Re-evaluation for systematic reviews of traditional Chinese medicine in the treatment of chronic bronchitis.

BACKGROUND: Chronic bronchitis (CB) is a common clinical chronic respiratory disease, which has a high incidence in the middle aged and elderly population. With the development of the disease, the number of acute attacks becomes more and more frequent, which leads to the continuous decrease of lung function. If not treated in time, it will lead to a variety of complications and seriously affect the quality of life of patients. Traditional Chinese medicine (TCM) or TCM combined with western medicine is highly effective in the treatment of CB disease. In recent years, there are many systematic reviews on the use of TCM therapy in the treatment of CB, and the efficacy and safety of TCM in the treatment of CB diseases are evaluated. The aim of this study was to re-evaluate the Meta analysis/Systematic reviews (MAs/SRs) of TCM for the treatment of CB, aiming to provide a clinical basis for the treatment of CB by TCM. METHODS: Retrieval among Chinese and English databases such as China National Knowledge Infrastructure, Wanfang database, China Scientific Journals Database, SinoMed, PubMed, Web of Science, The Cochrane Library and EMbase, etc. were conducted within the duration from database establish Tion date to March 2023.The included research was independently conducted by 2 researchers for literature screening, data extraction, and quality evaluation. The AMSTAR 2 scale was used to evaluate the quality of the report, the PRISMA 2020 statement evaluated the quality of the report, the ROBIS tool evaluated the risk of bias, and the GRADE quality evaluation tool evaluated the quality of the evidence. RESULTS: Fifteen MAs/SRs were included, for a total of 224 studies involving 20,710 patients with CB. The 15 studies included in AMSTAR 2 are of very low quality. The ROBIS evaluation results showed that 8 MAs/SRs were considered to have high risk and 7 with low risk. The PRISMA 2020 report quality showed evaluation results of the included studies scores between 24 and 30, among them 13 with high quality and 2 with low quality. The GRADE system results showed that, within 70 outcome indicators, only 14 of them have moderate quality for evidence, with 31 for low quality, 25 for very low quality, and none for high quality. CONCLUSION: The MAs/SRs methodological quality of using TCM for treatment CB is generally poor, the quality of reports as well as evidence are generally low, and the risk of bias is high, therefore we should treat these results with caution.

Explore bioactive ingredients and potential mechanism of Houpo Mahuang decoction for chronic bronchitis based on UHPLC-Q exactive orbitrap HRMS, network pharmacology, and experiment verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic bronchitis (CB) affects a growing number of people and may be linked to lung function impairment. The traditional Chinese medicine formula Houpo Mahuang Decoction (HPMHD) has been used for clinical treatment of respiratory diseases for thousands of years. Until now, its bioactive ingredients, potential targets and molecular mechanism remain unclear. AIM OF THE STUDY: To investigate the effect of HPMHD on the treatment of CB and explore the bioactive ingredients and possible mechanisms of HPMHD against CB. MATERIALS AND METHODS: UHPLC-Q Exactive Orbitrap HRMS was performed to analyze the chemical components of HPMHD. The mechanism of multiple components, targets and pathways of HPMHD in the treatment of chronic bronchitis were explored by network pharmacology. Additionally, CB mice model induced by lipopolysaccharide (LPS) and smoking was used to evaluate the anti-chronic bronchitis activity of HPMHD in vivo. Pulmonary pathology was determined by hematoxylin and eosin (H&E) measurement. The levels of TNF-α and IL-6 in lung were measured by ELISA. The immunofluorescence experiments were carried out for the expression of IL-1ß, TNF-α, IL-6 and NF-κB p-P65/P65 in lung. Western blot assays were performed to quantify and visualize the protein expression of NF-κB p-P65/P65 in mice lung. RESULTS: Data showed that 79 compounds were identified in HPMHD. The network pharmacology results showed 53 compounds were hinted their effectivity for the treatment of chronic bronchitis with HPMHD, such as ephedrine, schisantherin A, and honokiol. The main targets were predicted as 37 genes, including TNF, TP53, IL6 and so on. HPMHD ameliorated lung damages in mice and inhibited the NF-κB signaling pathway, one of the pathways plotted by KEGG pathway enrichment analysis, by reducing IL-1ß, TNF-α and IL-6 expression and significantly downregulating the NF-κB p-P65/P65. CONCLUSION: In summary, the complex chemical components of HPHMD was successfully elucidate by UHPLC-Q Exactive Orbitrap HRMS. The study based on network pharmacology and experiment verification indicated that HPMHD can decreased inflammatory response in lung to treat CB. The underlying mechanism may be related to the reduction of inflammation by down-regulated the NF-κB pathways.

Efficacy and Safety of N-Acetylcysteine for Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Background: Patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis are associated with poor clinical outcomes. N-acetylcysteine (NAC) is a widely used therapeutic option for such patients; however, the clinical efficacy of NAC has not been conclusively determined. We hypothesized that high-dose oral NAC can improve the clinical outcomes for patients with concurrent chronic bronchitis and COPD. Objective and Methods. This was a randomized, double-blind, placebo-controlled trial evaluating the efficacy of high-dose NAC for COPD patients with concurrent chronic bronchitis. Study participants were randomized into two groups and administered with NAC (900 mg) twice daily or matching placebo for 3 months. Then, respiratory health status was evaluated using the St. George's Respiratory Questionnaire (SGQR), which was set as the primary end point. Results: A total of 143 COPD patients with chronic bronchitis were screened, and as a result, only 100 patients were enrolled in this study (50 participants were randomized to receive placebo, and others were randomized to receive NAC). After treatment, differences in SGQR scores between the placebo and NAC groups were not significant. Moreover, differences in secondary end points between the two groups after treatment were insignificant. Discussion. High-dose NAC has no marked clinical benefits for COPD patients with concurrent chronic bronchitis.

[Effect of fresh Phragmitis Rhizoma on airway inflammation in chronic bronchitis based on TGF-ß signaling pathway].

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-ß(TGF-ß) and interleukin-6(IL-6) levels. The protein expression of TGF-ß, IL-1ß 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-ß and IL-1ß, and Western blot was employed to determine the protein levels of TGF-ß and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-ß and IL-6 levels, down-regulated the protein levels of TGF-ß, IL-1ß, 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-ß and IL-6 as well as the mRNA level of TGF-ß 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-ß signaling pathway.

[Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats].

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1ß and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

Effects of a Mixture of Ivy Leaf Extract and Coptidis rhizome on Patients with Chronic Bronchitis and Bronchiectasis.

BACKGROUND: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. METHODS: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George's Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. RESULTS: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37-88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16; p < 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45; p < 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. CONCLUSIONS: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.

Effect of SGRQ-Defined Chronic Bronchitis at Baseline on Treatment Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate.

BACKGROUND: Chronic bronchitis (CB) is one of the conditions that contribute to chronic obstructive pulmonary disease (COPD). Despite its widespread prevalence among patients with COPD and overall negative impact on treatment outcomes, the effect of CB on the efficacy of bronchodilator therapy has not been evaluated. The objective of this post hoc analysis is to assess the effect of nebulized glycopyrrolate (GLY) on lung function and health-related quality of life outcomes in patients with St George's Respiratory Questionnaire (SGRQ)-defined CB at baseline. METHODS: Pooled data from the replicate, 12-week GOLDEN 3 and 4 studies (N=861) were grouped by CB status at baseline. The endpoints reported are changes from baseline in trough forced expiratory volume in 1 second (FEV1), SGRQ and EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (EXACT-RS) scores. Safety of GLY was evaluated by monitoring the incidence of adverse events (AEs). RESULTS: Following 12 weeks of treatment, GLY 25 µg twice-daily (BID) resulted in placebo-adjusted improvements from baseline in FEV1 of 77.1 mL and 124.4 mL in the CB and non-CB groups, respectively (p<0.0001 vs placebo in both groups). Significant improvements in SGRQ total scores were observed with GLY 25 µg BID compared with placebo, regardless of baseline CB status. Although EXACT-RS improvements were noted in both CB and non-CB groups, significant improvements were observed only in the CB group. GLY 25 µg BID was generally well tolerated through 12 weeks of treatment, with a low incidence of AEs. CONCLUSION: Treatment with nebulized GLY 25 µg BID for 12 weeks resulted in significant improvements in lung function and SGRQ total scores, compared with placebo. Significant improvements in EXACT-RS total scores were observed only in the CB group. Together, these results support the use of GLY 25 µg BID in patients with COPD, regardless of their CB status.

Anti-type I allergic effects of Jing-Fang powder extracts via PI3K/Akt pathway in vitro and in vivo.

Jing-Fang powder (Schizonepeta tenuifolia Briq. and Saposhnikovia divaricata (Turcz.) Schischk.) was used to treat chronic bronchitis, asthma and chronic urticaria. Based on the preliminary results of screening research on the antiallergic effective parts of Jing-Fang powder, its ethyl acetate extract fractions (JFEE) and isolate D (JFEE-D) showed the best anti-allergic effect. RBL-2H3 cell activation degranulation model and mice passive cutaneous anaphylaxis (PCA) reaction model were used to investigate the effects and mechanisms of JFEE and JFEE-D on IgE-mediated type I allergic reactions. LC-MS was utilized to determine the composition of JFEE and JFEE-D. We found that JFEE and JFEE-D significantly reduced ß-HEX, histamine, IL-4, IL-6 levels in cell supernatants, and improved the degree and morphology of cell degranulation. JFEE and JFEE-D significantly inhibited the increase of ear vascular permeability and abnormal increase of serum IgE, TNF-α, IL-6 levels. JFEE and JFEE-D inhibited mRNA expression of PI3K and Akt and down-regulated protein expression of PI3K, Akt, p-Akt, and PLCγ1 in sensitized RBL-2H3 cells. The combined use of JFEE and JFEE-D with pathway inhibitor Wortmannin revealed synergistic down-regulation of PI3K, Akt, and p-Akt protein expression. The combined use of pathway agonist IGF-1, JFEE and JFEE-D down-regulated increase of p-Akt/Akt protein expression. Moreover, JFEE and JFEE-D significantly inhibited protein expression of PI3K, p-Akt and PLCγ1 in PCA model mice. These results show that JFEE and JFEE-D inhibit type I allergic reactions by inhibiting PI3K/Akt signaling pathway.

Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats / 中国中药杂志

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

The Effect of Different Water Extracts from Platycodon grandiflorum on Selected Factors Associated with Pathogenesis of Chronic Bronchitis in Rats.

The aim of this study was to assess the activity of extracts from Platycodon grandiflorum A. DC (PG) in a model of chronic bronchitis in rats. The research was carried out on three water extracts: E1 - from roots of field cultivated PG; E2 - from biotransformed roots of PG; E3 - from callus of PG. The extracts differed in saponins and inulin levels-the highest was measured in E3 and the lowest in E1. Identification of secondary metabolites was performed using two complementary LC-MS systems. Chronic bronchitis was induced by sodium metabisulfite (a source of SO2). Animals were treated with extracts for three weeks (100 mg/kg, intragastrically) and endothelial growth factor (VEGF), transforming growth factors (TGF-ß1, -ß2, -ß3), and mucin 5AC (MUC5AC) levels were determined in bronchoalveolar lavage fluid, whereas C reactive protein (CRP) level was measured in serum. Moreover, mRNA expression were assessed in bronchi and lungs. In SO2-exposed rats, an elevation of the CRP, TGF-ß1, TGF-ß2, VEGF, and mucin was found, but the extracts' administration mostly reversed this phenomenon, leading to control values. The results showed a strong anti-inflammatory effect of the extracts from PG.

Effect of myrtol on chronic bronchitis or chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The key to the management of chronic obstructive (CB) and chronic obstructive pulmonary disease (COPD) is to control symptoms of the disease and to prevent deterioration in the health of affected patients. Myrtol has been proved to be effective in treating the symptoms of patients with CB and COPD and preventing the deterioration in their health. However, there has been no systematic review of the efficacy and safety of myrtol in the treatment of CB or COPD. The purpose of this study is going to evaluate the effects of myrtol on the management of CB or COPD based on randomized controlled trials. METHODS: Electronic literature and other ongoing studies will be searched before November 31, 2019. Randomized controlled trials that report the use of myrtol in the treatment of CB or COPD (in the absence and presence of concurrent treatments) will be selected for inclusion regardless of language. Primary outcomes will include cumulative numbers of exacerbation events and the number of days of disability including days in bed, days off work due to breathing complications, and days on which the participant was unable to undertake normal activities due to breathing complications. Study selection, data extraction, and deviation the derivation risk assessment will be carried out by 2 independent investigators. Meta-analysis will be carried out by the RevMan5.3 software. RESULTS: The study will provide summary results for estimating the efficacy and safety of myrtol for future treatments of CB or COPD. CONCLUSIONS: This systematic review will determine if myrtol is an effective and a safe intervention on the symptoms and the prevention of exacerbation of CB or COPD. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study because no identifying patient data will be used. The review will be published as an article or a conference presentation in a peer-reviewed journal. REGISTRATION: OSF registration number: DOI 10.17605/OSF.IO/PXRBV.

Anti-inflammatory effects of Samsoeum, a Korean medicine for health insurance, on chronic bronchitis caused by lipopolysaccharide in rats.

BACKGROUND: Samsoeum (SSE), a Korean medicine, has been used to treat upper respiratory infection including residual coughs after catching a cold, and colds in patients with gastrointestinal disorder. In this study, we investigated the inhibitory effect of SSE against lipopolysaccharide (LPS)-induced bronchitis and characterized its optimal dosing range based on the improvement of SSE concentrations. MATERIALS AND METHODS: Male Sprague Dawley rats were intra-nasally administered LPS on day 0, 3 and 6. 2 g kg-1 dose of SSE for rat was determined by the human equivalent dose formula and orally administered once a day from day 3 to day 6. To clarify the optimal administration dose of SSE, various doses including 0.5 (1/4 fold), 1 (1/2 fold), 6 (3 fold), 12 (6 fold), 24 (12 fold) and 36 g kg-1 (18 fold) were also orally administered. In addition, the molecular mechanism of SSE in mucin hyperproduction was investigated in LPS-sensitized A549 cells. RESULTS: Oral administration of SSE ameliorated alveolar wall thickening and inflammatory cell infiltration of lung tissues in LPS-induced bronchitis at doses of 1/4 fold, 1/2 fold and 1 fold. The total cell and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were reduced in the SSE-treated groups compared with the LPS group. In addition, 0.5, 1 and 2 g kg-1 of SSE suppressed LPS-induced mucin glycoprotein 5AC (MUC5AC) production in BALF. Furthermore, SSE treatment significantly inhibited the pro-inflammatory cytokines, resulting in the decrease of MUC5AC production by the JAK1/STAT6 signaling pathway. CONCLUSIONS: 1, 2 and 6 g kg-1 of SSE ameliorated chronic bronchitis by inhibiting LPS-induced neutrophil infiltration and MUC5AC release in BALF. These findings suggested that SSE with 0.5-3-fold of general daily intake dose would be a therapeutic agent for chronic bronchitis.

Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke-induced airway inflammation.

The total flavonoids from sea buckthorn (TFSB) exhibit a potent anti-inflammatory activity; however, the effect of TFSB on respiratory inflammatory disease is not fully known. The present study evaluated the potential of TFSB to prevent airway inflammation and the underlying mechanism. The results showed that TFSB remarkably inhibited lipopolysaccharide/cigarette smoke extract (LPS/CSE)-induced expression of IL-1ß, IL-6, CXCL1, and MUC5AC at both mRNA and protein levels in HBE16 bronchial epithelial cells. TFSB also decreased the production of PGE2 through inhibition the expression of COX2 in LPS/CSE-stimulated HBE16 cells. Furthermore, bronchoalveolar fluid and histological analyses revealed that LPS/cigarette smoke exposure-induced elevated cell numbers of neutrophils and macrophages in bronchoalveolar fluid, inflammatory cell infiltration, and airway remodeling were remarkably attenuated by TFSB in mice. Immunohistochemical results also confirmed that TFSB decreased the expression of IL-1ß, IL-6, COX2, CXCL1, and MUC5AC in LPS/CS-exposed mice. Mechanistically, TFSB blocked LPS/CSE-induced activation of ERK, Akt, and PKCα. Molecular docking further confirmed that the main components in TFSB including quercetin and isorhamnetin showed potent binding affinities to MAPK1 and PIK3CG, two upstream kinases of ERK and Akt, respectively. In summary, TFSB exerts a potent protective effect against LPS/CS-induced airway inflammation through inhibition of ERK, PI3K/Akt, and PKCα pathways, suggesting that TFSB may be a novel therapeutic agent for respiratory diseases.

New lignans, sesquiterpenes and other constituents from twigs and leaves of Rhododendron micranthum.

Rhododendron micranthum is used traditionally as a remedy for the treatment of chronic bronchitis in China. To clarify the chemical basis and provide a reference for the rational use of this medicinal plant, a phytochemical study was carried out on the twigs and leaves of R. micranthum, which afforded eight new compounds (1-8) and eight known compounds (9-16). Their structures were rigorously determined by comprehensive HRESIMS, NMR and electronic circular dichroism (ECD) analyses. The anti-inflammatory activities of these compounds were evaluated. Compounds 3, 13, and 14 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-luc cells at 10 µM, while no effect on cell viability was observed.

[Meta-analysis of randomized controlled trials on effect of Tanreqing Injection combined with Western medicine on acute exacerbation of chronic bronchitis].

To systematically review the effectiveness and safety of Tanreqing Injection in treating acute exacerbation of chronic bronchitis( AECB). CNKI,Wan Fang,VIP,CBM,Medline,Cochrane Library,EMbase and Web of Science were retrieved,and randomized controlled trials for the effect of Tanreqing Injection in the treatment of acute exacerbation of chronic bronchitis were screened. The quality of the included studies was evaluated according to the Cochrane Handbook's evaluation criteria. The data was analyzed by RevMan 5.3. Totally 23 RCTs involving 1 901 patients were included,including 952 in the experimental group and 949 in the control group. The Meta-analysis demonstrated that in terms of the disappearance time of fever,the group of Tanreqing Injection combined with the conventional therapy was superior to conventional therapy group( RR =-1. 03,95%CI[-1. 45,-0. 62],P<0. 000 01); compared with the conventional therapy group,the group of Tanreqing Injection combined with conventional therapy had a higher cure rate for AECB( RR = 1. 17,95% CI[1. 13,1. 23],P < 0. 000 01). The group of Tanreqing Injection combined with levofloxacin had a higher cure rate for AECB than the levofloxacin group( RR = 1. 23,95% CI[1. 08,1. 41],P = 0. 002). The group of Tanreqing Injection combined with cefuroxime had a higher cure rate for AECB than the cefuroxime group( RR = 1. 22,95%CI[1. 05,1. 42],P = 0. 01).The group of Tanreqing Injection combined with cefoperazone sodium and sulbactam sodium had a higher cure rate for AECB than the group of cefoperazone sodium and sulbactam sodium( RR = 1. 22,95% CI[1. 04,1. 44],P = 0. 02). The outcomes of disappearance time of cough and expectoration had a huge heterogeneity,so were used for descriptive analysis. The adverse reactions mainly included skin rash,dizziness,gastrointestinal reactions. Based on the available data and the results of the analysis,the group of Tanreqing Injection combined with Western medicine has a higher cure rate for acute exacerbation of chronic bronchitis,and the effect in reducing symptoms disappearance time. In view of the limited number of included studies,small sample size and low methodological quality,the results of this study need to be confirmed with high-level clinical trials.

Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy vs triple inhaled therapy in patients with severe and very severe COPD associated with chronic bronchitis in the UK.

Purpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE2SPOND trials. Patients and methods: Patients included in the analysis had severe to very severe COPD, FEV1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year. Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087. Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population.

Quercetin, Kaempferol and Isorhamnetin in Elaeagnus pungens Thunb. Leaf: Pharmacological Activities and Quantitative Determination Studies.

Elaeagnus pungens leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti-inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed that they could considerably reduce ear-swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing significantly. These findings suggested that quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated that the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts.

Efficacy and safety of HL301 in the treatment of acute bronchitis and acute exacerbation of chronic bronchitis: a phase 2, randomized, double-blind, placebo-controlled, multicenter study.

PURPOSE: The efficacy and safety of Chinese herbs for symptomatic treatment of bronchitis is not well established. We evaluated the efficacy and safety of a combination product of seven herbs (HL301) for the treatment of acute bronchitis (AB) and acute exacerbation of chronic bronchitis (AECB) using a randomized, double-blind, placebo-controlled, multicenter trial design. METHODS: A total of 160 patients with AB or with AECB were randomized to receive placebo or one of three doses of HL301 (0.6 g/day, 1.2 g/day, or 1.8 g/day) for a total of 7 days. The primary study endpoint was the change in bronchitis severity score (BSS) from the baseline visit (visit 2) to the end of treatment visit (visit 3). Other efficacy variables were percentage BSS systemic sign efficacy after treatment and change in individual BSS parameters after treatment. FINDINGS: Changes in BSS from visit 2 to visit 3 in the three treatment groups (4.63 ± 2.24, 4.08 ± 1.63, and 4.15 ± 1.74 in the HL301 0.6 g/day, 1.2 g/day, and 1.8 g/day groups, respectively) were higher than that of the placebo group (2.88 ± 2.57) in the per protocol set (PPS) (P < .05), and it was also valid in the full analysis set (FAS). The number of participants whose symptoms (measured by BSS) improved at least 30% after treatment was higher in all three treatment groups compared to the placebo group in both the FAS and the PPS (P < .05, for all). IMPLICATIONS: Three different doses of HL301 (0.6 g/day, 1.2 g/day, and 1.8 g/day) were effective in decreasing the BSS index compared to placebo. HL301 may be effective for symptomatic treatment of both AB and AECB. LIMITATIONS: Essential components of HL301 have not been delineated in the study and patients with AB and AECB were indiscriminately enrolled in the present study. Respective evaluation of the efficacy of HL301 for AB and AECB will be necessary in the future.

Network pharmacology-based identification of key pharmacological pathways of Yin-Huang-Qing-Fei capsule acting on chronic bronchitis.

For decades in China, the Yin-Huang-Qing-Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway.

Effect of ELOM-080 on exacerbations and symptoms in COPD patients with a chronic bronchitis phenotype - a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD) long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and chronic bronchitis-dominant COPD. ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis. However, little is known about the potential effects of ELOM-080 in COPD patients. AIM: To evaluate the effect on exacerbation, cough sputum, and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis. METHODS: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 (3×300 mg) in patients with chronic bronchitis and concomitant COPD. The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period. Secondary outcomes included the total number of exacerbations (ie, cumulative occurrence of exacerbations during the study period) and the proportion of acute exacerbations necessitating an antibiotic treatment, monthly evaluations of sputum and cough symptoms, and the general state of health and a safety analysis. RESULTS: Of 260 randomized subjects, 64 patients fulfilled the inclusion criteria for COPD (ELOM-080: 35, placebo: 29). Compared to placebo, ELOM-080 reduced the percentage of subjects with at least one exacerbation (29% versus 55%, P=0.031) and a reduction in the overall occurrence of exacerbations (ELOM-080: 10, placebo: 21, P=0.012) during the winter season. The percentage of asymptomatic or mildly symptomatic patients (sputum/expectoration and cough) was consistently higher in the ELOM-080 group compared to placebo, with statistical significant differences after 2 and 3 months of treatment (2 months: ELOM-080 25%, placebo 11%, P<0.005; 3 months: ELOM-080 26%, placebo 14%, P<0.05). Likewise the subjective rating of general health status was better in the ELOM-080 group with statistically significant superiority after 2 and 3 months of treatment (2-month treatment: P=0.015; 3-month treatment: P=0.024). Tolerability results were comparable between ELOM-080 and placebo. CONCLUSION: ELOM-080 is efficacious in patients with COPD and a chronic bronchitis phenotype. Prophylactic use reduces the rate of exacerbations and improves the key symptoms of sputum and cough with a favorable long-term tolerability profile.