Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis

Background

The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function. The aims of this study were to investigate total mortality risks in GOLD stages 0–4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1–4.

Method

Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits. Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses. Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0–4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group. HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1–4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.

Results

The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively. The proportion of smokers among men was 50% and among women 40%. Self reported comorbidity was present in 4.6% of the men and 6.6% of the women. Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32–2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31–1.70). The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98–1.29). Among male smokers with stage 1; HR: 2.04 (1.34–3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38–7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.

Conclusion

Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2).     

Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study

Background

Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.

Methods

We divided 2703 GOLD 1–4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).

Results

There were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV₁%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.

Conclusions

Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV₁%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.     

舒适康复护理在小儿纤维塑性支气管炎的实践与研究

目的:探讨舒适康复护理在小儿纤维塑性支气管炎的临床应用与效果评价。方法:选取我院2012年3月到2013年5月小儿纤维塑性支气管炎64例,随机分成两组,每组各32例,对照组采用常规护理,实验组在对照组的基础上采用舒适康复护理,观察两组的临床效果。结果:实验组显效22例,占68.8%,有效9例,占28.1%,无效1例,占3.1%,康复有效率96.9%;对照组显效13例,占40.6%,有效12例,占37.5%,无效7例,占21.9%,康复有效率78.1%,显著差异有统计意义(P0.05)。结论:舒适康复护理可以有效地控制患儿的死亡率,值得临床推广。     

An investigation of the resolution of inflammation (catabasis) in COPD

Background

Chronic Obstructive Pulmonary Disease (COPD) is characterized by an enhanced inflammatory response to smoking that persists despite quitting. The resolution of inflammation (catabasis) is a complex and highly regulated process where tissue resident macrophages play a key role since they phagocytose apoptotic cells (efferocytosis), preventing their secondary necrosis and the spill-over of their pro-inflammatory cytoplasmic content, and release pro-resolution and tissue repair molecules, such as TGFβ, VEGF and HGF. Because inflammation does not resolve in COPD, we hypothesized that catabasis may be abnormal in these patients.

Methods

To explore this hypothesis, we studied lung tissue samples obtained at surgery from 21 COPD patients, 22 smokers with normal spirometry and 13 non-smokers controls. In these samples we used: (1) immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFβ in lung macrophages; (2) real time PCR to determine HGF, PPARγ, TGFβ, VEGF and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid mediator of catabasis.

Results

We found that current and former smokers with COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced macrophage surface expression of CD44, a key efferocytosis receptor; and, (3) similar levels of TGFβ, VEGF, HGF, PPARγ, and lipoxin A4 than smokers with normal spirometry, despite the presence of inflammation and disease.

Conclusions

These results identify several potential abnormalities of catabasis in patients with COPD.     

IBV核蛋白的表达纯化及在监测中应用

鸡传染性支气管炎病毒（Infectious bronchitis virus,IBV）是禽类一种变异性很强的冠状病毒,为获得高度纯化的IBV核蛋白,建立监测IBV抗体的方法,通过RT-PCR从IBV中扩增IBV-N基因,定向连接到表达载体pGEX-KG中,转化E. coli BL21（DE3）菌株,诱导获得表达产物,SDS-PAGE分析产物大小、Western blot分析其免疫学活性,通过亲和层析法获得高度纯化的表达蛋白,建立一种检测IBV抗体的方法,并应用于临床监测。结果显示,IBV-N基因全长1230bp,GST融合蛋白表达产物大小约为80kDa,表达量约占菌体总蛋白的25%,具有良好的免疫学活性;通过GST亲和层析柱成功获得纯化蛋白,以该蛋白包被酶标板,成功地建立了一种检测血清中IBV抗体的间接ELISA方法。研究表明重组N蛋白作为IBV诊断抗原,具有制备简便、特异性强、敏感性高、重复性好的特点,可用于该病的临床监测,为该病疫情监测、发病机制研究奠定了基础。     

基于S1蛋白的禽传染性支气管炎病毒的分子流行病学研究

禽传染性支气管炎病毒是归属于冠状病毒属的没有DNA阶段的正义单链RNA病毒,以极高的死亡率引起禽呼吸泌尿性疾病的广泛流行,每年都给家禽饲养业造成巨大的经济损失。因此开展禽传染性支气管炎病毒的分子流行病学的研究并开发出相关的疫苗时下就显得迫切而且必要。现在,我们基于序列保守且具有强免疫原性的禽传染性支气管炎病毒粒子外壳刺突S1糖蛋白开展了分子流行病学研究,并提出了用于阻断禽传染性支气管炎病毒侵染的疫苗的可行性开发策略。     

传染性支气管炎病毒江苏分离株核蛋白基因序列测定与同源性分析

将本室鸡传染性支气管炎病毒（IBV）江苏省地方分离肾型毒株JS／95／03接种鸡胚,分离、纯化病毒,提取单股RNA做为反转录－聚合酶链反应（RT－PCR）的扩增模板。用Genbank公开序列多重比较后设计一对引物,使用单管RT－PCR方法,物异扩增IBV核蛋白（N）基因5'端854bp的片段,扩增产物纯化后测,序列分析表明,IBV N基因也存在较大变异,此毒株与呼吸型疫苗株M41序列同源性最高。     

传染性支气管炎病毒(IBV)国内分离毒株的分子流行病学分析

选择9个来自我国不同地区的传染性支气管炎病毒(IBV)地方毒株,用逆转录-聚合酶链反应(RT-PCR)分别扩增出它们的完整S1基因,再将各扩增产物与T载体连接转化,筛选出相应毒株的阳性克隆,采用双脱氧链终止法测定基因序列。将这些国内分离毒株、我国常用疫苗毒株和国际上其他血清型的代表参考毒株一起,用DNAstar软件分别进行基因与氨基酸系统发生进化关系分析,结果将这些毒株分成3群：Ⅰ群内的毒株与疫苗毒株H120和M41的同源性很高,Ⅱ群内的毒株与其他毒株的同源性较低,Ⅲ群内的毒株与疫苗毒株有一定的同源性。3个群的毒株以疫苗毒株H120为核心,形成进化距离的梯度,提示弱毒疫苗的使用可能是我国IBV流行毒株的主要来源之一。分析结果还显示,我国IBV的分离毒株没有明显的时间和地理分布规律可循。     

鸡传染性支气管炎病毒H株纤突蛋白S1基因的克隆及其在毕赤酵母中表达

鸡传染性支气管炎病毒(IBV)河南分离株H,经SPF鸡胚增殖,差速离心纯化病毒,SDS-蛋白酶K法抽提病毒RNA。参照IBV Bcaudette株纤突蛋白S1基因序列设计并合成引物,以其进行RT—PCR,成功地扩增出IBV H株S1基因。扩增产物经Bst YⅠ Hae Ⅲ和Pst Ⅰ酶切分析,结果表明,IBV H株S1基因的RFLP图谱与M41株S1基因的完全一致,初步断定IBV H株为Mass血清型。将IBVH株S1基因克隆于pGEM—T载体中进行序列分析,结果表明该基因全长为1611bp(从ATG到S前体蛋白裂解位点),与标准株M41和Beaudette的S1基因序列相比较,同源率分别达到97．39％和97、27％。将IBV H株S1基因亚克隆到pPICZ—A表达载体,转化毕赤酵母中,SDS—PAGE实验证实了IBV H株S1基因在毕赤酵母中得以表达,进一步用鸡抗IBV血清做Westernblot检测．证实了表达产物的抗原特异性。     

基于网络药理学和分子对接探讨藏麻黄挥发性成分对支气管炎的作用机制

麻黄(Ephedrae Herba)具有发汗散寒、宣肺平喘、利水消肿的功效。现代研究表明麻黄对治疗支气管、哮喘有疗效。藏麻黄(Ephedra saxatilis)为西藏特有的麻黄属植物,其根、茎具有特殊香气,且目前其挥发性成分未有报道。为评价挥发性成分对支气管炎作用,用气质联用仪测定分析藏麻黄根、茎挥发性成分,并结合网络药理学和分子对接方法分析挥发性成分治疗支气管炎的关键靶点。分析检测到67个挥发性化合物,茎中含有挥发性主要成分为2,3,5,6-四甲基吡嗪(10.92%)、Z-9-十五烯醇(9.15%)、二羟基苯乙酮(7.92%);根含有的挥发性主要成分为亚油酸(7.81%)、红没药醇(7.1%)、Z-9-十五烯醇(5.98%)。有34个挥发性成分能够作用32个支气管炎疾病靶点。蛋白互作网络分析预测IL6、TNF、PTGS2、CXCL8为藏麻黄挥发性成分治疗支气管可能的潜在靶点。这些靶点与挥发性成分丁子香酚、月桂酸、反式法尼醇、α-萜品醇、榄香醇和棕榈酸6种化合物靶点相互结合程度高,且分子对接效果好。本研究推测藏麻黄挥发性成分对支气管炎的治疗作用机制可能是通过抑菌作用参与炎症反应,并通过抑制TNF、IL-17、Toll样受体等炎症与免疫信号通路中IL6、TNF、PTGS2、CXCL8的表达,从而起到治疗支气管炎的作用。研究结果为挖掘藏麻黄挥发性成分中治疗支气管炎靶标分子及其产品开发提供重要参考依据。