The effect of cigarette smoke on bleomycin-induced pulmonary fibrosis in hamsters

To investigate the effect of cigarette smoke on the development of bleomycin (BLM)-induced pulmonary fibrosis in hamsters, four experimental groups were studied: a control group (C), a cigarette smoke-inhaled group (T), a BLM-administered group (B), and a cigarette smoke-inhaled plus BLM-administered group (TB). Groups T and TB were exposed to sidestream smoke of cigarettes for 30 min/day, 5 days/wk. Groups B and TB were administered 0.5 mg BLM hydrochloride per 100 g body weight endotracheally once on day 30 (Day 0) after housing start. Quantitative morphometry of the lungs revealed that Group TB showed less lung fibrotic change compared with Group B, but based on qualitative observation, the fibrotic lesions of Group TB were intermingled with slight emphysematous changes. Neutrophils in bronchoalveolar lavage fluid were remarkably increased in both the groups, with a peak on Day 1, but the increase in Group TB lasted longer. Alveolar macrophages were increased in both smoking groups (T and TB) compared to the non-smoking groups (C and B). These results suggest that cigarette smoke reduces BLM-induced lung fibrotic changes; however, it simultaneously causes derangement of alveolar architecture. The persistence of increased neutrophils in the early phase after BLM accompanied by exposure to cigarette smoke may play an important role in the mechanism by which smoke ameliorates the effect of BLM.     

吸烟对大鼠肺动脉压和一氧化氮合酶的影响

目的 :探讨长期吸烟对大鼠肺动脉压及一氧化氮合酶的影响。方法 :SD雄性大鼠 40只 ,随机分为吸烟组和对照组 ,吸烟组暴露于点燃之烟卷 ,每日 6 h,于 9个月时检测吸烟组及对照组大鼠的肺动脉平均压 （m PAP）、血清一氧化氮 （NO）、肺动脉结构型一氧化氮合酶 （c NOS）和诱导型一氧化氮合酶 （i NOS）。结果 :吸烟组大鼠 m PAP明显高于对照组 ,血清 NO浓度与对照组相比明显减低 ,吸烟组肺细小动脉 c NOS平均吸光度值较对照组明显降低 ,吸烟组大鼠肺细小动脉 i NOS的平均吸光度值较对照组明显增高。结论 :烟雾可致肺动脉高压的形成 ,抑制肺细小动脉 c NOS表达、促进肺细小动脉 i NOS表达可能为其重要作用机制之一。     

Direct effect of cigarette smoke on human pulmonary artery tension

The effect of chronic cigarette smoke on pulmonary artery (PA) tension has been studied extensively; nevertheless, the direct effect of cigarette smoke is poorly understood. We investigated the direct effect of cigarette smoke extract (CSE) on PA tension in non-smokers, smokers, and COPD patients in vitro. PA samples from 35 patients who underwent lung resection were examined by measuring isometric tension in response to increasing serotonin concentrations. CSE dose dependently inhibited the response to serotonin in smokers and COPD patients, and to a lesser extent in non-smokers. CSE-induced relaxation was similarly inhibited by the nonspecific nitric oxide synthase (NOS) inhibitor l-NOARG and the specific inducible NOS (iNOS) inhibitor l-NIL, mainly in non-smokers and smokers, and to a lesser extent in COPD patients. Immunostaining of iNOS in PA samples was greater for smokers and COPD patients compared with non-smokers, which explains the lesser effect of CSE on PA tension in non-smokers. Moreover, CSE induced the release of nitrite via iNOS in human PA smooth muscle cells. In conclusion, CSE inhibition of serotonin-induced PA contraction was mediated mainly by iNOS in non-smokers, smokers, and COPD patients, but in different ways, which may be explained by differential iNOS expression in the PA of these patients.     

The additive effect of ethanol and extract of cigarette smoke on rabbit esophagus epithelium

Aim:  The combination of alcohol and smoking takes a place in the epidemiology and pathogenesis of gastroesophageal reflux disease and squamous cancers of the esophagus. Therefore, a study was designed to assess the impact of these agents alone or in combination on the structure and function of squamous epithelium of rabbit esophagus.
Methods:  Rabbit esophageal epithelium was mounted in Ussing Chambers, exposed luminally for ethanol (1–10%), extract of cigarette smoke (EOCS) and combinations or sequential application of these agents. An in-vivo model was also used to mimic conditions more representative of human alcohol consumption.
Results:  Ethanol (1–10%) dose dependently decreased tissue resistance. Extract of cigarette smoke caused a reduction on transepithelial potential difference (PD), short circuit current. Combinations of EOCS, ethanol (5–10% EtOH and EOCS 1–2) showed a more pronounced decrease than agents alone, mainly the result of EOCS. In vivo studies showed that EOCS administration dropped PD dose dependently. In-vivo 10% EtOH, EOCS-2 dropped PD (55%) similar to in-vitro 5% EtOH, EOCS-1. The effect was clearly additive; boluses of 10% ethanol (36%) and EOCS-2 (17%) decreased PD and combination of agents resulted in a 55% drop on PD which is a very similar decrease compared to the sum of the separate effects of agents (53%).
Conclusion:  Ethanol affected the barrier and cigarette smoke altered ion transport on rabbit esophageal epithelium under conditions reflecting human consumption. Results were consistent with in vivo and in vitro conditions except higher concentrations were needed in vivo . When applied, these agents showed an additive effect. Ethanol predisposed the tissue to the effect of EOCS.     

吸烟对支气管哮喘大鼠气道转化生长因子β1 mRNA和Ⅲ型胶原表达的影响

目的 探讨吸烟对支气管哮喘(简称哮喘)大鼠气道壁厚度及转化生长因子β1 mRNA(TGF-β1 mRNA)和Ⅲ型胶原表达的影响及作用机制.方法 健康雄性Wistar大鼠30只,按随机数字表法分为对照组、哮喘组和吸烟组,每组10只.用卵白蛋白致敏并吸入激发制备哮喘模型.吸烟组定量吸入香烟烟雾.采用逆转录-聚合酶链反应(RT-PCR)法测量TGF-β1 mRNA和免疫组化法测量Ⅲ型胶原表达.采用SPSS 11.0软件,所有数据以-x±s表示,组间比较采用单因素方差分析,组间差异比较采用LSD方差分析法,采用Pearson相关分析.结果 (1)吸烟组TGF-β1 mRNA、Ⅲ型胶原表达的吸光度(A)值分别为0.42±0.04、25.8±2.3,哮喘组分别为0.39±0.04、22.9±3.1,对照组分别为0.26±0.04、16.3±2.3,3组间比较差异有统计学意义(F值分别为55.97,35.61,P均＜0.05);(2)Pearson相关分析结果表明TGF-β1 mRNA与Ⅲ型胶原的表达呈正相关(r=0.71,P＜0.05);(3)气道壁厚度吸烟组为(23.3±2.4)μm2/μm,哮喘组为(20.1±2.9)μm2/μm,对照组为(11.6±2.4)μm2/μm,3组间比较差异有统计学意义(F=53.68,P＜0.05).结论 吸烟通过促进哮喘大鼠气道TGF-β1 mRNA的过度表达,增加气道Ⅲ型胶原表达,加重气道重塑的发生.     

The facilitating effect of cigarette smoke on the colonization of instilled bacteria into the tracheal lumen in rats and the improving influence of supplementary vitamin E on this process

OBJECTIVE: The aim of the present study was to investigate the direct influence of cigarette smoke on the bacterial colonization of the lower respiratory tract and the effect of supplementary vitamin E on the colonization of instilled bacteria into the trachea of rats that do not have the chronic airway pathology associated with smoking. METHODOLOGY: Thirty male Wistar albino rats, weighing approximately 250 g, were used as experimental animals. A 0.1 mL bacterial suspension containing six bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia, Proteus mirabilis, Haemophilus influenza, Peptostreptococci spp.), isolated previously from pharynx of rats, were instilled into the trachea of three groups of rat (10 control, 10 cigarette smoke-treated and 10 cigarette smoke- and vitamin E-supplemented rats). The smoke-treated rats were exposed to cigarette smoke for 3 days prior to and after intratracheal instillation. The third group of rats were given vitamin E supplements (100 mg/kg per day). Tracheobronchial lavage samples of all rats were quantitatively cultured after 3 days from the instillation. RESULTS: The colony numbers of isolated bacteria were significantly higher in cigarette smoke-treated rats than in the control group and in the smoke- and vitamin E-supplemented rats (P < 0.05). Only S. aureus and S. epidermidis were isolated from vitamin E-supplemented rats, while instilled all six bacterial species were isolated from the other two groups. CONCLUSIONS: It is concluded that smoking impairs the elimination of bacteria or facilitates colonization of bacteria in the lower respiratory tract of rats. Supplementary treatment with vitamin E reduces the effect of cigarette smoke; however, some bacteria may be resistant to this action of vitamin E.     

The effect of black coral extraction on acute lung inflammation induced by cigarette smoke in mice

Short-term exposure to cigarette smoke (CS) introduces an abundance of free radicals into the lungs, causing oxidative stress and inflammation. CS is an important risk factor related to the pathogenesis of several pulmonary diseases, especially chronic obstructive pulmonary disease. Black coral (BC) is a marine biomaterial commonly used for cigarette holders in southeast China. The purpose of the present study was to evaluate the in vivo bioactivity of BC extract (BCE). Groups of mice (male Kunming) were subjected to ultrasonic atomizing inhalation of BCE (0.3, 1.5, and 3 mg/mL) before being exposed to CS (10 cigarettes per day for 4 days). The control group and the CS group were administered normal saline rather than BCE prior to CS exposure. Superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) levels were measured in lung homogenates. Histologic and morphologic studies of the right upper lung were performed. SOD activity increased 1.32 times in the CS+BCE (3 mg/mL) group (P < .001) compared with the CS group. The MDA content increased 4% (P < .001) in the CS+BCE (3 mg/mL) group compared with the control group. MPO was reduced 40% in the CS+BCE (3 mg/mL) group compared with the CS group (P < .001). Histologic analysis revealed decreased inflammation in the BCE group compared with the CS group. These results suggest that BCE has antioxidant and anti-inflammatory activity in vivo. BCE may protect against lung injury in smokers.     

Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters

Cigarette smokers had an increased number of alveolar macrophages (AM) that had temporally related increases in oxidative metabolism in vitro compared with that in nonsmokers. The AM from young asymptomatic human cigarette smokers had a selective increase in superoxide anion (O2) release compared with those from nonsmokers. The AM from older smokers had a more intense, generalized enhancement of oxidative metabolism. Smoking hamsters had similar patterns of lung phagocyte recruitment and increased macrophage oxidative metabolism. The accumulation of AM within the alveolar ducts in smoking hamsters was strikingly similar to that seen in human smokers. The temporal patterns of smoke-induced changes in oxidative metabolism by AM from hamsters and humans were the same. Filtration of particulate constituents from cigarette smoke completely abrogated the distal airway inflammation and the metabolic alterations observed in smoking hamsters.     

Differential in vivo effects of whole cigarette smoke exposure versus cigarette smoke extract on mouse ciliated tracheal epithelium

In this study the authors compared the affect of vapor phase cigarette smoke (CS) versus cigarette smoke extract (CSE) on the lungs and upper airway of C57BL/6 mice. The authors found that CSE treatment significantly increased neutrophil influx (P < .001), baseline ciliary beat frequency (CBF) (P < .05), and protein kinase C activity compared to CS and controls. Isoproterenol increased CBF with CS exposure, but decreased CBF with CSE (P < .01). Isoproterenol increased protein kinase A (PKA) activity in all groups except CSE. CSE exposure induced inflammatory cell bronchiolitis. These data indicate that CSE exposure has differential effects on the lungs and tracheal epithelium compared to CS exposure.     

The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer

INTRODUCTION: Women who smoke have a higher rate of fatal breast cancer than nonsmoking women. An association between smoking and pulmonary metastases from breast cancer has been suggested by epidemiologic studies. STUDY OBJECTIVES: To examine the relationship between exposure to cigarette smoke and pulmonary metastasis in a murine model of metastatic mammary cancer. STUDY DESIGN: Prospective, randomized study. SETTING: Animal research laboratory. Experimental subjects: Female sexually mature BALB/cAnN mice. INTERVENTIONS: Mice were randomly divided into experimental and control groups. Experimental animals were exposed to cigarette smoke in specialized exposure chambers, at concentrations chosen to approximate active cigarette smoking. Control animals were exposed to filtered air. One week after the initiation of exposures, mouse mammary tumor cells (tumor cell line 4526) were injected into the tail veins of experimental animals at one of three concentrations (50,000, 100,000, or 150,000 cells per 100 micro L). Three weeks later, the mice were killed, and pulmonary metastases were counted and measured. RESULTS: The mean metastatic burden in the lungs was consistently greater for smoke-exposed animals at each concentration of cells injected (at 50,000 cells per 100 micro L, 9.8 vs 4.8 micro m(3), respectively [p < 0.01]; at 100,000 cells per 100 micro L, 34.5 vs 17.4 micro m(3), respectively [p < 0.10]; and at 150,000 cells per 100 micro L, 54.0 vs 31.5 micro m(3), respectively [p < 0.05]). This was largely attributable to a significant increase in the number of metastatic nodules per animal (at 50,000 cells per 100 micro L, 8.7 vs 4.8, respectively [p < 0.001]; at 100,000 cells per 100 micro L, 24.3 vs 14.0, respectively [p > 0.10]; and at 150,000 cells per 100 micro L, 42.0 vs 20.1, respectively [p < 0.02]) rather than to a change in nodule size. CONCLUSIONS: Cigarette smoke exposure is associated with an increase in the total pulmonary metastatic burden in this murine model of metastatic mammary cell cancer. This study provides experimental support for an adverse effect of smoking on the metastatic process and suggests a possible mechanism for smokers' increased breast cancer mortality.     

The effects of environmental tobacco smoke exposure before starting to smoke on cigarette quitting therapies

We aimed to determine the effects of environmental tobacco smoke (ETS) exposure before starting to smoke on cigarette quitting therapies and to determine source environment/individuals for ETS exposure. 230 individuals were contacted. We investigated person/s with ETS exposure before starting to smoke, places/duration of exposure, sources of exposure, therapy methods/durations recommended. Training seminar was also assumed as a therapy method. Those who were administered nicotine replacement and/or bupropion for a minimum of one week, 169 patients who only attended the training programme were evaluated. 68 patients who stopped smoking defined as controls, 101 patients who did not were defined as cases. There was no difference between case and control groups in terms of ages at initiation of smoking, ages at initiation of regular smoking, number of cigarettes per-day, total package-year and nicotine dependence score. 218 patients were found to have ETS exposure before starting to smoke. The highest ETS exposure was determined to be indoors (85.7%) and of paternal origin (77.2%). The rates of cigarette smoke exposure of maternal origin were 32.7% in cases, 25.4% in controls (p= 0.009 OR= 2.8). The mother being a smoker was found to increase the risk of not being able to stop smoking by 2.8 times. The number of people causing ETS exposure was higher in cases compared to controls (p= 0.044). ETS exposure have negative effects on the outcomes of cigarette quitting therapies. Indoor ETS exposure is the leading source of exposure. Therefore, indoor ETS exposure should be prevented, mothers should be trained concerning this matter.     

Inhibitory effect of gas phase cigarette smoke on breathing: role of hydroxyl radical

Inhaling cigarette smoke evokes immediate bradypnea in rats, resulting from stimulation of vagal bronchopulmonary C-fiber afferents by smoke constituent(s) other than nicotine. To determine the contribution of the gas phase of smoke to this irritant effect, the acute respiratory responses to both cigarette smoke and gas phase smoke were studied and compared in anesthetized Sprague-Dawley rats; smoke (6 ml, 50%) was generated by a machine from low-nicotine research cigarettes and the gas phase was obtained by passing the smoke through a glass-fiber Cambridge filter. Inhalation of gas phase smoke alone evoked a transient inhibitory effect on breathing, prolonging expiratory time (Te) to a peak of 159 +/- 6% of the base line; this response was very similar to that triggered by inhaling the unfiltered smoke (Te = 177 +/- 12%). The bradypnea started within 1-4 breaths after the onset of smoke inhalation, lasted for 3-5 breaths and was completely abolished by vagotomy. This inhibitory effect of gas phase smoke on breathing was also largely prevented after a pretreatment with either intravenous infusion or aerosol inhalation of a hydroxyl radical scavenger, dimethylthiourea. These results suggest that the gas phase is primarily responsible for eliciting the reflexogenic bradypneic response to cigarette smoke in anesthetized rats and that hydroxyl radicals released endogenously in the lungs may be involved.     

The effect of cholinergic blockade on the growth hormone response to galanin in humans

The effect of cholinergic blockade with pirenzepine or atropine on growth hormone (GH) release after galanin administration was investigated in five normal male subjects. The mean peak GH response to an infusion of galanin (40 pmol/kg/min for 40 minutes) was significantly reduced from 17.2 mU/L to 2.9 mU/L (P less than .001) with prior administration of pirenzepine (30 mg IV). When galanin was infused at a higher dose (80 pmol/kg/min), this suppression of release by pirenzepine was partially overcome, with GH rising to a mean peak response of 8.0 mU/L (P less than .05). Repeated administration of atropine (two bolus doses of 0.6 mg IV) also failed to abolish the GH response to this higher dose of galanin in two subjects. It has been proposed that cholinergic pathways control GH release via somatostatin, and this study suggests that galanin may also act by modulating hypothalamic somatostatinergic tone either directly or by facilitating cholinergic transmission.