BACKGROUND & AIMS: :To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV(1)/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV(1)/FVC, and girls with asthma had larger decreases in FEV(1)/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV(1), MMEF, and FEV(1)/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.

背景与目标： ：为了调查子宫内孕产妇吸烟和环境烟草烟雾（ETS）暴露对肺功能的影响是否因性别或哮喘状况而异，我们检查了儿童健康研究中5,263名参与者的病史和烟草烟雾暴露数据。在研究入组时，每个受试者的父母或监护人填写了一份调查表，并以最大的强制呼气流量对肺功能进行了肺活量测定。为了评估孕妇吸烟和ETS暴露对子宫功能的子宫内影响，我们使用了回归样条，该样条解释了肺功能，身高和年龄之间的非线性关系。子宫内母体吸烟与哮喘患儿的肺功能缺陷独立相关。有子宫内孕产妇吸烟史的男孩和女孩显示最大呼气中期流量不足（MMEF）和FEV（1）/ FVC比值降低。与没有哮喘的儿童相比，患有哮喘的男孩在子宫内暴露的FVC，MMEF和FEV（1）/ FVC的赤字明显更大，而患有哮喘的女孩FEV（1）/ FVC的跌幅更大。 ETS暴露的影响因儿童的性别和哮喘状况而异。哮喘患儿和非哮喘患儿当前与ETS暴露相关的血流不足，但仅在哮喘患儿中才有显着性。过去的ETS暴露与哮喘男孩中FEV（1），MMEF和FEV（1）/ FVC降低有关。相比之下，过去的ETS暴露与没有哮喘的女孩的血流量降低相关。总之，子宫内孕妇吸烟和ETS暴露均与持续的肺功能缺陷有关。子宫内暴露对哮喘患儿的影响最大。

BACKGROUND & AIMS: :The Electrically Heated Cigarette Smoking System Series K (EHCSS) produces smoke through the controlled electrical heating of tobacco. Evaluation of the EHCSS was accomplished by comparison with commercial and reference cigarettes, using International Organization for Standardization (ISO) and alternative puffing regimens based on nicotine exposures measured in a short-term clinical study. Using the alternative puffing regimen and compared with conventional cigarettes on a per cigarette basis, the EHCSS had 50-60% reductions in tar and nicotine; at least 90% reductions in carbon monoxide, nitrogen oxides, 1,3-butadiene, isoprene, acrylonitrile, polyaromatic hydrocarbons, hydrogen cyanide, aromatic amines, tobacco specific nitrosamines, and phenol; and least a 40% reduction in 2-nitropropane. Other important smoke constituents in EHCSS smoke were reduced as well. The in vitro studies showed similar large reductions in biological activity. Ames mutagenicity of total particulate matter (TPM) from the EHCSS was reduced by 70-90%; cytotoxicity of the TPM was reduced by approximately 82% and 65% for the gas-vapor phase. In vivo testing under ISO smoking conditions in the mouse skin painting assay demonstrated later dermal tumor onset, lower dermal tumor incidence, reduced dermal tumor multiplicity, and a lower proportion of malignant dermal tumors in EHCSS smoke condensate-exposed mice. Thirty-five day and 90-day nose-only inhalation studies in rats showed reductions in pulmonary inflammation and other biological activity, including histopathological endpoints. We conclude that under the conditions of these in vitro and in vivo studies, the EHCSS demonstrated significantly lower biological activity compared to conventional cigarettes, and may suggest the potential for reductions in human smokers.

背景与目标： ：K系列电加热烟熏系统（EHCSS）通过控制烟草的电加热来产生烟雾。通过使用国际标准化组织（ISO）和基于短期临床研究中测得的尼古丁暴露量的替代抽吸方法，通过与商用和参考卷烟进行比较，对EHCSS进行评估。使用替代的抽吸方法，并与传统卷烟相比，每支卷烟EHCSS的焦油和尼古丁含量降低了50-60％； EHCSS降低了焦油和尼古丁含量。一氧化碳，氮氧化物，1,3-丁二烯，异戊二烯，丙烯腈，聚芳烃，氰化氢，芳族胺，烟草特定的亚硝胺和苯酚至少减少90％;以及至少减少40％的2-硝基丙烷。 EHCSS烟雾中的其他重要烟雾成分也减少了。体外研究显示出类似的生物活性大幅降低。 EHCSS产生的总颗粒物（TPM）的Ames致突变性降低了70-90％；对于气相而言，TPM的细胞毒性降低了约82％和65％。在ISO吸烟条件下进行的小鼠皮肤涂漆测定法中的体内测试表明，在暴露于EHCSS烟雾的冷凝水中的小鼠，其皮肤肿瘤发作较晚，皮肤肿瘤发病率较低，皮肤肿瘤多重性降低以及恶性皮肤肿瘤的比例较低。在大鼠中进行的35天和90天仅鼻吸气研究表明，肺部炎症和其他生物学活性（包括组织病理学终点）降低了。我们得出的结论是，在这些体外和体内研究的条件下，与传统香烟相比，EHCSS具有明显更低的生物活性，并且可能暗示了减少人类吸烟者的潜力。

BACKGROUND & AIMS: Among 740 patients with acute burns who were admitted to our burn center from 1972 through, 1975, thirty-six required upper airway access within the first 24 hours after burn for oral and facial burns or smoke inhalation. Nasotracheal intubation was initially used. Twelve survived; 11 were successfully extubated and one required a tracheostomy. If the patient had not sustained major smoke inhalation, extubation was usually possible without tracheostomy when edema subsided between one and six days after the burn. It is concluded that endotracheal intubation is a satisfactory method of gaining airway control in severe oral and facial burns and in smoke inhalation. The mortality associated with orofacial burns or smoke inhalation is related to the degree of lung damage, patients' s age, and the extent of the burn; it is not related to the method of upper airway control.

背景与目标： 在1972年至1975年进入我们烧伤中心的740例急性烧伤患者中，有36例需要在烧伤后的前24小时内进行口腔和面部烧伤或吸入烟气。最初使用鼻气管插管。十二个幸存下来；成功拔管11例，其中1例需要气管切开术。如果患者未持续大量吸入烟气，则在烧伤后1至6天浮肿消退时，通常无需气管造口术即可拔管。结论是气管插管是在严重的口腔和面部烧伤以及吸入烟气中获得气道控制的令人满意的方法。口腔烧伤或吸入烟尘的死亡率与肺部损伤程度，患者的年龄以及烧伤程度有关。与上呼吸道控制方法无关。

BACKGROUND & AIMS: :4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic compound of cigarette smoke that generates electrophilic intermediates capable of damaging DNA. Recently, we have shown that NNK can modulate mediator production by alveolar macrophages (AM) and bronchial and alveolar epithelial cells, suggesting that cigarette smoke can alter lung immune response. Thus, we investigated the effect of NNK and cigarette smoke extract (CSE) on AM capacity to eliminate tumoral cells. Rat AM cell line, NR8383, was treated with NNK (500 microM) or CSE (3%) and stimulated with lipopolysaccharide (10 ng/ml). The release of cytotoxic mediators, tumor necrosis factor (TNF) and reactive oxygen species (ROS), was measured in cell-free supernatants using ELISA and superoxide anion production. TNF- and ROS-dependent cytotoxicity were studied using a (51)Chromium-release assay and WEHI-164 and P-815 cell lines. Treatment of AM with NNK and CSE for 18 h significantly inhibited AM TNF release. CSE exposure resulted in a significant increase of ROS production, whereas NNK did not. TNF-dependent cytotoxic activity of NR8383 and freshly isolated rat AM was significantly inhibited after treatment with NNK and CSE. Interestingly, although ROS production was stimulated by CSE and not affected by NNK, CSE inhibited AM ROS-dependent cytotoxicity. These results suggest that NNK may be one of the cigarette smoke components responsible for the reduction of pulmonary cytotoxicity. Thus, NNK may have a double pro-carcinogenic effect by contributing to DNA adduct formation and inhibiting AM cytotoxicity against tumoral cells.

背景与目标： ：4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是香烟烟雾的致癌化合物，可产生能够破坏DNA的亲电子中间体。最近，我们已经显示NNK可以调节肺泡巨噬细胞（AM）以及支气管和肺泡上皮细胞的介体产生，这表明香烟烟雾可以改变肺部免疫反应。因此，我们研究了NNK和香烟烟雾提取物（CSE）对AM消除肿瘤细胞能力的影响。用NNK（500 microM）或CSE（3％）处理大鼠AM细胞系NR8383，并用脂多糖（10 ng / ml）刺激。使用ELISA和超氧阴离子产生法在无细胞上清液中测量细胞毒性介质，肿瘤坏死因子（TNF）和活性氧（ROS）的释放。使用（51）铬释放试验以及WEHI-164和P-815细胞系研究了TNF-依赖性和ROS依赖性细胞毒性。用NNK和CSE治疗AM 18小时可显着抑制AM TNF释放。 CSE暴露导致ROS产生显着增加，而NNK则没有。用NNK和CSE处理后，NR8383和新鲜分离的大鼠AM的TNF依赖性细胞毒性活性被显着抑制。有趣的是，尽管CSE刺激了ROS的产生，而不受NNK的影响，但CSE抑制了AM ROS依赖性的细胞毒性。这些结果表明，NNK可能是引起肺细胞毒性降低的香烟烟雾成分之一。因此，通过促进DNA加合物的形成并抑制AM对肿瘤细胞的细胞毒性，NNK可能具有双重致癌作用。

BACKGROUND & AIMS: :BACKGROUND: Indonesia has the second highest smoking prevalence among adult males in the world, and smoking prevalence is increasing among youths.OBJECTIVE: To evaluate the smoke-free policy (SFP), a flagship national tobacco control programme, by providing evidence on geographic distribution, socio-economic disparities and policy determinants of SFP adoption by district in Indonesia.METHODS: We employed spatial and quantitative methods to obtain data respectively on geographic distribution of SFP adoption, and on disparities and associations between national and provincial SFP regulations and SFP adoption by the districts.RESULTS: Twenty-one of 34 provinces, and 345 of 514 districts adopted SFP. We found significant geographic disparities: all districts outside of Papua were up to 6.3 times more likely to adopt the policy and to implement it for a period of up to 3 years longer in duration. We also found significant socio-economic disparities: urban districts, those that were wealthiest and those most educated were respectively 3.9, 9.1 and 2.8 times more likely to adopt the policy. Moreover, districts in provinces that had SFP regulation were 3.2 times more likely to adopt. Finally, the adoption rate in the period after the 2012 national regulation was up to 7.8 times higher than that before.CONCLUSION: In addition to geographic and socio-economic disparities, national and provincial regulations and policies were determinants of SFP adoption.

背景与目标： 背景：印度尼西亚是世界上成年男性中吸烟率第二高的国家，年轻人中吸烟率正在上升。目标：通过提供地理上的证据来评估国家无烟政策的旗舰性无烟政策（SFP）方法：我们采用空间和定量方法分别获得了有关SFP采伐地理分布的数据，以及国家和省级SFP法规与SFP采伐之间的差距和关联的数据结果：34个省中的21个省和514个区中的345个区采用了SFP。我们发现了巨大的地理差异：巴布亚以外的所有地区采用该政策的可能性提高了6.3倍，并且实施该政策的时间最多延长了3年。我们还发现了巨大的社会经济差异：城市，最富有的地区和受教育程度最高的地区，采用该政策的可能性分别高3.9倍，9.1倍和2.8倍。此外，具有SFP法规的省份采用该法规的可能性要高3.2倍。最后，2012年国家法规实施后的采用率是之前的7.8倍。结论：除了地理和社会经济差异外，国家和省级法规政策也是SFP采纳的决定因素。

BACKGROUND & AIMS: :The genotoxic effects of 90-day nose-only exposures to smoke from new cigarettes, which heat but do not burn tobacco (New), or from reference cigarettes, which burn tobacco, were evaluated in Sprague-Dawley rats by examining the cytogenetic endpoints of sister-chromatid exchanges (SCE), chromosome aberrations, and micronuclei in bone-marrow cells. The concentrations of wet total particulate matter (WTPM) and carbon monoxide in the smoke from both cigarette types were similar. The mainstream smoke from both New and reference cigarettes was adjusted to WTPM concentrations of approx. 200 and 400 micrograms/l for low and high smoke exposure. Rats were exposed to smoke 1 h per day, 5 days per week for 13 consecutive weeks. Inhalation of smoke by the exposed animals was confirmed by analysis of blood carboxyhemoglobin and plasma nicotine. Examination of bone-marrow cells following the final day of exposure showed that smoke from neither the New nor reference cigarette induced a positive response in the SCE, chromosome aberration, or micronucleus assays in rats.

背景与目标： ：在Sprague-Dawley大鼠中，通过检查细胞遗传学终点，评估了仅90天鼻饲暴露于加热但不燃烧烟草的新香烟（新）或参考香烟燃烧的烟的遗传毒性作用。染色单体交换（SCE），染色体畸变和骨髓细胞中的微核的变化。两种香烟的烟雾中的湿总颗粒物（WTPM）和一氧化碳的浓度相似。将新卷烟和参考卷烟的主流烟气调节至WTPM浓度约为。 200和400微克/升，适用于低烟量和高烟量。将大鼠每天1小时，每周5天，每天连续13周暴露于烟雾中。通过分析血液中的羧基血红蛋白和血浆尼古丁来确认暴露的动物吸入烟气。暴露的最后一天后对骨髓细胞的检查表明，新香烟和参比香烟中的烟雾均未在大鼠的SCE，染色体畸变或微核试验中诱导阳性反应。

BACKGROUND & AIMS: :As smoke-free car policy is a frontier domain for tobacco control, attitudes to smoke-free private car laws are briefly reviewed. Medline and Google Scholar searches for the period up to mid-November 2008, from English language sources, were undertaken. Studies were included that contained data from national and subnational populations (eg, in states and provinces), but not for smaller administrative units, eg, cities or councils. Jurisdiction, sample size and survey questions were assessed. One reviewer conducted the data extraction and both authors conducted assessments. A total of 15 relevant studies (from 1988) were identified, set in North America, the UK and Australasia. The available data indicates that, for the jurisdictions with data, there is majority public support for laws requiring cars that contain children to be smoke free. There appears to be an increase over time in this support. In five surveys in 2005 or since (in California, New Zealand and Australia), the support from smokers was 77% or more. The high levels of public (and smoker) support for smoke-free car laws found in the studies to date suggest that this can be a relatively non-controversial tobacco control intervention. Survey series on attitudes to such laws are needed, and surveys in jurisdictions where the issue has not been investigated to date.

背景与目标： ：由于无烟汽车政策是烟草控制的前沿领域，因此简要回顾了对无烟私家车法律的态度。 Medline和Google Scholar进行了英语来源的搜索，搜索截止到2008年11月中旬。纳入的研究包含来自国家和地方以下人口的数据（例如，州和省），但不适用于较小的行政单位（例如，城市或议会）。评估了司法管辖区，样本量和调查问题。一位审稿人进行了数据提取，两位作者进行了评估。共确定了15项相关研究（自1988年起），分别在北美，英国和大洋洲进行。现有数据表明，对于有数据的司法管辖区，大多数公众支持法律要求载有儿童的汽车禁止吸烟。随着时间的推移，这种支持似乎有所增加。在2005年或此后的五项调查中（在加利福尼亚，新西兰和澳大利亚），吸烟者的支持率为77％或更多。迄今为止，在研究中发现，公众（和吸烟者）对无烟汽车法律的高度支持表明这可能是相对无争议的烟草控制干预措施。需要对此类法律的态度进行一系列调查，并在迄今尚未对该问题进行调查的辖区中进行调查。

BACKGROUND & AIMS: PURPOSE:Smokers have increased denture stomatitis caused primarily by Candida albicans. The primary aim of this study was to demonstrate the impact of a wide range of nicotine and cigarette smoke condensate (CSC) concentrations on biofilm formation and metabolic activity of C. albicans on acrylic denture material. MATERIALS AND METHODS:C. albicans (ATCC strain 10231) was used. Standardized denture acrylic (PMMA) specimens (total of 135 specimens) were incubated with C. albicans and exposed to nicotine and CSC at different concentrations (0, 0.25, 0.5, 1, 2, 4, 8, 16, and 32 mg/ml) and (0, 0.25, 0.5, 1, 2, and 4 mg/ml), respectively. For each experiment, 3 samples per nicotine and CSC concentration and a total of 45 specimens (27 specimens for the nicotine and 18 specimens for the CSC-treated samples) were used and were selected randomly for each group. The control group consisted of 0 mg/ml of nicotine or CSC. The viability of C. albicans was measured using spiral plating on blood agar plates. The effect of nicotine and CSC concentrations on planktonic cells was were measured using a microplate reader. Metabolic activity of 24-hour-old established C. albicans biofilm exposed to nicotine and CSC for 24 hours in microtiter plates was determined using a 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-carboxanilide (XTT) reduction assay. RESULTS:The viability of C. albicans increased concomitant with increasing concentrations of CSC and nicotine, particularly at 0.5 and 2 mg/ml, respectively. Concentrations of CSC and nicotine above this resulted in an inhibitory effect on C. albicans viability. CSC and nicotine at 4 and 16 mg/ml, respectively, increased C. albicans biofilm metabolic activity. CONCLUSION:Nicotine and CSC up to certain concentrations caused increases in biofilm formation, metabolic activity, viability, and planktonic cell absorbance of C. albicans. This in vitro study demonstrates the effectiveness of tobacco on promoting the growth of C. albicans and suggests their potential contributing factor in C. albicans biofilm related infections in smokers.

背景与目标： 目的：吸烟者增加的假牙口腔炎主要由白色念珠菌引起。这项研究的主要目的是证明各种尼古丁和香烟烟雾冷凝物（CSC）的浓度对丙烯酸假牙材料上白念珠菌生物膜形成和代谢活性的影响。
材料与方法：C．使用白色念珠菌（ATCC菌株10231）。将标准义齿丙烯酸（PMMA）标本（共135个标本）与白色念珠菌一起孵育，并以不同浓度（0、0.25、0.5、1、2、4、8、16和32 mg / ml的尼古丁和CSC暴露） ）和（0、0.25、0.5、1、2和4 mg / ml）。对于每个实验，每个尼古丁和CSC浓度使用3个样品，共使用45个样本（尼古丁为27个样本，CSC处理的样本为18个样本），并随机选择每组。对照组由0 mg / ml尼古丁或CSC组成。使用螺旋琼脂平板在血琼脂平板上测量白色念珠菌的生存力。使用酶标仪测量尼古丁和CSC浓度对浮游细胞的影响。使用2,3-双（2-甲氧基-4-硝基-5-硝基苯基）-2H-四唑鎓测定在微量滴定板中暴露于尼古丁和CSC中24小时的24小时建立的白色念珠菌生物膜的代谢活性-甲酰苯胺（XTT）还原测定。
结果：白色念珠菌的生存能力随着CSC和烟碱浓度的增加而增加，尤其是分别在0.5和2 mg / ml时。高于此浓度的CSC和烟碱会导致对白色念珠菌生存能力的抑制作用。 CSC和尼古丁分别以4和16 mg / ml的浓度增加白色念珠菌的生物膜代谢活性。
结论：高达一定浓度的尼古丁和CSC导致白色念珠菌的生物膜形成，代谢活性，活力和浮游细胞吸收增加。这项体外研究证明了烟草在促进白色念珠菌生长方面的有效性，并表明了烟草在吸烟者中白色念珠菌生物膜相关感染的潜在影响因素。

BACKGROUND & AIMS: :Phosphatase activity of the major serine threonine phosphatase, protein phosphatase 2A (PP2A), is blunted in the airways of individuals with chronic obstructive pulmonary disease (COPD), which results in heightened inflammation and proteolytic responses. The objective of this study was to investigate how PP2A activity is modulated in COPD airways. PP2A activity and endogenous inhibitors of PP2A were investigated in animal and cell models of COPD. In primary human bronchial epithelial (HBE) cells isolated from smokers and donors with COPD, we observed enhanced expression of cancerous inhibitor of PP2A (CIP2A), an oncoprotein encoded by the KIAA1524 gene, compared with cells from nonsmokers. CIP2A expression was induced by chronic cigarette smoke exposure in mice that coincided with a reduction in PP2A activity, airspace enlargements, and loss of lung function, as determined by PP2A phosphatase activity, mean linear intercept analysis, and forced expiratory volume in 0.05 second/forced vital capacity. Modulating CIP2A expression in HBE cells by silencing RNA or chemically with erlotinib enhanced PP2A activity, reduced extracellular-signal-regulated kinase phosphorylation, and reduced the responses of matrix metalloproteinases 1 and 9 in HBE cells isolated from subjects with COPD. Enhanced epithelial growth factor receptor responses in cells from subjects with COPD were observed to modulate CIP2A expression levels. Our study indicates that chronic cigarette smoke induction of epithelial growth factor receptor signaling and CIP2A expression can impair PP2A responses that are associated with loss of lung function and enhancement of proteolytic responses. Augmenting PP2A activity by manipulating CIP2A expression may represent a feasible therapeutic approach to counter smoke-induced lung disease.

背景与目标： 慢性阻塞性肺疾病（COPD）个体的气道中主要丝氨酸苏氨酸磷酸酶2A（PP2A）的磷酸酶活性减弱，导致炎症和蛋白水解反应增强。这项研究的目的是调查如何在COPD气道中调节PP2A活性。在COPD的动物和细胞模型中研究了PP2A活性和PP2A的内源性抑制剂。在从患有COPD的吸烟者和供体中分离出的原代人支气管上皮（HBE）细胞中，我们观察到与不吸烟者相比，由KIAA1524基因编码的癌蛋白PP2A（CIP2A）的癌性抑制剂的表达有所提高。 CIP2A表达是由小鼠长期吸烟引起的，与PP2A活性降低，空域扩大和肺功能丧失相吻合（PP2A磷酸酶活性，平均线性截距分析和强制呼气量以0.05秒/强迫测定）肺活量。通过沉默RNA或化学作用与厄洛替尼调节HBE细胞中的CIP2A表达，可增强PP2A活性，减少细胞外信号调节的激酶磷酸化，并减少从患有COPD的受试者中分离的HBE细胞中基质金属蛋白酶1和9的反应。观察到来自患有COPD的受试者的细胞中增强的上皮生长因子受体应答调节了CIP2A表达水平。我们的研究表明，长期吸烟诱导上皮生长因子受体信号传导和CIP2A表达可削弱与肺功能丧失和蛋白水解反应增强相关的PP2A反应。通过控制CIP2A的表达来增强PP2A的活性可能是对抗烟尘诱发的肺部疾病的一种可行的治疗方法。

BACKGROUND & AIMS: :Cigarette smoke (CS) is the leading risk factor to develop COPD. Therefore, the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC) were investigated, using cells from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions. The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity. Although, COPD-derived ALI cultures preserved some features known from COPD patients, CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls. RNA sequencing analyses revealed the deregulation of marker genes for basal and secretory cells upon CS exposure. The comparison between gene signatures obtained from the in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) revealed a high degree of similarity between deregulated genes and pathways induced by CS. Taken together, whole cigarette smoke alters the differentiation of small airway basal cells in vitro. The established model showed a good translatability to the situation in vivo. Thus, the model can help to identify and test novel therapeutic approaches to restore the impaired epithelial repair mechanisms in COPD, which is still a high medical need.

背景与目标： ：香烟烟雾（CS）是发展COPD的主要危险因素。因此，使用来自三名健康供体和三名COPD患者的细胞，在ALI（气液界面）条件下培养，研究了整个CS对原代小气道上皮细胞（SAEC）分化的病理学影响。上皮生理学分析表明，CS损害了屏障形成并降低了纤毛搏动活性。尽管源自COPD的ALI培养物保留了COPD患者已知的某些特征，但与健康对照相比，来自患者的ALI培养物中CS诱导的作用相似。 RNA测序分析揭示了CS暴露后基底细胞和分泌细胞标记基因的失控。从体外模型（CS与空气）获得的基因特征与人类上皮刷（吸烟者与非吸烟者）的公开数据集之间的比较表明，失调基因与CS诱导的途径之间存在高度相似性。总体而言，香烟烟雾在体外会改变小气道基底细胞的分化。建立的模型对体内情况显示出良好的可翻译性。因此，该模型可以帮助鉴定和测试新颖的治疗方法以恢复COPD中受损的上皮修复机制，这仍然是高度医疗需求。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A survey of the nicotine, tar, and carbon monoxide (CO) levels in mainstream smoke from 21 brands of bidi cigarettes and five brands of traditional cigarettes was conducted using a variation of the Federal Trade Commission (FTC) standardized cigarette smoking machine method. The primary difference between this method and the FTC method was a reduction of the 60-s puff interval to 15 s. The shorter puff interval was required to prevent the bidi cigarettes from self-extinguishing and may represent a closer approximation to human usage. The goal of this study was to evaluate the smoke-delivery potential for tar, nicotine, and CO in mainstream smoke from bidi cigarettes compared with traditional domestic cigarettes smoked under identical conditions. Approximately half of the bidi brands examined were marketed as filtered varieties. Unlike traditional cigarettes, the filtered and unfiltered bidi brands yielded comparable smoke deliveries. Thus, a filtered bidi cigarette brand does not provide any harm-reduction benefit that might result from a reduction in levels of tar, nicotine, and CO compared with an unfiltered variety. Our findings indicate that bidi cigarettes can deliver high levels of tar (77.9+/-9.5 mg/bidi), nicotine (2.7+/-.4 mg/bidi), and CO (39.2+/-5.7 mg/bidi). In comparison, traditional cigarettes smoked using the bidi cigarette protocol have lower tar and CO yields, but have nicotine deliveries comparable with bidi cigarettes.

背景与目标： ：使用联邦贸易委员会（FTC）标准化吸烟机方法对21种比迪烟和5种传统烟的主流烟中尼古丁，焦油和一氧化碳（CO）含量进行了调查。此方法与FTC方法之间的主要区别是将60秒的抽吸间隔减少到15秒。需要较短的抽吸间隔以防止比迪烟自动熄灭，并且可能代表更接近人类的使用习惯。这项研究的目的是评估与在相同条件下吸烟的传统家用卷烟相比，比迪烟主流卷烟中焦油，尼古丁和一氧化碳的释放潜力。所调查的比迪烟品牌中大约有一半以过滤后的品种销售。与传统卷烟不同，经过过滤和未经过滤的比迪烟品牌产生的烟雾可比。因此，与未经过滤的比迪烟相比，经过过滤的比迪烟品牌不会提供任何减少焦油，尼古丁和一氧化碳含量的危害。我们的研究结果表明，比迪烟可以释放高含量的焦油（77.9 /-9.5毫克/比迪），尼古丁（2.7 /-.4毫克/比迪）和一氧化碳（39.2 /-5.7毫克/比迪）。相比之下，使用比迪烟方案吸烟的传统卷烟的焦油和一氧化碳产量较低，但尼古丁的释放量与比迪烟可比。

BACKGROUND & AIMS: :Exposure to particulate matter less than 2.5 microns from either ambient pollution (AMB-PM2.5) or secondhand smoke (SHS-PM2.5) have been associated with asthma worsening, but there is little information on effects and relative potency with concurrent exposures. We studied health effects of concurrent exposures to AMB-PM2.5 and SHS-PM2.5 over a 6-year period in schoolchildren with asthma. Regression calibration with instrumental variables (RCIV) was utilized to estimate effects of personal exposure to low-level SHS and AMB-PM2.5 on daily albuterol usage and urinary leukotriene E4 (uLTE4; a biomarker of asthma-related inflammation) using urine cotinine and concentrations from fixed and personal pollution monitors. Each IQR increase in SHS-PM2.5 exposure was associated with a 6.7% increase (95% CI: 1.0-12.8%) in uLTE4 on the same day and 9.4% increase (95% CI: -2.6 to 22.7%) in albuterol use the next day, when children were co-exposed to mean levels of AMB-PM2.5. The dose-response relationship between health outcomes and one pollutant was higher at lower levels of the other pollutant. For example, at lower levels of predicted SHS-PM2.5 exposure, increases in health outcomes per IQR increase in AMB-PM2.5 ranged between 2 and 5%, but were negligible at higher SHS-PM2.5 levels. Comparing at equivalent co-exposure levels, SHS-PM2.5 was 1.6 times more potent than AMB-PM2.5 for uLTE4 (95% CI: 1.1-2.3); estimates for albuterol usage were similar but less significant. Effects at mean co-exposure levels were closer [SHS to AMB-PM2.5 potency ratio = 1.2 (95% CI: 0.9-1.5) for uLTE4 and 1.2 (95% CI: 0.7-1.9) for albuterol usage]. In summary, concurrent exposure to relatively low levels of SHS and AMB-PM2.5 were associated with health outcomes in asthmatic schoolchildren. Dose responses varied with changes in the relative amounts of each pollutant; SHS-PM2.5 was observed to be more potent than AMB-PM2.5 when co-exposure levels were equivalent.

背景与目标： ：暴露于环境污染（AMB-PM2.5）或二手烟（SHS-PM2.5）小于2.5微米的颗粒物与哮喘恶化有关，但很少有关于同时暴露的影响和相对效力的信息。我们研究了哮喘学龄儿童在6年内同时接触AMB-PM2.5和SHS-PM2.5对健康的影响。利用工具变量（RCIV）进行回归校准，使用尿液可替宁和来自固定和个人污染监测仪的浓度。 IHS SHS-PM2.5暴露量每增加一次，则uLTE4在同一天增加6.7％（95％CI：1.0-12.8％），沙丁胺醇增加9.4％（95％CI：-2.6至22.7％）。第二天使用，当孩子被共同暴露于AMB-PM2.5的平均水平时。健康结果与一种污染物之间的剂量反应关系在另一种污染物的含量较低时较高。例如，在较低水平的预计SHS-PM2.5暴露水平下，AMB-PM2.5中每IQR增加的健康结果增加幅度为2％至5％，但在较高的SHS-PM2.5水平下可以忽略不计。在同等的共同暴露水平下，对于uLTE4（95％CI：1.1-2.3），SHS-PM2.5的效力是AMB-PM2.5的1.6倍；沙丁胺醇使用量的估算值相似，但意义不大。在平均共同暴露水平下的效果更接近[对于uLTE4，SHS与AMB-PM2.5效力比= 1.2（95％CI：0.9-1.5），对于沙丁胺醇使用，SHS与AMB-PM2.5的效力比为1.2（95％CI：0.7-1.9）]。总之，哮喘小学生同时暴露于相对较低水平的SHS和AMB-PM2.5与健康状况相关。剂量响应随每种污染物相对含量的变化而变化；当共同暴露水平相同时，观察到SHS-PM2.5比AMB-PM2.5更有效。

BACKGROUND & AIMS: INTRODUCTION:Environmental tobacco smoke (ETS) is a hazardous component of indoor air, and may increase the risk of respiratory diseases, atherosclerosis and otitis media in children. In this study, we explored the relationship between time inside the house, ETS exposure and urinary cotinine level, and also determined the association of time inside the house on asthma phenotypes when children exposed to ETS. METHODS:A total of 222 asthmatic children and 205 non-asthmatic controls were recruited in the Genetic and Biomarker study for Childhood Asthma (GBCA). Structured questionnaires and time-location pattern questionnaires were administered by face-to-face interview. Urinary cotinine was measured by liquid chromatography tandem mass spectrometry (LC/MS/MS). The level of household ETS exposure was assessed using the cotinine/creatinine ratio (CCR). RESULTS:In general, urinary cotinine and CCR were higher in subjects exposed to household ETS than those who never had ETS at home. A significant positive relationship was found between average time inside the house and urinary CCR in asthmatic children with current ETS at home (β=0.278, p=0.02). After adjustment for age and gender, average time inside the house was positively related to severe wheeze in asthmatic children with household ETS within 1 month (OR: 1.26, 95%: 1.02-1.64). CONCLUSIONS:Our study suggests that the major source of ETS exposure for children is due to longer period of exposures among children living with adult smokers at home. Home-smoking restrictions that effectively prevent children from being exposed to ETS would be worthwhile.

背景与目标： 简介：环境烟草烟雾（ETS）是室内空气中的有害成分，可能会增加儿童患呼吸道疾病，动脉粥样硬化和中耳炎的风险。在这项研究中，我们探讨了屋内时间，ETS暴露量与尿可替宁水平之间的关系，并确定了屋内时间与儿童暴露于ETS时哮喘表型的相关性。
方法：在儿童哮喘的遗传和生物标志物研究（GBCA）中，共招募了222名哮喘儿童和205名非哮喘控制者。通过面对面访谈来管理结构化问卷和时空模式问卷。尿可替宁通过液相色谱串联质谱法（LC / MS / MS）测定。使用可替宁/肌酐比值（CCR）评估家庭ETS暴露水平。
结果：一般而言，暴露于家庭ETS的受试者的尿中可替宁和CCR高于在家中从未接受过ETS的受试者。在目前在家中有ETS的哮喘儿童中，平均室内时间与尿液CCR之间存在显着的正相关（β= 0.278，p = 0.02）。在调整了年龄和性别之后，在1个月内有家庭ETS的哮喘儿童的室内平均时间与严重喘息呈正相关（OR：1.26，95％：1.02-1.64）。
结论：我们的研究表明，儿童ETS暴露的主要来源是由于在家中有成年吸烟者的儿童中暴露时间更长。有效防止儿童接触ETS的家庭吸烟限制将是值得的。

BACKGROUND & AIMS: BACKGROUND:It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium, plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. METHODS:The levels of IL-1 β, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells' apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. RESULTS:In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 β, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress. CONCLUSIONS:The above results collectively suggested that ALT suppressed CSE-induced inflammation, apoptosis and oxidative stress by modulating the NF-ĸB and Nrf2/ HO-1 axis.

背景与目标： 背景：众所周知，气道重塑和炎症是慢性阻塞性肺疾病（COPD）的特征。此外，香烟烟雾提取物（CSE）促进了COPD的炎症，细胞凋亡和氧化应激。并且，有证据表明，从菊粉中分离出的倍半萜内酯丙内酯（ALT）在炎症，细胞凋亡和氧化应激中起着不利的作用。但是，很少有研究调查ALT治疗对COPD病理过程的功能和机制。
方法：采用ELISA法检测IL-1β，TNF-α，IL-6和IFN-γ的水平。通过细胞死亡检测PLUS酶联免疫吸附测定法和caspase-Glo 3/7测定法分别检测细胞的凋亡和caspase-3活性。使用MDA和SOD分析试剂盒测定丙二醛（MDA）和超氧化物歧化酶（SOD）的含量。通过DCFH-DA测定法测量活性氧（ROS）的产生。通过蛋白质印迹法测定蛋白质表达。
结果：在本研究中，我们旨在观察ALT对人支气管上皮Beas-2B和NHBE细胞炎症，凋亡和氧化应激的保护作用。我们的结果表明，不同剂量的CSE暴露诱导Beas-2B和NHBE细胞炎性细胞因子IL-1β，TNF-α，IL-6和IFN-γ的表达，细胞凋亡，caspase-3活性和介导的氧化应激标记MDA， ROS和SOD水平，而ALT治疗则抵消了CSE的影响。进一步的研究表明，ALT减弱了NF-κB途径的激活。 ALT还通过促进Nrf2核聚集和下游HO-1蛋白表达来激活Nrf2 / HO-1信号途径。 HO-1抑制剂锡原卟啉IX（SnPP IX）逆转了ALT对Beas-2B和NHBE细胞炎症，细胞凋亡和氧化应激的影响。
结论：以上结果共同提示，ALT通过调节NF-ĸB和Nrf2 / HO-1轴来抑制CSE诱导的炎症，细胞凋亡和氧化应激。