Effects of Qingfei Shenshi Decoction on the expressions of MMP-2, MMP-9 and TIMP-1 in lung tissue of bronchial asthma mice / 国际中医中药杂志

Objective:To investigate the effects of Qingfei Shenshi Decoction on the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue inhibitor of metalloproteinase timps-1 (TIMP-1) in lung tissue of asthma mice.Methods:Totally 50 male BALB/C mice were divided into 5 groups: normal group, model group, dexamethasone group, Qingfei Shenshi Decoction low- and high-dosage groups (10 mice /group) according to random number table method. Asthma model mice were prepared by ovalbumin (OVA) challenge method. After successful modeling, the dexamethasone group was given dexamethasone for gavage at the rate of 1.56 mg/kg, while Qingfei Shenshi Decoction groups were given high and low doses of Qingfei Shenshi Decoction for gavage at the rate of 14.235 g/kg and 28.470 g/kg, respectively. Normal group and model group were given 0.9% sodium chloride solution by gavage. At the end of gavage administration for 4 weeks, the airway reactivity (Penh value) in each group was detected; HE staining was used to observe the pathological changes of lung tissue; the contents of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor -α (TNF-α) in alveolar lavage fluid were determined by enzyme Linked immunosorbent assay (ELISA); the expressions of MMP-2, MMP-9 and TIMP-1 in lung tissue were detected by Western-blot.Results:Compared with model group, the damage of airway wall and alveolar wall of lung tissue in Qingfei Shenshi Decoction groups was significantly reduced. Compared with model group, the Penh value, IL-6, IL-1β and TNF-α levels in Qingfei Shenshi Decoction low- and high-dosage groups decreased ( P<0.05), and the expressions of MMP-9, MMP-2 and TIMP-1 in lung tissue decreased ( P<0.05), with a certain dose dependence. Conclusion:Qingfei Shenshi Decoction can effectively alleviate airway inflammation, reduce airway hyperresponsiveness, improve lung function and inhibit airway remodeling in asthmatic mice. Its mechanism may be related to down-regulating the expressions of MMP-2, MMP-9 and TIMP-1.

Effects of blistering cupping combined with thunder-fire moxibustion on the efficacy and airway remodeling of cold-wheezing syndrome in bronchial asthma / 中国针灸

OBJECTIVE@#To investigate the clinical efficacy of the combined application of blistering cupping with thunder-fire moxibustion in treating bronchial asthma of cold-wheezing syndrome, and its influences on airway remodeling, inflammatory factors, lung function, and quality of life on the base of conventional western medicine treatment.@*METHODS@#A total of 76 patients with bronchial asthma of cold-wheezing syndrome were randomly divided into an observation group and a control group, 38 cases in each group. In the control group, the basic treatment was used, i.e. budesonide formoterol powder inhalation. In the observation group, on the basis of the treatment as the control group, blistering cupping combined with thunder-fire moxibustion was supplemented, Dazhui (GV 14), Danzhong (CV 17) and bilateral Feishu (BL 13), Gaohuang (BL 43), and Zhongfu (LU 1) were selected; blistering cupping was administered once a day and thunder-fire moxibustion was given twice a day. One course of treatment was composed of 7 days in both groups, and 2 courses of treatment were required. Before and after treatment, the airway remodeling indexes (matrix metalloproteinase-9 [MMP-9], tissue inhibitor of matrix metalloproteinase-1 [TIMP-1], and transforming growth factor-β1 [TGF-β1]) and inflammatory indexes (interleukin [IL] -1β、IL-25) were detected by using radioimmunoassay in the patients of the two groups. The lung function, traditional Chinese medicine symptom score, and asthma quality of life questionnaire (AQLQ) score were observed in the patients of the two groups.@*RESULTS@#After treatment, the serum levels of MMP-9, TIMP-1, TGF-β1, IL-1β, IL-25, peak expiratory flow (PEFR), traditional Chinese medicine symptom scores, and AQLQ scores were decreased compared with those before treatment in the patients of the two groups (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). After treatment, the first second forced expiratory volume (FEV1) and peak expiratory flow rate (PEF) were increased compared with those before treatment in the two groups (P<0.05), and the results in the observation group were higher than those in the control group (P<0.05).@*CONCLUSION@#On the basis of the conventional western medicine treatment, the combination of blistering cupping with thunder-fire moxibustion can effectively ameliorate the clinical symptoms of patients, reduce inflammatory levels, inhibit airway remodeling and improve the lung function and quality of life in the patients with bronchial asthma.

Effect mechanism of acupuncture for anti-asthmatic airway remodeling based on TGF-β1 / Smad3 signaling pathway / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6) + "Yuji" (LU 10) for the airway remodeling in asthma rats based on the transforming growth factor-β1 (TGF-β1)/ Smad family member 3 (Smad3) signaling pathway; and explore the efficacy difference between the two acupoint combinations.@*METHODS@#Forty SPF male SD rats, aged 4 weeks, were randomly divided into a blank group (n = 10) and a modeling group (n = 30). The ovalbumin (OVA) sensitization method was used to establish asthma model in the modeling group. After successful model preparation, the rats of the modeling group were randomized into a model group, an acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) (AAF) group, and acupuncture at "Kongzui" (LU 6)+"Yuji" (LU 10) (AAK) group, with 10 rats in each one. Starting from day 15 of the experiment, 5 min after motivating, acupuncture was applied to "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6)+"Yuji" (LU 10) in the AAF group and the AAK group respectively. The intervention was delivered for 30 min each time, once daily, lasting 3 weeks consecutively. Using lung function detector, the airway resistance (RL) and dynamic compliance (Cdyn) of the lungs were detected. The histomorphology of lung tissues was detected with HE staining and Masson staining, and the mRNA and protein expression of TGF-β1 and Smad3 in lung tissues was detected with the real-time PCR and Western blot methods.@*RESULTS@#Compared with the blank group, RL was increased and Cdyn was decreased in the rats of the model group (P<0.01); and RL was reduced and Cdyn was increased in the AAF group and the AAK group when compared with those in the model group (P<0.01, P<0.05). The rats of the model group had bronchial lumen stenosis, inflammatory cell infiltration, collagen fibre hyperplasia and thickened smooth muscle in the lung tissues when compared with those in the blank group; and in comparison with the model group, all of the above morphological changes were attenuated in the AAF group and the AAK group. Besides, these morphological changes of the lung tissues were more alleviated in the AAF group when compared with those in the AAK group. In comparison with the blank group, the mRNA and protein expression of TGF-β1 and Smad3 of the lung tissues was increased in the model group (P<0.01), and it was reduced in the AAF group and the AAK group when compared with that in the model group (P<0.05, P<0.01). The mRNA expression of TGF-β1 and Smad3 was lower in the AAF group when compared with that in the AAK group (P<0.05).@*CONCLUSION@#Acupuncture at either "Feishu" (BL 13)+"Dingchuan" (EX-B 1) or "Kongzui" (LU 6)+"Yuji" (LU 10) reduces the airway remodeling in the rats with asthma, which may be related to the down-regulation of mRNA and protein expression of TGF-β1 and Smad3. The better efficacy is obtained with acupuncture at "Feishu" (BL 13)+"Dingchuan" (EX-B 1).

Research progress on effect and mechanism of diesel exhaust particles on asthma / 环境与职业医学

As a source of traffic-related air pollution, diesel particulate matter (DPM) associate with a variety of lung-related diseases, but there is no systematic review of the relationship between DPM and the development and progression of asthma. This article reviewed the relationship between DPM and asthma, the effect and mechanism of DPM on airway inflammation and remodeling in asthma, and illustrated that DPM exposure may participate in airway inflammation and remodeling through oxidative stress, immune regulation and regulation of lung and intestinal microecology, so as to promote the development and progression of asthma.

Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway / 中国中药杂志

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

Effects of nebulization with high-dose budesonide combined with ipratropium bromide on airway remodeling and mucus secretion in patients with AECOPD / 中国基层医药

Objective:To investigate the effects of nebulization with high-dose budesonide (BUD) combined with ipratropium bromide (IB) on airway remodeling and mucus secretion in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Methods:Ninety patients with AECOPD who received treatment in Wenling Hospital of Traditional Chinese Medicine between January 2020 and June 2021 were included in this study. They were assigned to the conventional-dose group ( n = 45, odd number) and high-dose group ( n = 45, even number) according to the number of admission. In the conventional-dose group, nebulization with IB (0.5 mg administered within 20 minutes, three times daily) and BUD (2 mg administered within 20 minutes, twice daily) was performed. In the high-dose group, nebulization with IB (0.5 mg administered within 20 minutes, three times daily) and BUD (4 mg administered within 20 minutes, twice daily) was performed. After nebulization, a mouthwash was required in each group. After 7 days of treatment, clinical efficacy was compared between the two groups. Before and 7 days after treatment, airway remodeling level (matrix metalloproteinase-9 and interleukin-8), airway mucus secretion (mucin-5ac and neutrophil elastase) and the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the high-dose group was significantly higher than that in the conventional-dose group [95.56% (43/45) vs. 82.22% (37/45), χ2 = 4.05, P < 0.05]. After 7 days of treatment, serum matrix metalloproteinase-9 and interleukin-8 levels in the high-dose group were (416.96 ± 30.96) μg/L and (6.33 ± 1.03) μg/L, respectively, which were significantly lower than those in the conventional-dose group [(452.25 ± 32.16) μg/L, (7.85 ± 1.24) μg/L, t = 5.30, 6.32, both P < 0.001)]. After 7 days of treatment, serum mucin-5ac and neutrophil elastase levels in the high-dose group were (1.33 ± 0.21) μg/L and (4.06 ± 1.03) μg/L, respectively, which were significantly lower than those in the conventional-dose group [(1.58 ± 0.23) μg/L, (5.11 ± 1.14) μg/L, t = 5.38, 4.58, both P < 0.001]. There was no significant difference in incidence of adverse reactions between high-dose and conventional-dose groups [8.89% (4/45) vs. 4.44% (2/45), χ2 = 0.71, P > 0.05). Conclusion:Nebulization with high-dose BUD combined with IB for treatment of AECOPD can improve airway remodeling, reduce airway mucus hypersecretion and has definite therapeutic effects. Findings from this study are of great innovation and science.

Molecular mechanism of airway epithelial cells involved in airway remodeling through epithelial mesenchymal transition in asthma / 国际儿科学杂志

Airway remodeling is one of the main pathological features of bronchial asthma.Airway remodeling may lead to increased airway hyperresponsiveness and pulmonary function decline in asthmatic patients.Some studies suggest that airway epithelial cells may play an important role in the development of airway remodeling in asthma, and they can differentiate into mesenchymal cells through epithelial-mesenchymal transition.This article reviews the signaling pathways involved in epithelial-mesenchymal transition, such as TGF-β 1 signaling pathways, Wnt/β-catanin signaling pathway and sonic hedgehog signaling pathway, to further elucidate the molecular mechanisms in airway remodeling in asthma.It provides a new perspective for the study of the pathogenesis of asthma and the development of new, effective and safe targeted therapy.

Fuganlin oral liquid ameliorates airway remodeling through TGF-β1/Smad3 signaling pathway in asthmatic mice / 中国药理学通报

Aim To explore the effect of Fuganlin on airway remodeling in obese asthmatic mice and its mechanism.Methods A model of chronic airway inflammation in C57 BL/6 mice with obese asthma induced by OVA and high-fat diet was established,and treated with Fuganlin 5.86,11.72 and 23.44 g·kg-1 by gavage.After the last challenge,the respiratory system resistance(Rrs),respiratory system elasticity(Ers),and respiratory system compliance(Crs)were measured with a lung function oscillator; the total number of white blood cells in whole blood was measured; tissue HE and MASSON staining were employed to observe the pathological changes.ELISA was used to detect the levels of IgE in serum and the levels of TGF-β1,Smad3 and SP in lung tissues; IHC was used to detect the expression levels of Smad3,SARA and protein in lung tissues.Results Fuganlin reduced the increase in the number of white blood cells in blood and inhibited the content of IgE in serum.Fuganlin could reduce the Rrs and Ers,enhance the Crs and regulate the respiratory function.Histopathological results showed that Fuganlin could reduce inflammatory cell infiltration and collagen deposition in the chronic airway inflammation model of obese mice,and inhibit bronchial mucosal proliferation; ELISA results showed that Fuganlin inhibited the expression of TGF-β1,Smad3,and SP; IHC results showed that Smad3 and SARA protein expression decreased.Conclusions The anti-obesity asthma effect of Fuganlin may help to improve respiratory function,control airway inflammation,and antagonize airway remodeling.

Angiotensin-converting enzyme 2 particapates in ozone-induced lung inflammation and airway remodeling in mice / 南方医科大学学报

OBJECTIVE@#To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice.@*METHODS@#Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation.@*RESULTS@#Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine.@*CONCLUSION@#ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.

Correlation Between microRNA and Bronchial Asthma and Regulatory Mechanism of Chinese Medicine： A Review / 中国实验方剂学杂志

Bronchial asthma is a common heterogeneous chronic inflammatory disorder of airways characterized by airway hyperreactivity， mucus hypersecretion， and airflow obstruction. The incidence of asthma has been on the rise worldwide， and about 45.7 million adults in China suffer from asthma. Asthma is considered a costly disease， resulting in a significant economic and social burden. microRNAs （miRNAs） are long noncoding RNAs that regulate gene expression. They play a role in asthma through their activity in multiple immune and non-immune cell subsets. They impact multiple facets of critical cell function including cell survival， proliferation， and differentiation， which in turn induce the occurrence of airway spasm， mucus hypersecretion， and asthma symptoms. Traditional Chinese medicine has a long history in the treatment of asthma. Over the past a few decades， a growing number of herbs have proven effective in treating asthma in clinical trials or asthma inflammation in animal models. Chinese medicine has the features of multiple components and multiple targets. Evidence suggests that Chinese medicine and components of Chinese medicine can regulate immune homeostasis， improve airway inflammation and airway remodeling by modulating microRNA expression for asthma treatment. However， there is a lack of systematic and detailed reviews on the regulation of asthma-related microRNA expression by Chinese medicine. The article aims to review the correlation between microRNAs and asthma in animal experiments and clinical trials in recent years， as well as the mechanism of microRNA regulation by Chinese medicine in the treatment of asthma， with the intention of providing a reference for basic research and clinical application.

Management of Airway Remodeling in a Mouse Model of Allergic Airways Inflammation Using Extracellular Vesicles from Human Bone Marrow-Derived Mesenchymal Stromal Cells

Abstract: Asthma is a chronic respiratory disease affecting 300 million people worldwide. It results in several structural changes in the airways, which are minimally accessible in clinical practice. Cell therapy using mesenchymal stromal cells (MSCs) is a promising strategy for treating asthma due to the paracrine activity of MSCs, which influences tissue regeneration and modulates the immune response. Studies using extracellular vesicles (EV) released by MSCs have demonstrated their regenerative properties in animal models. The aim of this study was to evaluate the potential of EVs isolated from human bone marrow MSCs (hBM-MSCs) to control lung tissue remodeling in ovalbumin-induced allergic asthma in Balb/c mice. We isolated hBM-MSCs from a single donor, expanded and characterized them, and then isolated EVs. Asthma was induced in 43 male Balb/c mice, divided into four groups: control, asthmatic (AS), asthmatic plus systemic EVs (EV-S), and asthmatic plus intratracheal EVs (EV-IT). Upon completion of asthma induction, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S). Seven days after, we performed bronchoalveolar lavage (BAL) and the total nuclear cells were counted. The animals were euthanized, and the lungs were collected for histopathological analysis of the airways. The EV-S group showed improvement in only the total BAL cell count compared with the AS group, while the EV-IT group showed significant improvement in almost all evaluated criteria. Therefore, we demonstrate that the local application of EVs derived from hBM-MSCs may be a potential treatment in controlling asthma.

Pharmacological blockade of protease-Activated Receptor 2 improves airway remodeling and lung inflammation in experimental allergic asthma

Abstract Protease-activated receptors (PARs) are metabotropic G-protein-coupled receptors that are activated via proteolytic cleavage of a specific sequence of amino acids in their N-terminal region. PAR2 has been implicated in mediating allergic airway inflammation. This study aims to study the effect of PAR2 antagonist ENMD1068in lung inflammation and airway remodeling in experimental asthma. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with ENMD1068 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs were removed at different time intervals after OVA challenge to analyze inflammation, airway remodeling and airway hyperresponsiveness. Ovalbumin promoted leukocyte infiltration into BALF in a PAR2-dependent manner. ENMD1068 impaired eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in the lung parenchyma into BALF and reduced the loss of dynamic pulmonary compliance, lung resistance in response to methacholine, mucus production, collagen deposition and chemokine (C-C motif) ligand 5 expression compared to those in OVA-challenged mice. We propose that proteases released after an allergen challenge may be crucial to the development of allergic asthma in mice, and PAR2 blockade may be useful as a new pharmacological approach for the treatment of airway allergic diseases.

Progress of Experimental Research on Effect of Traditional Chinese Medicine on Proteins Associated Asthmatic Airway Remodeling / 中国实验方剂学杂志

Airway remodeling is an important pathological basis of asthma， and also the main reason for the difficulty in asthma therapy. By referring to the experimental reports on the treatment of airway remodeling in asthma with traditional Chinese medicine （TCM） in recent years， the authors comprehensively analyzed the effect of TCM on proteins related to airway remodeling in asthma， and it was found that TCM could regulate the signal pathway related proteins （such as transforming growth factor-β1/Smads， extracellular signal-regulated kinase and Wnt/β-catenin）， structural proteins （such as α-smooth muscle actin， collagen， osteopontin and fibrin） and gene regulatory proteins （such as matrix metalloproteinase-9， vascular endothelial growth factor， B lymphoma cell-2 related X protein）， and participate in the regulation of airway remodeling signaling pathway， tissue structure homeostasis and gene expression， so as to inhibit airway remodeling in asthma. In conclusion， TCM can improve the pathological morphology of airway remodeling and delay the progress of airway remodeling by controlling the corresponding proteins. At present， however， a lot of studies are limited to single Chinese herbal or TCM extract in animal experiments， and there is a lack of clinical research. It is suggested to establish a systematic and multi-level study on the mechanism of TCM for treating airway remodeling in asthma based on the theory of TCM， so as to provide a better reference for clinical practice.

The anti-asthma effect of Mahuang decoction based on P38 MAPK/NF-KB signaling pathway and its mechanism / 中国药理学通报

Aim To explore the intervention effect of Mahuang decoction on airway remodeling and airway hyperresponsiveness in asthmatic rats based on the p38MAPK/NF-KB signaling pathway. Methods Network pharmacology was used to screen the potential signaling pathway of Mahuang decoction in treating asthma. The asthma model was replicated, and the airway reactivity and the pathologic changes of lung tissues of rats were observed. The concentrations of related indexes in rat serum and the expressions of key genes in murine pulmonary tissues were assessed. Results The results of network pharmacology identified 186 candidate targets, and pathway analysis showed that the treatment mechanism for asthma mainly involved Toll like receptor, mitogen activated protein kinase (MAPK), T cell receptor and so on. Mahuang decoction reduced the airway mucus secretion, attenuated the subcutaneous collagen deposition in the airway, and decreased the airway reactivity significantly. It also obviously inhibited the concentrations of VEGF, TGF-ßl, ET - 1, OPN and bJ-GF in rat serum, and the mRNA expressions of p38MAPK, NF-i

Correlation between airway remodeling and lung function in adult-onset eosinophilic asthma / 西安交通大学学报(医学版)

【Objective】 To investigate the airway parameters of adult-onset eosinophilic asthma （EA） and analyze the correlation between airway remodeling and lung function by quantitative CT. 【Methods】 From March 2015 to November 2016， totally 94 subjects from the “FACT-Digital Lung” Multi-research Center were divided into three groups： 30 normal subjects， 33 EA patients and 31 non-eosinophilic asthma （NEA） patients. We measured and recorded the bronchial parameters of RB1， LB1+2， RB10， and LB10， and small airway disease parameters. The indicators for quantitative evaluation of bronchial parameters include lumen area （LA）， wall thickness （WT）， wall area （WA）， and wall area percentage （WA%）. The parameters for the quantitative assessment of small airway disease included the percentage of inspiratory voxels below -950HU （IN-950）， the mean lung density （MLDin）， and the whole volume of the lung in inspiration （Vin）. Pearson or Spearman rank correlation analysis was used to evaluate the correlation between these parameters and lung function. 【Results】 The differences in LA/BSA， WT/√BSA， and WA/BSA between the three groups were statistically significant （P<0.05）. FEV1% had a significant correlation with IN-950 and MLDin （P<0.01）. FEV1/FVC had a significant correlation with Vin， IN-950， and MLDin （P<0.01）. EOS counts were positively related to IN-950 （r=0.343， P=0.011）， while EOS had a negative correlation with FEV1% （r=－0.343， P=0.015）. 【Conclusion】 With the increase of eosinophils counts in peripheral blood， the airway's stenosis in asthma patients gradually increased， and the extent of airflow limitation steadily increased. The IN-950 may be a sensitive imaging biomarker for evaluating the small airway disease in adult-onset eosinophilic asthma patients.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis / Citologia do lavado nasal e alterações histopatológicas na mucosa nasal de pacientescom rinite

Abstract Introduction The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. Objective To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. Methods Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. Results Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n = 36) and non-allergic rhinitis (n = 20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. Conclusion In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Resumo Introdução A extensão da lesão epitelial na rinite alérgica e não alérgica e sua associação com alterações inflamatórias no lavado nasal ainda não estão esclarecidas. Objetivo Verificar a relação entre o processo inflamatório no lavado nasal, extensão da lesão epitelial e espessamento da membrana basal na mucosa nasal de pacientes com rinite; determinar o ponto de corte do percentual de eosinófilos no lavado nasal associado à presença de atopia. Método Foram selecionados pacientes com rinite e indicação de septoplastia e (ou) turbinectomia por hipertrofia de conchas nasais, os quais foram submetidos aos testes cutâneos alérgicos, lavado nasal com determinação das concentrações de albumina, interleucina-8 (IL-8), contagem total e diferencial de células, análise da extensão da lesão epitelial, e grau de espessamento da membrana basal por meio de histopatologia da mucosa. Resultado Foram estudados 56 pacientes, mediana de 24,5 anos com diagnóstico de rinite alérgica (n = 36) e rinite não alérgica (n = 20). Nos atópicos os testes cutâneos alérgicos foram positivos para D. pteronyssinus em 35 (97,0%) e L. perenne em 18 (50,0%). Atópicos apresentaram maior índice de escore clínico para rinite em comparação a não atópicos. A contagem total de células, neutrófilos e níveis de albumina e IL-8 não foi diferente entre o lavado nasal de atópicos e não atópicos. O ponto de corte da contagem de eosinófilos no fluido nasal para a distinção de rinite alérgica e rinite não alérgica foi de 4%. Algum grau de lesão epitelial foi mais frequente em pacientes com rinite alérgica (94%) do que em pacientes com rinite não alérgica (65%). Na presença de espessamento da membrana basal, como marcador de remodelamento, não houve diferença no lavado nasal entre pacientes com rinite alérgica e não alérgica. Conclusão Nesta casuística, 4% foi o ponto de corte do número de eosinófilos no lavado nasal, para diferenciação de atopia. Remodelamento da via aérea superior pelo espessamento da membrana basal revelou infiltrado semelhante de células inflamatórias no lavado nasal, independentemente da presença de atopia.

Comparison of mild-to-moderate chronic obstructive pulmonary disease and asthma with quantitative CT / 中国医学影像技术

Objective: To investigate the differences of proximal airway structure and CT pulmonary function between steady mild-to-moderate chronic obstructive pulmonary disease (COPD) and asthma patients. Methods: Thirty patients with mild-to-moderate COPD (mtmCOPD group), 30 patients with mild-to-moderate asthma (mtmAs group) and 30 healthy controls (normal control group) underwent low-dose paired inspiratory and expiratory CT scans and quantitative analysis. The differences of airway parameters, emphysema index and air trapping index were analyzed among 3 groups. Results: The mean lumen area (LA)/ body surface area (BSA) of the proximal airway of both mtmCOPD group and mtmAs group ([10.93±2.58]mm2/m2, [10.81±3.20]mm2/m2) were lower than that of normal control group ([12.56±2.98]mm2/m2), and statistically significant difference was found between mtmAs group and normal control group (P=0.04). The mean WA% of both mtmCOPD group and mtmAs group ([63.02±2.34]%, [63.85±2.48]%) were higher than that of normal control group ([61.55±3.54]%), while statistically significant difference was observed between mtmAs group and normal control group (P<0.01). The paired inspiratory and expiratory VI-910 (%) and VI-950 (%) of mild-to-moderate COPD were higher than those of healthy controls (all P<0.01). The expiratory absolute value of mean lung density (MLD), expiratory VI-856 (%) and MLD E/I of mtmCOPD group were also higher than those of normal control group (all P<0.05). There was no significant difference in airway structural parameters, emphysema nor air trapping index between mtmCOPD group and mtmAs group. Conclusion: The lumen area of proximal bronchus of mild-to-moderate COPD and asthma patients were both smaller than that of healthy controls to a certain extent. Meanwhile, their percentage of proximal airway wall area were both larger than that of healthy controls, which were more obviously in patients with mild-to-moderate asthma. There were obvious emphysema and air trapping in mild-to-moderate COPD patients than in healthy subjects.

Effect of Dialectical Therapy of Bufeitang Combined with Shengesan and Fujiu Application on COPD at Stable Period and Lung-kidney Qi Deficiency Syndrome / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of dialectical therapy of Bufeitang combined with Shengesan and Fujiu application on chronic obstructive pulmonary disease (COPD) and lung-kidney Qi deficiency syndrome, and its effect on inflammatory damage and airway remodeling. Method::One hundred and thirty-four patients were randomly divided into control group (66 cases) and observation group (68 cases) by random number table. Patients in control group got spiriva by powder inhaler, 1 grain/time, 1 time/day, and salmeterol xinafoate and fluticasone propionate powder for inhalation for spray as appropriate, 1 suction/time, 1-2 times/days, for a continued 12 months. In addition to the therapy of control group, patients in observation group were also given Fujiu application at two-tailed acupoints of Feiyu, Piyu and Shenyu for the first day of the every San Fu and San Jiu, and dialectical therapy of Bufeitang combined with Shengesan were given at the first day of San Fu and San Jiu for 2 months. The course of treatment was 12 months. Before and after treatment, FEV1% of self-assessment questionnaire of patients with COPD (CAT), 6-min walking distance, St George's respiratory questionnaire (SGRQ), severity of dyspnea (mMRC) and index of BODE were assessed. And levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase inhibitor-1 (TIMP-1) were detected. Result::After treatment, scores of CAT, the total score of SGRQ, scoring of each dimension and index of BODE in observation group were all lower than that in control group (P<0.01), while FEV1% was higher than that in control group (P<0.01). And 6-min walking distance was more than that in control group (P<0.01), and the numbers of acute exacerbations were less than that in control group (P<0.01). The severity of dyspnea was lighter than that in control group (Z=2.047, P<0.05). And levels of MMP-9, TNF-α, IL-6 and ratio of MMP-9/TIMP-1 were lower than those in control group (P<0.01), whereas the level of TIMP-1 was higher than that in control group (P<0.01). Conclusion::Dialectical therapy of Bufei decoction combined with Shenge powder and Fujiu application can alleviate the current symptoms of dyspnea, improve exercise tolerance, quality of life and pulmonary function, reduce the number of acute exacerbations, relieve inflammation damage and airway remodeling. The comprehensive clinical efficacy is better than that of conventional western medicine.

Effects of Maxing-Shigan decoction on airway remodeling and expression of MMP-9 and TIMP-1 in lung tissues of asthmatic mice / 中国病理生理杂志

AIM:To investigate the effects of Maxing-Shigan decoction on airway remodeling and expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the lung tissues of asthmatic mice, and to explore its possible mechanism in treatment of asthma.METHODS:The BALB/c mice were divided into blank control group, model group, low-dose Maxing-Shigan decoction group, middle-dose Maxing-Shigan decoction group, high-dose Maxing-Shigan decoction group and positive control group.The mice were sensitized and challenged with ovalbumin to establish asthma model.The mice in blank control group and model group were given saline by oral administration before 30 min of suscitation.The mice in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups were given Maxing-Shigan decoction at 5.0 g/kg, 10.0 g/kg and 20.0 g/kg, respectively, by oral administration before 30 min of suscitation.The mice in positive control group was given dexamethasone at 0.005 g/kg by oral administration before 30 min of suscitation.After consecutive administration for 7 d, the variations of airway responsiveness, the percentage of the goblet cells, the collagen deposition, and the eosinophil (EOS) counts in bronchoalveolar lavage fluid (BALF) of each group were observed.The protein levels of MMP-9 and TIMP-1 in the lung tissues were determined by ELISA and Western blot.The mRNA expression of MMP-9 and TIMP-1 was detected by RT-qPCR.RESULTS:Compared with blank control group, the airway responsiveness, the goblet cell percentage, the collagen deposition, the EOS counts in BALF, the protein levels of MMP-9 and TIMP-1, and the mRNA expression of MMP-9 and TIMP-1 were significantly increased in model group (P<0.01).Compared with model group, all of the indexes were reversed in low-dose, middle-dose and high-dose Maxing-Shigan decoction groups and positive control group (P<0.05 or P<0.01).CONCLUSION:Maxing-Shigan decoction improves airway remodeling in asthma model mice by down-regulating the expression of MMP-9 and TIMP-1.

Role of microRNA-21 in airway remodeling in asthmatic mice / 国际儿科学杂志

Objeetive Airway remodeling is an important pathological feature of asthma.This study is to investigate the role of microRNA-21 (miR-21) in airway remodeling in asthmatic mice.Methods A total of 16 female BALB/c mice were randomly divided into control group and asthma model group.Mice were sensitized and challenged by ovalbumin to establish a murine model of asthma.The mice in the normal control group were intraperitoneally injected with phosphate buffered saline for sensitization and given a phosphate buffered saline inhalation for the challenge.Twenty-four hours after the last aerosol inhalation,lung tissues of mice were sampled and subjectd to Western blot for testing expression of TGFβ type Ⅱ receptor,Smad7,and Collagen Type Ⅰ (COL Ⅰ) in lung tissue of mice of each group.Quantitative real-time PCR was used to test miR-21 expression in lung tissue of mice of each group.Target gene prediction software (TargetScan) was used to predict target gene of miR-21.293T cell was used to conduct dual-luciferase reporter gene assay for verification of miR-21 target gene.Results Compared with control group,asthma group had increased expression of COL Ⅰ protein and miR-21 in lung tissue (t =11.94,P ＜ 0.05;t =23.05,P ＜ 0.05).Smad7 and TGF-βR Ⅱ were target genes of miR-21.Conclusion miR-21 down-regulates Smad7,a target gene of miR-21,activates the TGFβ/Smad signaling pathway,and promotes airway remodeling,indicating that miR-21 may be a therapeutic target for the treatment of airway remodeling in asthma.