Is there a correlation between the changes in airway inflammation and the changes in respiratory mechanics after vaping in patients with asthma?

BACKGROUND Electronic cigarettes(ECs)have been promoted as alternatives to traditional cigarettes.To investigate ECs’effects on respiratory system,especially in patients with respiratory diseases.METHODS We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers.All were subjucted to pulmonary function tests(PFTs),impulse oscillometry(IOS),fraction exhaled Nitric Oxide(FeNO),exhaled breathe condensate(EBC)and biomarker measurements before and after vaping one nicotinecontaining EC.RESULTS The increase in FeNO 30 minutes after EC,reflecting airway inflammation,significantly correlated with increase of residual volume(RV),total lung capacity,respiratory impedance at 5 Hz(Z5Hz)and respiratory resistance at 5 and 20 Hz(R5Hz and R20Hz).No significant correlations were found between EBC biomarkers'changes and respiratory mechanics.CONCLUSION This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.

Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats

Objective： To investigate the influence of Danshen Injection on airway inflammation and CD4^＋CD25^＋ regulatory T cells（CD4^＋CD25^＋ Tr） of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods： 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids （BALF） were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain （HE）. Flow cytometry was used to detect the CD4^＋CD25^＋ Tr ratio in peripheral blood mononuclear cells （PBMCs）. Results： Total cell, the percentage of lymphocytes, neutrophils and eosinophils （Eos） in BALF of Danshen Injection-treated group were lower than that in asthma group （P〈0.05, P〈0.01）. Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4^＋CD25^＋ Tr of asthma group was lower than that of control and Danshen Injection treated group （P〈0.05）. Conclusion： Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4^＋CD25^＋ Tr.

Effect of All-trans Retinoic Acid on Airway Inflammation in Asthmatic Rats and Its Mechanism

Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB, intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-κB activation and expression.

Effects of Medication Use on Small Airway Function and Airway Inflammation in Patients with Clinically Controlled Asthma

Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.

Effects of <i>Baicalin</i>and <i>Ligustrazine</i>on airway inflammation and remodeling and underlying mechanism in asthmatic rats

Aim: To explore the effects of Baicalin and Ligustrazine on airway inflammation and construction and underlying mechanisms through the expressions of GATA-3, IL-5, MMP-9 and TIMP-1 in asthmatic rats. Methods: 30 Wistar rats were randomly divided equally into five groups. Lung tissues were sliced. WBC and Eos in lung tissue were estimated by HE stain and the expressions of IL-5, GATA-3, MMP-9, TIMP-1 and collagen type IV in lung tissue were observed by immunohistochemistry. The airway wall and airway smooth muscle thicknesses were measured by computed image analysis system. Results: Compared with asthma group, EOS counts and the expression of IL-5 and GATA-3 in the lung tissue were significantly lower in normal controlled groups (P Baicalin or Ligustrazine, EOS decreased, and the thicknesses of airway wall and airway smooth muscle became thinner compared with asthma group. Meanwhile, the expression of collagen type IV, IL-5, GATA-3, MMP-9 and TIMP-1 significantly decreased (P < 0.05). Airway wall thickness and collagen type Ⅳ were associated with Eos, IL-5, TAGA-3, MMP-9, TIMP-1 and MMP-9/ TIMP-1. Conclusion: Two herbs could diminish infiltration of EOS with inhibiting the expressions of IL-5, and GATA-3, meanwhile, decrease the deposition of collagen type IV and the thickness of the airway smooth muscle through regulating MMP-9, TIMP-1 level and the balance between MMP-9 and TIMP-1, additionally, had synergetic effects.

The influence of vitamin D3 on airway inflammation and osteopontin expression in cough variant asthma rats

Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.

Experimental study on the regulation effect of Qiaoqin Qingfei agent on cough variant asthma based on airway neurogenic inflammation

Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.

Effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma

Objective:To study the effect of anxiety and depression on pulmonary function as well as airway inflammation and remodeling in patients with bronchial asthma.Methods: A total of 118 adult patients with bronchial asthma who were treated in our hospital between September 2015 and January 2017 were divided into pure depression group (n=30), pure anxiety group (n=47), depression + anxiety group (n=19) and mental health group (n=22) according to the Self-Rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) score. The differences in the levels of pulmonary function parameters as well as the contents of serum inflammatory factors and airway remodeling indexes were compared among the four groups. Results: FEV1, PEF and FVC levels as well as serum TIMP-1 contents of pure depression group, pure anxiety group and depression + anxiety group were lower than those of mental health group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of mental health group, and FEV1, PEF and FVC levels as well as serum TIMP-1 content of depression + anxiety group were lower than those of pure depression group and pure anxiety group while serum IL-2, IL-4, IL-8, IL-33, VEGF, OPN, TGF-β1 and MMP-9 contents were higher than those of pure depression group and pure anxiety group. Conclusion: Anxiety and depression can aggravate the pulmonary function injury, increase airway inflammation and promote airway remodeling process in patients with bronchial asthma.

Effect of pediatric asthma complicated by respiratory virus infection on airway remodeling and inflammation

Objective:To study the effect of pediatric asthma complicated by respiratory virus infection on airway remodeling and inflammation.Methods:A total of 41 children with asthma complicated by respiratory virus infection who were treated in our hospital between May 2012 and March 2016 were collected as observation group, and 50 children with asthma alone who were treated in our hospital during the same period were selected as control group. High-resolution CT was used to determine the right upper lobe apical segment (RB1) and the left lower lobe posterior basal segment (LB10) airway remodeling parameters of two groups of patients, and serum airway remodeling index and inflammatory factor contents were detected. Results: LA, WA and TA levels of RB1 and LB10 of observation group were significantly lower than those of control group, serum airway remodeling indexes TGF-β1, Smad3, PⅠNP and PⅢNP contents were higher than those of control group, serum inflammation indexes IL-4, IL-5 and TNF-α contents were higher than those of control group.Conclusion:Complication of respiratory virus infection can aggravate the airway remodeling and systemic inflammation in children with asthma.

Effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma

Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 patients with cough variant asthma who were treated in our hospital between January 2014 and May 2016 were collected and divided into the control group (n=30) who received conventional inhalant treatment and the observation group (n=30) who received inhalant combined with Dingchuan Zhike decoction treatment according to single-blind randomized controlled method, and the treatment lasted for 6 months. Before treatment and after 6 months of treatment, high-resolution CT was used to determine the airway remodeling index levels, RIA method was used to detect the peripheral blood airway remodeling index contents, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of inflammatory mediators in induced sputum and the PARC/CCL-18 in serum.Results: Before treatment, the differences in the airway remodeling degree as well as the contents of inflammatory mediators and PARC/CCL-18 were not statistically significant between the two groups. After 6 months of treatment, CT airway remodeling indexes LA and TA levels of observation group were higher than those of control group while WA level was lower than that of control group, and peripheral blood airway remodeling indexes CTGF, YKL-39, MMP-9 and TIMP-1 contents were lower tha=n those of control group;inflammatory mediators IL-5, IL-6 and IL-8 contents in induced sputum of observation group were lower than those of control group, and serum PARC/CCL-18 content was lower than that of control group.Conclusion:Inhalant combined with Dingchuan Zhike decoction can inhibit the airway remodeling and reduce the airway inflammation in patients with cough variant asthma.

FGF2 is overexpressed in asthma and promotes airway in airway epithelial cells

Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulating the Phosphoinositide 3-kinase/Akt Pathway in Rat Pups

Objective To evaluate the effect of diisononyl phthalate（DINP） exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages（0, 5, 50, and 500 mg/kg of body weight per day）. The pups were sensitized and challenged by ovalbumin（OVA）. The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin（HE） staining; and the relative cytokines in phosphoinositide 3-kinase（PI3K）/Akt pathway were measured by enzyme-linked immunosorbent assay（ELISA） and western blot analysis. Results There was no significant difference in DINP＇s effect on airway hyperresponsiveness（AHR） between male pups and female pups. In the 50 mg/（kg·d） DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance（RI） compared with those from controls（P〈0.05）. Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/（kg·d） DINP-treated group. However, in the 5 and 500 mg/（kg·d） DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Objective:To evaluate the inflammatory pattern and the interferon(IFN)-γin the bronchial secretion of asthma patients in response to acute cold bronchoprovocation.Material and methods:We enrolled 42 patients with asthma.We assessed asthma by Asthma Control Test,the lung function by spirometry before and after the bronchodilator test,followed by collecting induced sputum.The next day,we collected exhaled breath condensate(EBC)and conducted a 3-minute isocapnic hyperventilation with cold air(IHCA),followed by collecting spontaneously produced sputum.Results:Group 1 included 20 patients with cold airway hyperresponsiveness(CAHR),and group 2 included 22 patients without CAHR.In both groups,a high level of neutrophils in bronchial secretion was observed before and after IHCA.In response to IHCA,the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1.The baseline epitheliocytes and the concentration of IFN-γafter IHCA had an inverse relationship(r=-0.60;P=0.017).The baseline IFN-γin EBC before and after IHCA was lower in group 1.Airway response to cold exposure directly correlated with IFN-γlevels after IHCA(Rs=0.42;P=0.014).Conclusion:In asthma patients with CAHR,there is a relationship between the persistence of mixed inflammation and the level of IFN-γin the bronchi.IFN-γin response to IHCA is decreased with increased cytokine utilization during cold bronchospasm,which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells(Th)1 immune response.

Anti-asthmatic mechanism of the Huashanshen dripping pill via suppressing contraction of the airway smooth muscle

Background:The Huashanshen(HSS)dripping pill has been widely used in asthma for a long time in China.However,the relaxant mechanism of HSS is not well understood.Methods:In this report,high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify the constituents in rat plasma after oral administration of HSS.Ovalbumin-sensitized allergic asthma and isolated trachea were studied for the anti-asthmatic mechanism of HSS.Results:D-anisodamine,L-anisodamine,scopolamine and atropine were detected in the rat plasma containing HSS.It was clear that the HSS inhibited the release of inflammatory mediators,regulated the balance of T-helper 1 and T-helper 2 to reduce the airway inflammation,and relaxed the tracheal smooth muscle by controlling the KCa channel,Ca^(2+)influx and release to reduce the airway hyperresponsiveness.Conclusion:Atropine,anisodamine and scopolamine might be active compounds of HSS which inhibited the release of inflammatory mediators,regulated the balance of Th1/Th2,and relaxed the tracheal smooth muscle to reduce airway hyperresponsiveness.

IgE regulates airway smooth muscle phenotype:Future perspectives in allergic asthma

The purpose of this commentary is to highlight the emerging role of IgE on airway smooth muscle(ASM) cells function through activation of the high-affinity Fc receptor for IgE. We discuss the potential implications of IgE-mediated ASM sensitization in airway inflammation and remodeling, the hallmark features of allergic asthma.

Bronchoalveolar Lavage and Histologic Characterization of Inhaled Heparin in Asthmatic Guinea Pigs

Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.

FeNO及血清β-catenin水平与支气管哮喘患儿气道炎症因子、肺功能相关指标的相关性分析

目的探讨呼出气一氧化氮(FeNO)、血清β-连环素(β-catenin)水平与支气管哮喘(BA)患儿气道炎症因子、肺功能指标水平的相关性。方法选取2022年1月至2023年1月该院收治的120例BA患儿作为研究对象,其中急性发作期组78例,缓解期组42例;另外选取同时期在该院体检的118例健康儿童作为对照组。检测3组研究对象的气道炎症因子[高敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、转化生长因子-β(TGF-β)、免疫球蛋白E(IgE)、外周血嗜酸性粒细胞计数(EOS)]及肺功能指标[用力呼气容积肺活量(FVC)、第1秒用力呼气量(FEV1)、FEV1/FCV百分比(FEV1%)、最高呼吸气流(PEF)];采用酶联免疫吸附试验检测各组血清β-catenin和FeNO水平;采用Pearson相关分析FeNO、β-catenin水平与肺功能相关指标、气道炎症因子水平的相关性;绘制受试者工作特征(ROC)曲线评估FeNO、血清β-catenin对BA患儿急性发作的诊断价值。结果与对照组相比,缓解期组与急性发作期组FeNO水平、EOS及血清hs-CRP、IL-17、IL-6、TGF-β、IgE、β-catenin水平明显升高(P<0.05),FVC、FEV1、FEV1%、PEF明显降低(P<0.05);与缓解期组相比,急性发作期组FeNO水平、EOS及血清hs-CRP、IL-17、IL-6、TGF-β、IgE、β-catenin水平明显升高(P<0.05),FVC、FEV1、FEV1%、PEF明显降低(P<0.05);Pearson相关性分析结果显示,急性发作期BA患儿FeNO及血清β-catenin水平均与hs-CRP、IL-17、IL-6、TGF-β、IgE水平及EOS呈正相关(P<0.05),与FVC、FEV1、FEV1%、PEF呈负相关(P<0.05);ROC曲线分析结果显示,FeNO、血清β-catenin水平单独及联合诊断急性发作期BA患儿的AUC分别为0.849、0.878、0.935,二者联合诊断的AUC显著高于FeNO、血清β-catenin单独诊断(Z=2.845,P=0.002;Z=1.885,P=0.030)。结论BA患儿FeNO及血清β-catenin水平与气道炎症因子hs-CRP、IL-17、IL-6、TGF-β、IgE水平及EOS呈正相关,与肺功能相关指标FVC、FEV1、FEV1%、PEF呈负相关,二者对于急性发作期BA的诊断具有重要价值,可用于BA患儿的病情评估。

Inhibitory Effect of Dexamethasone on Expression of Cysteine-rich 61 Protein in Airway Epithelial Cells of Allergic Mouse Models

Summary： In order to study whether cysteine-rich 61 protein （cyr61） is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone （Dxm） on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group （n=15）, control group （n=10） and Dxm group （n=15）. The asthma group was sensitized and challenged by ovalbumin （OVA）. The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immuno- histochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid （BALF） by using en- zyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in BALF was also ana- lyzed. The results showed that the cyr61 expression was highest in asthma group （P〈0.05）, followed by Dxm group （P〈0.05） and control group. The cyr61 had a positive correlation with the total nucleated cells （r=0.867, P〈0.05）, especially eosinophils （r=0.856, P〈0.05）, and eotaxin level （r=0.983, P〈0.05） in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.

穗花杉双黄酮调节cGAS-STING信号通路对哮喘幼年大鼠气道炎症的影响

目的探讨穗花杉双黄酮(AF)对哮喘幼年大鼠气道炎症的影响并初步探讨其机制。方法采用腹腔注射联合雾化吸入卵白蛋白(OVA)法诱导幼年SD大鼠建立哮喘模型,将大鼠随机分为哮喘模型(M)组、地塞米松(DXMS)组、AF低(AF L)、中(AF M)、高(AF H)剂量组和正常对照(CT)组。给药结束后,无创肺功能仪检测气道反应性,通过吉姆萨(Giemsa)染色分析支气管肺泡灌洗液(BALF)中炎性细胞类型并计数,使用苏木素-伊红(HE)染色评价肺组织和支气管组织病理特征,酶联免疫吸附剂实验(ELISA)检测血清炎症因子的含量,Western blot检测肺组织GMP-AMP合酶(cGAS)、干扰素基因刺激物(STING)、磷酸化-干扰素调节因子3(p-IRF3)和干扰素调节因子3(IRF3)蛋白表达。结果与CT组相比,M组幼年大鼠肺组织和支气管组织可见明显病理损伤,气道反应性、肺组织、支气管组织病理评分、BALF中炎性细胞总数及单核细胞、嗜酸性粒细胞、中性粒细胞和淋巴细胞的数量显著增加、血清炎症因子以及肺组织c GAS、STING、p-IRF3/IRF3蛋白表达显著增加(P<0.05);与M组相比,DXMS和高剂量AF治疗哮喘大鼠后肺、支气管组织病理损伤缓解,气道反应性、肺组织、支气管组织病理评分、BALF中炎性细胞总数显著降低、血清炎症因子以及肺组织c GAS、STING、p-IRF3/IRF3蛋白表达明显降低(P<0.05)。结论AF可缓解哮喘幼年大鼠的气道炎症,其可能是通过抑制cGAS-STING信号通路实现的。

Role of hydrogen sulphide in airways

The toxicity of hydrogen sulfide(H2S) has been known for a long time, as it is prevalent in the atmosphere. However accumulative data suggest that H2 S is also endogenously produced in mammals, including man, and is the third important gas signaling molecule, besides nitric oxide and carbon monoxide. H2 S can be produced via non enzymatic pathways, but is mainly synthesizedfrom L-cysteine by the enzymes cystathionine-γ-lyase, cystathionine-β-synthetase, cysteine amino transferase and 3-mercaptopyruvate sulfurtransferase(3MTS). The formation of H2 S from D-cysteine via the enzyme D-amino acid oxidase and 3MTS has also been described. Endogenous H2 S not only participates in the regulation of physiological functions of the respiratory system, but also seems to contribute to the pathophysiology of airway diseases such as chronic obstructive pulmonary disease, asthma and pulmonary fibrosis, as well as in inflammation, suggesting its possible use as a biomarker for these diseases. This review summarizes the different implications of hydrogen sulfide in the physiology of airways and the pathophysiology of airway diseases.