/genetics , Cough , Interleukin-13 , MicroRNAs/genetics , Th1 Cells , Th1-Th2 Balance , Th2 CellsABSTRACT
Objective:To explore the effect of modified Xiongxiesan on the proliferation of airway smooth muscle tissues and the expressions of matrix metalloproteinase-9（MMP-9）， tissue inhibitor of metalloproteinase-1 （TIMP-1） in cough variant asthma （CVA） model rats. Method:A total 48 male SD rats were randomly divided into the normal control group （8 rats） and model group （40 rats）. CVA model of rats were established through the intraperitoneal administration with 2 mg ovalbumin （OVA） and 100 mg Al（OH）3， and then aerosol inhalation of 1％ OVA 15 days later. The same volume of sterile saline was given to the normal group through the intraperitoneal injection. Then 40 rats in the modeling group were randomly divided into model group， modified Xiongxiesan group （TCM group， 6 g·kg-1·d-1）， montelukast group （0.4 mg·kg-1·d-1）， chemokine receptor1/2 （CXCR1/2） inhibitor group （G31P group injected subcutaneously via the neck with a dose of 0.5 mg·kg-1 every other day）， and CXCR1/2 inhibitor and modified Xiongxiesan group （G31P+TCM group）， with 8 rats in each group. The control group and the model group were orally given distilled water 10 mL·kg-1·d-1. Then the rats were sacrificed， and lung samples were collected. Histological changes were examined by hematoxylin-eosin（HE）. Basement membrane perimeter （PBM），wall area of bronchial tube （WAt），wall area of bronchial smooth muscle （WAm） and the number of smooth muscle cells （N） were measured using image pro-plus software and standardized based on PBM. The expressions of PCNA， MMP9 and TIMP1 were detected by immunohistochemistry. Result:Compared with the control group， there were a large number of inflammatory cells infiltration and moderate hyperplasia of smooth muscle area in the model group， which however were alleviated in other groups. The expressions of PCNA and MMP-9，TIMP1 were higher in the model group，which were reduced in other groups significantly. Conclusion:Modified Xiongxiesan can reduce the thickness of airway smooth muscle tissue in the CVA model rats， which may be correlated with the inhibition of the CXCR1/2 pathway， thereby reducing the proliferative activity of smooth muscle tissue and inhibiting the expression of related matrix metalloproteinases.
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Cough-variant asthma is the most common cause of chronic cough. It may progress to classic asthma and therefore requires adequate treatment intervention. We experienced two cases of cough-variant asthma that was refractory to standard drug therapy but improved after additional administration of kumibinroto. In Case 1, the patient was a 46-year-old woman receiving hormone therapy after breast cancer surgery. She developed cough-variant asthma 5 years ago, and though she has received drug therapy, the symptoms aggravated. Cough continued to appear at night without improvement of asthma symptoms. However, the symptoms improved with subsequent administration of kumibinroto. In Case 2, the patient was a 47-year-old woman who developed cough-variant asthma after childbirth, which repeatedly worsened and improved. The cough-variant asthma aggravated after change of workplace and did not improve with drug therapy. However, asthma symptoms improved with oral administration of kumibinroto and hangekobokuto, and subsequent administration of kumibinroto alone. In both patients, the asthma was seasonal. These cases suggest that kumibinroto administration may contribute to the improvement of cough-variant asthma.
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OBJECTIVES@#Cough variant asthma (CVA) is the main cause of obstinate cough. This study aimed to observe the therapeutic effect of Xiaochuan pill on CVA in a rat model, and to explore the mechanisms.@*METHODS@#The rats were sensitized and challenged with 4% ovaibumin (OA) and 2% Al(OH) to establish the CVA models. They were treated with Xiaochuan pill (at the dose of 0.9, 1.8, 3.6 g/kg) or montelukast sodium once a day for 14 days. After 7 and 14 days of intervention, 5 and 10 rats were randomly selected from each group to collect bronchoalveolar lavage fluid (BALF), trachea, and lungs. The number of white blood cells (WBC) and eosinophils (EOS), and the levels of IL-1β, TNF- α, and IFN-γ in BALF were detected. Histopathological examination of lung tissue was performed to observe the histomorphological changes. The expressions of TLR4, MyD88, NF-κBp65, and p-p65 in lung tissue were detected by Western blotting.@*RESULTS@#The numbers of WBC and EOS in BALF of CVA rats were significantly decreased by Xiaochuan pill (<0.05 or <0.01). The hyperplasia of tracheal, bronchial mucosa and the infiltration of inflammatory cells in lung were alleviated obviously. After 14 d of intervention, high dose of Xiaochuan pill significantly increased the level of IFN- γ (<0.01), reduced the levels of IL-1β (<0.05) and TNF-α (<0.05), and decreased the expressions of TLR4, MyD88, p65, and p-p65 (<0.05 or <0.01).@*CONCLUSIONS@#Xiaochuan pill exerts the significant therapeutic effect on obstinate cough in rats. The mechanism of action may be related to the regulation of TLR4-MyD88-NF-κBp65 signaling pathway as well as the inflammation and immune response.
Subject(s)
Animals , Rats , Cough , Myeloid Differentiation Factor 88 , NF-kappa B , Signal Transduction , Toll-Like Receptor 4 , Tumor Necrosis Factor-alphaABSTRACT
Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.
Subject(s)
Quinolines/therapeutic use , Asthma/drug therapy , Anti-Asthmatic Agents/therapeutic use , Protective Agents/therapeutic use , Cough/drug therapy , RNA, Long Noncoding/metabolism , Acetates/therapeutic use , Asthma/blood , Cough/blood , Disease Models, Animal , Mice, Inbred BALB CABSTRACT
OBJECTIVES: To evaluate the quantitative changes and diagnostic performance of volumetric capnography (VCap) parameters in patients with cough variant asthma. METHODS: This cross-sectional study enrolled 31 patients with cough variant asthma and 30 patients with chronic cough without asthma between November 2010 and March 2012. VCap measurements were recorded at baseline, during the five steps of the histamine challenge, and after bronchodilation with salbutamol. They were then compared between the baseline and histamine challenge, and between the two groups. Receiver operating characteristic curve analysis was performed for different VCap measurements. RESULTS: The slope of phase III (dc/dv3) and the ratio of phase III slope to phase II slope (SR23%) decreased from baseline upon challenge with 1.1 mg histamine in cough variant asthma patients but increased in patients with chronic cough without asthma. Additionally, the change upon challenge with 1.1 mg histamine in dc/dv3 from baseline (S6-S1dc/dv3) in cough variant asthma patients had the largest area under the curve (AUC) (0.814, 95% CI: 0.697-0.931; p<0.001). The AUC for change upon challenge with 1.1 mg histamine in SR23% from baseline was 0.755 (95%CI: 0.632-0.878; p<0.001). At a cutoff of 19.8, S6-S1 dc/dv3 had a sensitivity of 74.2% and specificity of 90.0% and at a cutoff of 40.7, S6-S1 SR23% had a sensitivity of 48.4% and specificity of 96.7%. CONCLUSION: Patients with cough variant asthma exhibit distinct VCap responses for dead space parameters upon challenge with histamine in comparison to patients with chronic cough. VCap parameters like phase III slope and phase III/phase II slope ratio could be used to aid the diagnosis of cough variant asthma.