The Value of Multiple Medication Trials Prior to Balloon Sinuplasty in the Management of Chronic Sinonasal Disease

Abstract Introduction In patients with chronic rhinosinusitis, conservative interventions with extended medical trials are often attempted prior to procedural treatment. Balloon sinuplasty (BSP) is an established procedure for symptomatic relief from chronic rhinosinusitis. However, data suggesting the suboptimal efficacy of prolonged medication management trials, prior to BSP, is lacking. Objectives The purpose of this study was to evaluate the efficacy of prolonged medication management trials, prior to BSP, for patients with chronic rhinosinusitis. Methods A retrospective review was performed for all adults with chronic rhinosinusitis who received extended medical management prior to their BSP at two outpatient clinics, from November 1, 2013, to June 31, 2018. The patients' Sino-Nasal Outcome Test (SNOT) scores were compared between baseline, post-medication trials, and post-BSP. Results The SNOT scores of a total of 64 patients were collected. Overall, patients showed a significant worsening of symptoms during the medication management trials from baseline (p = 0.002126) but significant improvement of symptoms after undergoing BSP (p < 0.0001). Conclusions The patient symptom burden worsened and prolonged during medication management trials. The BSP procedure alone showed significant improvement in the quality of life for chronic rhinosinusitis patients, when considering their SNOT scores. The worsening of patients' symptoms during medication management may invalidate the necessity of prolonged medication management trials.

Yifei Jianpi recipe improves cigarette smoke-induced inflammatory injury and mucus hypersecretion in human bronchial epithelial cells by inhibiting the TLR4/NF-κB signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the mechanism of Yifei Jianpi recipe for improving cigarette smoke- induced inflammatory injury and mucus hypersecretion in cultured human bronchial epithelial cells.@*METHODS@#Serum samples were collected from 40 SD rats treated with Yifei Jianpi recipe (n=20) or normal saline (n=20) by gavage. Cultured human bronchial epithelial 16HBE cells were stimulated with an aqueous cigarette smoke extract (CSE), followed by treatment with the collected serum at different dilutions. The optimal concentration and treatment time of CSE and the medicated serum for cell treatment were determined with CCK-8 assay. The expressions of TLR4, NF-κB, MUC5AC, MUC7, and muc8 at both the mRNA and protein levels in the treated cells were examined with RT- qPCR and Western blotting, and the effects of TLR4 gene silencing and overexpression on their expressions were assessed. The expressions of TNF-α, IL-1 β, IL-6 and IL-8 in the cells were detected using ELISA.@*RESULTS@#At the optimal concentration of 20%, treatment with the medicated serum for 24 h significantly lowered the mRNA and protein expressions of TLR4, NF- κB, MUC5AC, MUC7, and MUC8 in CSE- exposed 16HBE cells, and these effects were further enhanced by TLR4 silencing in the cells. In 16HBE cells with TLR4 overexpression, the expressions of TLR4, NF-κB, MUC5AC, MUC7, and MUC8 were significantly increased after CSE exposure and were lowered following treatment with the medicated serum (P < 0.05). The medicated serum also significantly lowered the levels of TNF-α, IL-1β, IL-6 and IL-8 in CSE-exposed 16HBE cells (P < 0.05).@*CONCLUSIONS@#In the 16HBE cell model of chronic obstructive pulmonary disease (COPD), treatment with Yifei Jianpi recipe-medicated serum improves inflammation and mucus hypersecretion possibly by reducing MUC secretion and inhibiting the TLR4/NF-κB signaling pathway.

Study on inhibitory effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating the upstream and downstream cytokines of type Ⅱ innate lymphoid cells / 中国药房

OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

Modified Wuhutang Alleviates Airway Inflammation and Down-regulates Expression of Muc5AC， STAT3， NF-κB， and NLRP3 in Lung Tissues of RSV-infected Asthmatic Mice / 中国实验方剂学杂志

ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin （Muc） 5AC， signal transducer and activator of transcription 3 （STAT3）， nuclear factor kappa B （NF-κB）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3） in respiratory syncytial virus （RSV）-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control （CON）， asthma （ovalbumin， OVA）， RSV infection-induced asthma （OVA+RSV）， high-， medium-， and low-dose （4.08， 2.04， 1.02 g·kg-1·d-1， respectively） modified Wuhutang， and dexamethasone （Dxms， 0.1 g·kg-1d-1） groups （n=10）. The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions （1.0 × 106 PFU·mL-1， 50 μL）. Wuhutang was administrated by gavage， and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration， and then the lung tissue was stained by hematoxylin-eosin （HE） and Van Gieson （VG） for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated （p）-STAT3， STAT3， p-NF-κB， NF-κB， and NLRP3. ResultCompared with the CON group， the OVA group presented airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group， modified Wuhutang alleviated the airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition， and the high-dose group had the best performance. Compared with the CON group， the OVA group and the OVA+RSV group showed increased expression level of Muc5AC （P<0.01）. Compared with the OVA+RSV group， modified Wuhutang reduced the expression level of Muc5AC， and the reduction was significant in the high-dose group （P<0.05）. Compared with the high-dose modified Wuhutang group， Dxms lowered the expression level of Muc5AC （P<0.05）. Compared with the CON group， the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.05， P<0.01）. Compared with the OVA+RSV group， modified Wuhutang down-regulated the protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.01）. Compared with the high-dose modified Wuhutang group， the Dxms group showed up-regulated levels of p-STAT3， p-NF-κB proteins （P<0.01）. ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC， p-STAT3， p-NF-κB， and NLRP3 in RSV-infected asthmatic mice， which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.

Mechanism of Xuanfu Daizhetang in Alleviating Allergic Asthma by Inhibiting Secretion of Inflammatory Factors / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effects of Xuanfu Daizhetang on a mouse model of allergic asthma induced by ovalbumin （OVA）. MethodSixty female BALB/c mice （6-8 weeks old， SPF） were randomly divided into groups. Ten mice were assigned to the normal group and given 0.2 mL of saline， while the remaining groups received intraperitoneal injections of Al（OH）3 at 5 g·L-1 and OVA at 1 g·L-1. The mice were divided into normal group （10 mL·kg-1 saline）， OVA model group （10 mL·kg-1 saline）， dexamethasone group （OVA+DEX， 1 mg·kg-1）， OVA+ low-dose Xuanfu Daizhetang group （OVA+XL， 7.065 g·kg-1）， OVA+ medium-dose Xuanfu Daizhetang group （OVA+XM， 14.13 g·kg-1）， and OVA+ high-dose Xuanfu Daizhetang group （OVA+XH， 28.26 g·kg-1）. An OVA-induced asthma model was established in mice. Hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining methods were used to observe bronchial tissue pathological changes. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， IL-5， IL-13， IL-17A， and γ interferon （IFN-γ） in bronchoalveolar lavage fluid. Western blot was used to detect the phosphorylation of extracellular signal-regulated kinase （ERK）， p38 mitogen-activated protein kinase （MAPK）， and c-Jun N-terminal kinase （JNK） proteins in lung tissue. ResultCompared with the normal group， the OVA model group showed increased inflammatory cell infiltration in mouse alveoli， elevated levels of IL-4， IL-5， IL-13， IL-17A， IFN-γ in bronchoalveolar lavage fluid， and IgE in serum （P<0.05， P<0.01）， and promoted phosphorylation of MAPK signaling pathway-related proteins. Compared with the model group， the OVA+XL， OVA+XM， and OVA+XH groups showed reduced inflammatory cell infiltration in mouse alveoli， decreased levels of IL-4， IL-5， IL-13， IL-17A， IFN-γ in bronchoalveolar lavage fluid， and IgE in serum （P<0.05， P<0.01）， and inhibited phosphorylation of MAPK signaling pathway-related proteins. ConclusionThe results of this study suggest that Xuanfu Daizhetang has potential anti-allergic asthma activity， providing a theoretical basis for its future clinical application.

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.

Effects and mechanisms of wogonin on airway inflammation in rats with chronic obstructive pulmonary disease / 中国药房

OBJECTIVE To study the effects and potential mechanism of wogonin （Wog） on airway inflammation in rats with chronic obstructive pulmonary disease （COPD）. METHODS Eighty-four rats were randomly divided into control group， model group， Wog low-dose and high-dose groups （intragastric administration of 50， 100 mg/kg）， aminophylline group （positive control， intragastric administration of 2.3 mg/kg）， recombinant rat receptor-interacting protein kinase 1 [rRIPK1， receptor-interacting protein kinase 1 （RIPK1） activator] group （tail vein injection of 8 µg/kg）， and Wog high-dose+rRIPK1 group （intragastric administration of Wog 100 mg/kg+tail vein injection of rRIPK 8 µg/kg）， with 12 rats in each group. Except for control group， COPD model of other groups was induced by smoking combined with tracheal injection of lipopolysaccharide. Twenty-four hours after successful modeling， the rats were administered once a day for 4 weeks. The changes of peak inspiratory flow （PIF）， peak expiratory flow （PEF） and minute ventilation （MV），forced expiratory volume in one second（FEV1）/forced vital capacity（FVC） were measured after the last medication； the serum levels of interleukin 1β（IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） were measured by ELISA； the pathological changes of lung tissue in rats were observed； the apoptotic rate of pulmonary epithelial cells was detected. mRNA expressions of RIPK1， RIPK3 and mixed lineage kinase domain-like protein （MLKL）， and protein expressions of RIPK1， RIPK3 and p-MLKL were all detected in lung tissue of rats. RESULTS Compared with control group， PIF， PEF， MV and FEV1/FVC of model group were decreased significantly （P＜0.05）， while the levels of IL-1β， IL-6 and TNF- α were increased significantly （P＜0.05）； there was a large number of inflammatory cells infiltration in the lung tissue and bronchialwall thickening in model group； the apoptotic rate of pulmonary epithelial cells，mRNA expressions of RIPK1， RIPK3 and MLKL， protein expressions of RIPK1， RIPK3 and p-MLKL were increased significantly （P＜0.05）. Compared with model group， above indexes of rats were improved significantly in Wog low-dose and high-dose groups （P＜0.05）， and pathological injuries were alleviated significantly. The corresponding indexes of rats were worsened in rRIPK1 group （P＜0.05）， and pathological damage had further worsened. rRIPK1 significantly attenuated the inhibitory effect of high-dose Wog on airway inflammation and RIPK1/RIPK3/ MLKL pathway in COPD rats （P＜0.05）. CONCLUSIONS Wog may improve airway inflammation in COPD rats by inhibiting RIPK1/RIPK3/MLKL signal pathway.

Progress of soluble growth stimulating express gene 2 in children respiratory diseases / 国际儿科学杂志

Soluble growth stimulating express gene 2(sST2)is a member of Toll/IL-1 receptor superfamily.sST2 plays an important role in the occurrence and development of respiratory diseases in children.Under normal circumstances, the concentration of sST2 in serum is very low, but the level of sST2 in serum of children with respiratory diseases such as bronchial asthma and community-acquired pneumonia increased significantly.sST2 blocks the IL-33 signaling pathway in airway inflammation, so serum sST2 levels can predict the severity of childhood asthma.sST2 can also be used as a prognostic marker of community-acquired pneumonia.This paper reviews the mechanism, clinical characteristics and prognosis of sST2 in children with asthma and community-acquired pneumonia, so as to lay a foundation for guiding clinical identification and treatment of respiratory diseases in children.

Effects of Huaiqihuang Granules on airway inflammation in bronchiolitis / 中国基层医药

Objective:To investigate the effects of Huaiqihuang Granule on airway inflammation and wheezing reattack in bronchiolitis. Methods:A total of 120 patients with bronchiolitis presenting airway inflammation and wheezing reattack who received treatment in Zaozhuang Municipal Hospital and Yicheng Hospital of Traditional Chinese Medicine between January 2018 and October 2019 were included in this study. These patients randomly underwent either conventional treatment (control group, n = 60) or conventional treatment + Huaiqihuang Granule treatment (experimental group, n = 60). They received pulmonary function examinations and laboratory tests for evaluating serum and urinary inflammatory factors at admission and 2 months after discharge. They were followed up by telephone 3 months and 1 year after onset. Results:The ratio of time to reach the peak tidal expiratory flow over total expiratory time (TPTEF/TE) and the volume to peak tidal expiratory flow to total expiratory volume (VPTEF/VE) were significantly higher in the experimental group compared with those in the control group ( t = 3.13, 3.60, all P < 0.01). The ratio of tidal peak flow to tidal expiratory flow when 25% of tidal volume remains in the lungs (PF/TEF25) and functional residual capacity/kg (FRCp/kg) significantly decreased in the experimental group compared with those in the control group ( t = 3.88, 3.74, all P < 0.01). Interleukin-4 level and the ratio of interleukin-4/γ-interferon levels were significantly lower in the experimental group than in the control group ( t = 5.70, 8.93, all P < 0.01). Gamma-interferon level was significantly higher in the experimental group than in the control group ( t = 3.85, P < 0.01). There was no significant difference in urinary leukotriene E4 level post-treatment between the two groups ( t = 1.18, P > 0.05). The number of patients who had a wheezing attack again within 3 months post-treatment and the number of patients who had ≥3 wheezing attacks were significantly lower in the experimental group compared with those in the control group ( χ2 = 5.18, 6.98, P < 0.01 or 0.05). Conclusion:Huaiqihuang granule can effectively regulate the balance of the Th 1/Th 2 ratio, inhibit airway inflammation in bronchiolitis, improve pulmonary function, and reduce the number of wheezing reattacks.

Active components of Descurainia sophia improve lung permeability in rats with allergic asthma by regulating airway inflammation and epithelial damage / 中国中药杂志

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.

miR-135a inhibits airway inflammatory response in asthmatic mice via regulating JAK/STAT signaling pathway

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P<0.05). Addition of JAK inhibitor AG490 reduced airway inflammation in asthmatic mice. miR-135a agonists inhibit airway inflammation in asthmatic mice by regulating the JAK/STAT signaling pathway.

Effects of vitamin D3 adjuvant therapy on pulmonary function and airway inflammation in children with bronchial asthma / 中国基层医药

Objective:To investigate the effects of vitamin D3 adjuvant therapy on pulmonary function and airway inflammation in children with bronchial asthma, providing evidence for clinical treatment of bronchial asthma.Methods:100 children with bronchial asthma who received treatment in Xin'an International Hospital from January 2018 to June 2020 were included in this study. They were randomly assigned to receive either conventional treatments (such as bronchodilator and glucocorticoid treatments)(control group, n = 50) or conventional treatment combined with vitamin D3 adjuvant treatment (observation group, n = 50) for 9 days. Clinical efficacy and adverse reactions were compared between the two groups. Before and after treatment, forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10), and interleukin-5 (IL-5) levels were compared between the two groups. Results:Total effective rate in the observation group was significantly higher than that in the control group [94.00% (47/50) vs. 80.00% (40/50), χ2 = 4.332, P < 0.05]. After treatment, FEV 1 and FVC levels in each group were significantly increased compared with before treatment (both P < 0.05). After treatment, FEV 1 and FVC levels in the observation group were (1.47 ± 0.42) L and (2.09 ± 0.64) L, respectively, which were significantly higher than those in the control group [(1.21 ± 0.34) L, (1.85 ± 0.47) L, t = 2.137, 3.402, both P < 0.05]. After treatment, TNF-α and IL-5 levels in each group were significantly deceased (both P < 0.001), and IL-10 level was significantly increased ( P < 0.001), compared with before treatment in the same group. After treatment, TNF-α and IL-5 levels in the observation group were (0.58 ± 0.13) ng/L and (39.37 ± 3.54) ng/L, respectively, which were significantly lower than those in the control group [(0.92 ± 0.23) ng/L, (61.36 ± 5.72) ng/L], t = 9.099, 38.628, both P < 0.001]. After treatment, IL-10 level in the observation group was significantly higher than that in the control group [(215.62 ± 13.25) ng /L vs. (127.28 ± 9.27) ng/L, t = 23.115, P < 0.001]. Conclusion:Vitamin D3 adjuvant therapy for the treatment of bronchial asthma in children can help promote pulmonary function recovery and reduce airway inflammation, which is worthy of clinical application.

Progress on detection of exhaled nitric oxide in diagnosis and treatment of asthma in children / 国际儿科学杂志

Asthma is a common chronic airway inflammatory disease in children.In recent decades, the global prevalence of asthma in children has been increasing significantly.As a heterogeneous disease, asthma presents multiple phenotypes, with the type 2(eosinophilic)airway inflammation predominating in children.Currently, fractional exhaled nitric oxide(FeNO)is an internationally recognized marker of eosinophilic airway inflammation, and its value in the diagnosis and treatment of asthma in children has been gradually recognized.This article reviews the sources, detection methods, possible influencing factors of FeNO and its role in the diagnosis and treatment of asthma in children.

Clinical Efficacy of Qufeng Juanyin Decoction on Infantile Bronchial Asthma with Wind Phlegm Obstructing Lung Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Qufeng Juanyin Decoction on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack， and the regulatory effect on T helper cell 17 （Th17）/regulatory T cell （Treg） and related factors. Method:One hundred and thirty patients were randomly divided into observation group （65 cases） and control group （65 cases） by random number table. In control group， 61 cases completed the treatment， including 1 fell off or lost visit， 3 was eliminated because of breach of protocol. And in observation group， 63 patients completed the treatment， including 2 cases fell off or lost visit. Both of the groups got Budesonide suspension by atomizer， 1 mg/time， 2 times/day， and severe children were added with Terbutaline Sulfate Aerosol every morning and evening， 2 sprays/time. Patients in control group got Suhuang Zhike capsules， 2 grains/time， 3 times/day. Patients in observation group got Qufeng Juanyin Decoction， 1 dose/day. The course of treatment lasted for 7 days. Onset and mitigation times of asthma were recorded. And before and after treatment， pulmonary function was evaluated， and daily variation rate of peak expiratory flow （PEF）， first second expiratory flow as a percentage of expected （FEV₁%） and ratio of first second forced expiratory volume （FEV₁） and forced vital capacity （FVC） were recorded， and scores of syndrome of wind phlegm blocking lung and exhaled nitric oxide were detected. At the first week after the treatment， asthma control test in children （C-ACT） was made. Levels of Th17 cells， Treg cells， interleukin-17 （IL-17）， IL-6， IL-10， IL-22 and IL-35 were also detected. And the safety was evaluated. Result:Onset and mitigation times of asthma in observation group were shorter those in control group （<italic>P</italic><0.01）. The daily variation rate of PEF in observation group was lower than that in control group （<italic>P</italic><0.01）， while levels of FEV₁% and FEV₁/FVC were higher than those in control group （<italic>P</italic><0.01）. Asthma control in observation group was better than that in control group （<italic>Z</italic>=2.106， <italic>P</italic><0.05）. FeNO and score of syndrome of wind phlegm blocking lung were lower than those in control group （<italic>P</italic><0.01）. Levels of Th17， Th17/Treg， IL-17， IL-6 and IL-22 were lower than those in control group （<italic>P</italic><0.01）， whereas levels of proportion of Treg cells， IL-10 and IL-35 were higher than those in control group （<italic>P</italic><0.01）. The total effective rate in observation group was 96.83% （61/63）， which was better than 85.25% （52/61） in control group （<italic>χ</italic>²=5.141， <italic>P</italic><0.05）. And the total effective rate of traditional Chinese medicine （TCM） syndrome was 98.41% （62/63）， which was better than 86.89% （53/61） in control group （<italic>χ</italic>²=4.525， <italic>P</italic><0.05）. And there was no adverse reaction caused by Qufeng Juanyin Decoction. Conclusion:Qufeng Juanyin Decoction can shorten the course of disease， improve the lung function， regulate the expressions of Th17/Treg cells and related factors， promote the immune balance of Th17 / Treg， reduce airway inflammation and airway hyperresponsiveness， and effectively control the attack of asthma， with a good clinical efficacy and safety on bronchial asthma in children （syndrome of wind phlegm blocking lung） during the stage of attack.

Clinical Efficacy on Erchentang Combined with Sanzi Yangqintang in Treatment of Cough Variant Asthma in Children with Phlegm Evil Accumulation Lung Syndrome / 中国实验方剂学杂志

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>_{control group}=5.277， <italic>F</italic>_{observation group}=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>²=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>²=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.

Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease / 中国药科大学学报

@#Chronic obstructive pulmonary disease (COPD), characterized by airflow constraint, is a chronic respiratory disease closely related to the chronic inflammatory response of the airways and lungs to harmful gases or toxic particles, which may further develop into pulmonary heart disease and respiratory failure.At present the complex pathogenesis of COPD is considered to be the result of the interaction of a variety of genetic and environmental factors, and there is stiu no safe and effective drug for the treatment. This article reviews the pathogenesis of COPD from such aspects as oxidative stress, protease/antiprotease imbalance, immune mechanism, cell aging and cell repair mechanism, cell necrosis and autophagy,withan introduction to the potential targets and clinical research progress of related drugs, including β2 receptor agonists, muscarinic antagonists, theophylline and its derivatives, drugs targeting inflammatory mediators, protease inhibitors, kinase inhibitors, PED4 inhibitors, glandular glycoside receptor modulators,and antioxidants, which may provide some reference for the development of new drugs for COPD.

Inhibitory Effects of Qingfei Baoyuan Capsule on Airway Inflammation in Rats with Chronic Obstructive Pul- monary Disease and Its Effect on NLRP 3 Signaling Pathway / 中国药房

OBJECTIVE：To investigate inhibitory effects of Qing fei baoyu an capsule on airway inflammation in rats with chronic obstructive pulmonary disease （COPD），and its effects on NLRP 3 signaling pathway. METHODS ：Totally 60 SD male rats were randomly divided into blank control group ，model group ，dexamethasone group （positive control ，0.2 mg/kg），Qingfei baoyuan capsule high-dose ，medium-dose and low-dose groups （1 232.0，616.0，308.0 mg/kg），with 10 rats in each group. Except for blank control group ，other groups were fumigated for 28 days and given intratracheal dripping of lipopolysaccharide twice to induce COPD model. Since the 29th day after modeling ，blank control group and model group were given constant volume of normal saline intragastrically ，and administration groups were given related medicine intragastrically. The administration volume was 10 mL/kg，once a day ，for consecutive 28 days. After last administration ，the lung function was detected. The pathological changes of lung tissue were observed by HE staining. The content of interleukin- 1β（IL-1β）in bronchoalveolar lavage fluid （BALF）were detected by ELISA ，and the number of leukocytes was counted ；the expression of NLRP 3 and Cleaved caspase- 1 in lung tissue of rats were detected by Western blotting assay. RESULTS：Three，two，one，one and two rats died in model group， dexamethasone group ， Qingfei baoyuan capsule high-dose，medium-dose and low-dose groups ，respectively. Compared with blank control group ，FEV0.3/FVC of rats in # model group was significantly decreased （P＜0.01）. A large number of inflammatory cells infiltration we re found in the lung tissue ，and lung tissue lesion was obvious. The content of IL- 1β and white blood cell count in BALF，relative expression of NLRP3 and Cleaved caspase- 1 protein in lung tissue were increased significantly （P＜0.05 or P＜0.01）. Compared with model group，FEV0.3/FVC of administration groups were increased significantly （P＜0.05 or P＜0.01）；lung tissue lesion of them were improved to different extents. The content of IL- 1β and white cell count in BALF，relative expression of NLRP 3 protein（except for Qingfei baoyuan capsule low-dose group ）and Cleaved caspase- 1 protein（except for Qingfei baoyuan capsule medium-dose and low-dose groups ）in lung tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Qingfei baoyuan capsule can relieve lung tissue lesion and improve lung function in COPD model rats ，the effects of which may be associated with inhibiting inflammation reaction by inhibiting NLRP 3 signaling pathway.

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway / 医学前沿

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

Effect of different parts of Pinelliae Rhizoma Decoction against airway inflammation and analysis of effective components / 中国中药杂志

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.

Effect of fresh Phragmitis Rhizoma on airway inflammation in chronic bronchitis based on TGF-β signaling pathway / 中国中药杂志

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.