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      Conventional Western Treatment Combined With Chinese Herbal Medicine Alleviates the Progressive Risk of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study

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          Abstract

          Background and purpose: Lung cancer has high global incidence and mortality rates. Chronic obstructive pulmonary disease (COPD) is strongly associated with lung cancer and is an independent risk factor for lung cancer with or without smoking. Chinese herbal medicines (CHMs) are used to treat COPD. This study sought to determine whether CHM treatment effectively decreases the incidence of lung cancer in COPD patients receiving conventional Western medical treatment.

          Methods: Records obtained from the National Health Insurance Research Database (NHIRD) were used to identify 81,780 adults aged ≥18 years newly diagnosed with COPD in Taiwan between 2000 and 2010. Among them, 11,180 received CHMs after COPD diagnosis and 23,319 did not (non-CHM). After excluding patients with missing basic demographic information, each group consisted of 2,682 patients. Statistical methods analyzed the baseline characteristics for both groups and we performed a Cox proportional hazard regression analysis to examine the incidence of lung cancer. The cumulative incidence of lung cancer in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. The association between herbs and formulas was examined by NodeXL to perform a network analysis of CHM.

          Results: COPD patients using CHM had a lower risk for lung cancer (adjusted hazards ratio [aHR] = 0.36, 95% confidence interval [CI] = 0.24–0.53, p < 0.001). Older age was associated with a higher risk of lung cancer: patients aged 40–59 years (aHR = 5.32, 95% CI = 2.19–12.94, p < 0.001) and those aged ≥60 years (aHR = 16.75, 95% CI = 7.54–37.23, p < 0.001) were at significantly greater risk compared with patients aged 18–39 years. CHM use was associated with a trend for a lower cumulative incidence of lung cancer compared with non-CHM use (p < 0.001). Among the 10 most commonly used single herbs and formulas used to decrease the risk of lung cancer in COPD patients, Fritillariae thunbergii was the most commonly used single herb and Xiao Qing Long Tang the most commonly used formula.

          Conclusion: The findings from this nationwide retrospective cohort study indicate that CHM as adjunctive therapy in COPD treatment regimens may reduce the risk of lung cancer in this vulnerable patient population.

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          New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin.

          Traditional Chinese medicines have been recently recognized as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellaria also possesses potent anticancer activities. The bioactive components of Scutellaria have been confirmed to be flavones. The major constituents of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumor cell lines in vitro and inhibit tumor growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-kappaB activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumor-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation-reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C gamma 1, a key enzyme involved in Ca(2+) signaling, through H(2)O(2) signaling in malignant lymphocytes. This review is aimed to summarize the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.
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            The relationship between COPD and lung cancer

            Highlights • COPD is a risk factor for lung cancer beyond their shared aetiology. • Both are driven by oxidative stress. • Both are linked to cellular aging, senescence and telomere shortening. • Both have been linked to genetic predisposition. • Both show altered epigenetic regulation of gene expression.
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              Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies.

              The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose-response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I(2) statistic. Sixteen RCTs (14 fluticasone, 2 budesonide) with 17,513 participants, and seven observational studies (n=69,000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I(2)=0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I(2)=37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001). Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                13 September 2019
                2019
                : 10
                : 987
                Affiliations
                [1] 1Department of Chinese Medicine, China Medical University Hospital , Taichung, Taiwan
                [2] 2Management Office for Health Data, China Medical University Hospital , Taichung, Taiwan
                [3] 3School of Chinese Medicine, China Medical University , Taichung, Taiwan
                [4] 4An-Nan Hospital, China Medical University , Tainan, Taiwan
                [5] 5Chinese Medicine Research Center, China Medical University , Taichung, Taiwan
                [6] 6Research Center for Chinese Herbal Medicine, China Medical University , Taichung, Taiwan
                [7] 7Cancer Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital , Taichung, Taiwan
                Author notes

                Edited by: Rong-Rong He, Jinan University, China

                Reviewed by: Tian GuiHua, University of Chinese Medicine, China; Sijia Guo, University of Traditional Chinese Medicine, China

                *Correspondence: Sheng-Teng Huang, sheng.teng@ 123456yahoo.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work.

                Article
                10.3389/fphar.2019.00987
                6753872
                31572178
                4262827f-00a5-42f5-b214-be22f48166fa
                Copyright © 2019 Lin, Chen, Su, Lin, Lin and Huang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 March 2019
                : 31 July 2019
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 72, Pages: 12, Words: 6217
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                lung cancer,chronic obstructive pulmonary disease,chinese herbal medicine,retrospective cohort study,traditional chinese medicine

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