Environmental tobacco smoke: Association with cardiovascular function at rest and during stress

Chronic exposure to environ mental tobacco smoke (ETS) contributes to cardiovascular disease morbidity and mortality, and ETS alters cardiovascular performance during exercise stress. However, no study has examined whether those with ETS exposure have altered cardiovascular functioning during psychological stress, relative to those with no substantial ETS exposure. Seventy-eight healthy, nonsmoking adult men with either high levels of current ETS exposure at home and work or no current or significant lifetime ETS exposure were tested in a stress reactivity protocol. Blood pressure and heart rate were monitored during rest and during two psychological stressors. Those with high ETS exposure had significantly elevated heart rate and blood pressure at baseline, relative to those with no exposure. The groups did not differ on their cardiovascular stress responses. These data suggest that chronic ETS exposure is associated with altered cardiovascular functioning at rest, but not during stress. Results are discussed with regard to the role of ETS on the development of heart disease among nonsmokers.     

The effects of passive inhalation of cigarette smoke on exercise performance

Summary The purpose of this investigation was to evaluate the effect of passive smoke inhalation on submaximal and maximal exercise performance. Eight female subjects ran on a motor driven treadmill for 20 min at 70% followed by an incremental change in grade until maximal work capacity was obtained. Each subject completed the exercise trial with and without the presence of residual cigarette smoke. Compared to the smokeless trials, the passive inhalation of smoke significantly reduced maximal oxygen uptake by 0.25 1·min⁻¹ and time to exhaustion by 2.1 min. The presence of sidestream smoke also elevated maximal R value (1.01 vs 0.93), maximal blood lactate (6.8 vs 5.5 mM), and ratings of perceived exertion (17.4 vs 16.5 units). Passive inhalation of smoke during submaximal exercise significantly elevated the CO₂ output (1.68 vs 1.58 l·min⁻¹),R values (0.91 vs 0.86), heart rate (178 vs 172 bts·min⁻¹) and rating of perceived exertion (13.8 vs 11.8 units). These findings suggest that passive inhalation of sidestream smoke adversely affects exercise performance.     

Volatile N-nitrosamines in mainstream cigarette smoke: occurrence and formation

Summary Analytical data is presented for the occurrence of the three major volatile N-nitrosamines in cigarette tobacco and mainstream smoke, namely N-nitrosodimethylamine (NDMA), N-nitrosoethylmethylamine (NEMA) and N-nitrosopyrrolidine (NPYR) as well as for the occurrence of the corresponding precursor amines and non-volatile N-nitrosamino acids in tobacco. Experimental studies using the C20 reference cigarette show that NPYR present in mainstream smoke results from direct transfer of preformed NPYR (ca. 1.5%), decarboxylation of N-nitrosoproline in tobacco (ca. 10%), pyrolytic nitrosation of pyrrolidine in tobacco (ca. 37%) and concerted decarboxylation/nitrosation of proline (ca. 52%) during tobacco pyrolysis.Abbreviations DMA dimethylamine - EMA ethylmethylamine - iNEP isonipecotic acid - NDEA N-nitrosodiethylamine - NDMA N-nitrosodimethylamine - NDMMOR N-nitroso-2,2-dimethylmorpholine - NEMA N-nitrosoethylmethylamine - NEP N-nitrosonipecotic acid - NMPA 4-(N-nitrosomethylamino)butyric acid - NMPA 3-(N-nitrosomethylamino)propionic acid - NPIC N-nitrosopipecolic acid - NPIP N-nitrosopiperidine - NPRO N-nitrosoproline - NPYR N-nitrosopyrrolidine - NSAR N-nitrososarcosine - PIC pipecolic acid - PIP piperidine - PYR pyrrolidine - TEA thermal energy analyser - TSNA tobacco-specific N-nitrosamines     

The effect of active and passive maternal smoking before and during pregnancy on neonatal weight at birth

IntroductionSmoking during pregnancy is a risk factor for adverse pregnancy outcomes. Data on the correlation between passive maternal smoking and pregnancy outcomes remain limited. We investigated the effect of active smoking and environmental tobacco smoke (ETS) during pregnancy on neonatal birthweight, including the risk for low birthweight (LBW).Material and methodsThe study was conducted between 2010 and 2012. A group of 8625 women were surveyed during postpartum hospitalization. Outcome measures included mean birthweight of newborns. Additionally, odds ratios with confidence intervals were calculated to investigate the risk for LBW in active and passive smoking groups of mothers.ResultsLower birthweight (46 g – 307 g; p < 0.05) and a higher risk for LBW (OR = 1.35, 95% CI: 1.05–1.75; p < 0.05) were observed in all infants born to smoking mothers. A negative effect of ETS in pregnancy on the reduction of mean birthweight was also found. Additionally, we analyzed the cumulative effect of active and passive smoking on neonatal birthweight. A statistically significant reduction in neonatal weight at birth was found in a group of women who smoked actively and passively during pregnancy (130 g; p < 0.05).ConclusionsSmoking is associated with decreased birthweight and in a group of active smoking mothers increased risk for LBW. This effect is dose-dependent and is also present in a group of women who smoked before pregnancy. There is also a cumulative effect of active smoking and ETS causing decreased neonatal birthweight and increased risk for low birthweight.     

Evaluation method for the cytotoxicity of cigarette smoke by in vitro whole smoke exposure

An in vitro whole smoke (WS) exposure method was established to evaluate the toxicological effects of fresh cigarette smoke using the VITROCELL^® system associated with the neutral red uptake (NRU) cytotoxicity assay. The VITROCELL^® system is a newly representative culture and exposure system for in vitro studies of gases or complex mixtures. The impacts of two factors on cytotoxicity measurements of cigarette smoke were investigated using this WS exposure system. The factors include synthetic air exposure and optimal time to perform the NRU assay after smoke exposure. Results showed that synthetic air exposure used in the system did not significantly alter cell survival; 24 h after smoke exposure appeared to be an optimal time-point to assess the cytotoxicity of cigarette smoke. A clear dose–response relationship between smoke exposure and cell viability was demonstrated using this system, and the evaluation method was sensitive to distinguish the differences in smoke-induced cytotoxic effects from different cigarettes. In addition, we tried converting the values of EC₅₀ from WS exposure testing into the values in unit used in total particulate matter (TPM) testing for a purpose of comparison, and the data indicate that the cytotoxicity of smoke measured by WS exposure is greater than that measured by TPM exposure.     

香烟提取物对支气管哮喘大鼠气道平滑肌细胞增殖的影响

目的： 探讨香烟提取物（CSE）对支气管哮喘(简称哮喘)大鼠气道平滑肌细胞（ASMCs）增殖作用及可能机制。方法: 16只SD大鼠随机分为对照组和哮喘组,各8只。原代培养大鼠ASMCs,取第3-6代细胞,分为对照组、对照+CSE组、哮喘组、哮喘+CSE组、哮喘+CSE+嘧啶基-苯磺酰胺（GW8510,细胞周期蛋白依赖激酶-4抑制剂）组、哮喘+GW8510组。用流式细胞术、四甲基偶氮唑盐（MTT）法及增殖细胞核抗原（PCNA）免疫细胞化学技术检测ASMCs增殖;用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹（Western blotting）检测细胞周期蛋白D1(cyclin D1)的表达。结果: （1）哮喘组ASMCs与对照组ASMCs相比,在S+G2/M期比例、吸光度（A）值和PCNA表达率上明显增高,差异显著（P＜0.01）。（2）哮喘组ASMCs S+G2/M期比例、吸光度（A）值和PCNA表达率分别为(18.30±1.12)%、0.512±0.110、(55.1±3.7)%;哮喘+CSE组分别为（32.12±1.17）%、0.801±0.210、（90.2±7.3）%;哮喘+CSE+GW8510组分别为(17.21±0.95)%、0.508±0.009、(54.3±4.8)%;哮喘+GW8510组分别为(11.16±1.48)%、0.345±0.078、(40.6±5.4)%。除哮喘组、哮喘+CSE+GW8510组两组比较差异无显著外,其余两两比较差异均显著（P＜0.01）。（3）哮喘组、哮喘+CSE组、哮喘+CSE+GW8510组、哮喘+GW8510组ASMCs cyclin D1 mRNA A值比值和蛋白表达A值比值分别为0.236±0.045、0.271±0.002;0.369±0.124、0.379±0.002;0.231±0.075、0.261±0.002;0.165±0.064、0.193±0.002。除哮喘组、哮喘+CSE+GW8510组两组比较差异无显著外,其余两两比较差异均显著（P＜0.01）。结论: 正常与哮喘大鼠ASMCs在CSE干预后增殖明显加快,cyclin D1表达明显增加。CSE可能是通过cyclin D1参与调控哮喘大鼠ASMCs的增殖。     

Murine lung response to kaolin conveyed by cigarette smoke

Summary The effects of chronic (3 to 8.5 months) smoke inhalation from cigarettes laced with 0.1, 1.0 and 10.0 mg kaolin (hydrated aluminum silicate) per gram of tobacco on the morphological integrity of lungs and the pulmonary macrophage population were evaluated in young and old male C57BL/6 mice. Lacing procedures, monitored by determining aluminum content in acid-digested aliquots of tobacco via atomic absorption spectrometry (AAS), proved to be uniform. Amounts of aluminum in right lungs of young mice evaluated by AAS and of kaolin assessed by electron diffraction and polarizing light microscopy were larger in mice which inhaled smoke from cigarettes laced with more kaolin. A more pronounced increase in lung parenchymal tissue and decrease of alveolar space was observed in old mice subjected to smoke from cigarettes containing higher doses of kaolin than in similarly treated young animals. Concomitant with the above, the lung macrophage population did not increase as markedly in response to smoke inhalation in old mice nor did it increase in as clear a dose-response fashion to kaolin as it did in young animals. Further, the degree of ultrastructural alteration of the phagocytes in the old mice suggested impaired cell function. Plate-like material resembling kaolin crystals was most conspicuous in lung macrophages of mice which inhaled largest amounts of kaolin. Manifestations of abnormal aggregates of lymphocytes and macrophages correlated with kaolin dose inhaled in old mice but not in young animals. The reported observations indicate that 1) kaolin gains access to lungs via cigarette smoke inhalation, 2) macrophages are important in maintaining pulmonary homeostasis and 3) the inorganic compound kaolin appears to impede macrophage function, resulting in potentiation of lung abnormalities.     

Exposure to cigarette smoke and Chlamydia pneumoniae infection in mice: Effect on infectious burden,systemic dissemination and cytokine responses: A pilot study

Cigarette smoke exposure has been considered a risk factor for infection with Chlamydia pneumoniae. C. pneumoniae infection is associated with respiratory tract infection and chronic respiratory disease, which is a serious public health concern. To determine whether prior exposure to cigarette smoke worsens C. pneumoniae infection (specifically, increases infectious burden and systemic dissemination) as well as alters cytokine responses in mice, adult female C57BL/6 mice were exposed to either filtered air (FA) or mainstream cigarette smoke (MCS) (15?mg/m³, total suspended particulates) for 5 days/week for 2 weeks and then infected with C. pneumoniae (10⁵ IFU) via intratracheal instillation. Mice were euthanized on Days 7, 14 or 26 post-infection (p.i.). Chlamydial burdens in the lungs and spleen were quantified by quantitative PCR (qPCR) and histologic analyses were performed; cytokine levels (TNFα, IL-4, IFNγ) in bronchoalveolar lavage fluid and serum were assayed by enzyme-linked immunosorbent assay (ELISA). The results indicated that: (1) mice exposed to either FA or MCS had similar chlamydial burdens in the lungs and spleen on Days 14 and 26?p.i.; (2) proximal and distal airway inflammation was observed on Day 14?p.i. in both FA and MCS mice, but persisted in MCS mice until Day 26?p.i.; FA exposed mice demonstrated resolution of distal airway inflammation; and (3) MCS mice displayed higher serum levels of IFNγ and IL-4 on Day 26?p.i. These findings indicate that exposure of mice to MCS (at a concentration equivalent to smoking?<?1 pack cigarettes/day) led to greater C. pneumoniae-induced inflammation, as indicated by prolonged inflammatory changes.     

A review of in vitro cigarette smoke exposure systems

In vitro test methods may be vital in understanding tobacco smoke, the main toxicants responsible for adverse health effects, and elucidating disease mechanisms. There is a variety of ‘whole smoke’ exposure systems available for the generation, dilution and delivery of tobacco smoke in vitro; these systems can be procured commercially from well-known suppliers or can be bespoke set-ups. These exposure technologies aim to ensure that there are limited changes in the tobacco smoke aerosol from generation to exposure. As the smoke aerosol is freshly generated, interactions in the smoke fractions are captured in any subsequent in vitro analysis. Of the commercially available systems, some have been characterised more than others in terms of published scientific literature and developed biological endpoints. Others are relatively new to the scientific field and are still establishing their presence. In addition, bespoke systems are widely used and offer a more flexible approach to the challenges of tobacco smoke exposure.In this review, the authors present a summary of the major tobacco smoke exposure systems available and critically review their function, set-up and application for in vitro exposure scenarios. All whole smoke exposure systems have benefits and limitations, often making it difficult to make comparisons between set-ups and the data obtained from such diverse systems. This is where exposure and dose measurements can add value and may be able to provide a platform on which comparisons can be made. The measurement of smoke dose, as an emerging field of research, is therefore also discussed and how it may provide valuable and additional data to support existing whole smoke exposure set-ups and aid validation efforts.     

Bronchial Reactivity in Relation to Immune Responses in Rats after Subcutaneous Sensitization without Adjuvant

Rats of BN×Wi/Fu strain were immunized by daily subcutaneous (S.C.) injections of antigen without the use of adjuvant for two 2-week periods with a 4-week interval. The bronchial responses to airway and intravenous (i.v.) antigen challenge were measured during and after the immunization period. These responses were compared with both the humoral and the cell-mediated immune response of the animals. Immunization induced bronchial reactivity of the animals to antigen after airway and i.v. challenge. This reactivity persisted for 7 weeks following the second immunization period. Specific IgE antibodies were detected in serum, bronchial fluid and in supernatants from cultured peripheral lymph node cells. The immunization also resulted in an IgG antibody response. Neither the amount of IgE. IgG2a, nor of any other isotype, correlated with the bronchial reactivity in the animals. Antigen simulation of lymph node cells mixed with syngeneic spleen cells induced proliferation. This procedure also resulted in a maturation of mast cells in 3-week cultures. The immunization also resulted in some increase in the number of mast cells around vessels in the lung. There was no correlation between these parameters of cell-mediated immunity and either antibody responses or bronchial reactivity.     

香烟烟气提取物对NR8383细胞吞噬功能的影响

Objective To investigate the phagocytosis function of cigarette smoke extracts (CSE)on the NR8383 cells. Methods The concentration of CSE and the optimal time was defined by cell counting kit-8 assay, Annexin V/PI cell apoptosis assay and CFSE cell proliferation assay. The cell was gained after exposed to the different concentration of CSE for 24 h and mixed with fluorescein-labeled Escherichia coli in 37℃ for 2 h. The fluorescence intensity was used to assay the phagocytosis function of NR8383 cells.Results The phagocytosis function of NR8383 cells may be changed by the concentration of CSE. In the concentration of 100 μg/ml, the phagocytosis function of NR8383 was enhanced 0.5 times than the normal cell when NR8383 cell was exposed to CSE, and the specific activity is the highest. When NR8383 cells were exposed to CSE and LPS, the phagocytosis function of NR8383 cells was enhanced 2 times than the normal cell. In the concentration of 200 μg/ml, the phagocytosis function of NR8383 cells was damaged, the rate of apoptosis is the 54. 1%. Conclusion Low concentration of CSE enhanced the phagocytosis function of NR8383 cells, but high concentration of CSE damaged the phagocytosis function of NR8383 cells. This study reveals a new role of CSE as an activator of macrophage function.     

香烟烟气提取物对NR8383细胞吞噬功能的影响

Objective To investigate the phagocytosis function of cigarette smoke extracts (CSE)on the NR8383 cells. Methods The concentration of CSE and the optimal time was defined by cell counting kit-8 assay, Annexin V/PI cell apoptosis assay and CFSE cell proliferation assay. The cell was gained after exposed to the different concentration of CSE for 24 h and mixed with fluorescein-labeled Escherichia coli in 37℃ for 2 h. The fluorescence intensity was used to assay the phagocytosis function of NR8383 cells.Results The phagocytosis function of NR8383 cells may be changed by the concentration of CSE. In the concentration of 100 μg/ml, the phagocytosis function of NR8383 was enhanced 0.5 times than the normal cell when NR8383 cell was exposed to CSE, and the specific activity is the highest. When NR8383 cells were exposed to CSE and LPS, the phagocytosis function of NR8383 cells was enhanced 2 times than the normal cell. In the concentration of 200 μg/ml, the phagocytosis function of NR8383 cells was damaged, the rate of apoptosis is the 54. 1%. Conclusion Low concentration of CSE enhanced the phagocytosis function of NR8383 cells, but high concentration of CSE damaged the phagocytosis function of NR8383 cells. This study reveals a new role of CSE as an activator of macrophage function.     

香烟烟雾提取物对哮喘大鼠气道平滑肌细胞蛋白激酶C活性的影响

目的：研究香烟烟雾提取物（CSE）对哮喘大鼠气道平滑肌细胞（ASMC）蛋白激酶C（PKC）活性的影响。 方法： 24只Wistar大鼠随机分为哮喘干预组（A组）、单纯哮喘组（B组）、对照干预组（C组）及对照组（D组），用5％ 浓度的CSE干预A、C两组ASMC，分别于干预0、1、2、3和6 h后，分离ASMC，提取胞浆及胞膜PKC，然后用［γ-32P］-ATP催化活性测定法检测PKC的活性。结果:（1）ASMC胞膜、胞浆PKC活性及两者比值：在1 h及2 h时，A组显著强于B、C、D组（均P<0.01）；B、C组显著强于D组（P<0.01，P<0.05）；B组与C组在1 h、2 h时均无显著差异。而B组与C组在1 h、2 h时差异均无显著(P＞0.05)。（2）组内ASMC胞膜、胞浆PKC活性比值：A、B、C 3组：1 h显著高于0 h、2 h（均P<0.01）；B组：2 h显著高于0 h（P<0.05）。 结论:CSE可能通过改变PKC的活性而进一步影响哮喘及其它呼吸系统疾病的发生、发展。     

Increased specific airway reactivity of persons with mild allergic asthma after 7.6 hours of exposure to 0.16 ppm ozone

BACKGROUND: Exposure to ozone causes decrements in lung function, increased airway reactivity to nonspecific bronchoconstrictors, and lung inflammation. Epidemiology studies show an association between ambient oxidant levels and increased asthma attacks and hospital admissions. OBJECTIVE: The purpose of our study was to evaluate the response of persons with mild asthma to inhaled allergen after ozone exposure conditions similar to those observed in urban areas of the United States. METHODS: Using a double-blind, counter-balanced design, we exposed 9 (5 women and 4 men) subjects with mild atopic asthma (house dust mite sensitive) to clean air and to 0.16 ppm ozone for 7.6 hours; exposures were separated by a minimum of 4 weeks. During exposure, subjects performed light exercise (ventilation = 24 L/min) for 50 minutes of each hour, and pulmonary function was evaluated before and after exposures. The morning after exposure, subjects underwent bronchial challenge with inhaled house dust mite allergen (Dermatophagoides farinae). Using a series of doubling allergen concentrations, subjects inhaled 5 breaths of nebulized allergen (0.06 to 500 AU/mL) at 10-minute intervals until a minimum of a 20% decrement in FEV(1) was elicited. RESULTS: Compared with the change in FEV(1) during air exposure, there was a mean 9.1% +/- 2.5% (SEM) decrement in FEV(1) observed because of ozone (P <.01). Seven of the 9 subjects required less allergen after ozone exposure than after air exposure; there was a 0.58 mean dose shift in the doubling concentration of allergen attributable to the ozone exposure (P =.03). CONCLUSION: These findings indicate that exposure of subjects with mild atopic asthma to ozone at levels sufficient to cause modest decrements in lung function also increases the reactivity to allergen. To the extent that this effect occurs in response to ambient exposures, ozone may be contributing to the aggravation of asthma.     

香烟烟气提取物对NR8383细胞吞噬功能的影响

目的 探讨不同浓度香烟烟气提取物(CSE)对大鼠肺泡巨噬细胞(NR8383)吞噬功能的影响.方法 通过CCK-8法分析细胞比活力,Annexin-V FITC/PI双染法检测细胞凋亡以及CFSE荧光标记分析细胞的分裂增殖,来确定CSE对NR8383细胞的作用浓度和作用时间.收集经不同浓度CSE处理24 h的NR8383细胞,与FITC标记的大肠杆菌共同孵育2 h后,用流式细胞仪检测胞内荧光强度,分析CSE对细胞吞噬功能的影响.结果 NR8383细胞的吞噬功能随着CSE浓度的变化先增强后降低.单独用CSE处理NR8383细胞,在100μg/ml CSE作用下,巨噬细胞的吞噬功能与正常对照组相比提高0.5倍,此时的细胞比活力最高.在CSE和LPS共同作用下,CSE的浓度为100μg/ml时,NR8383细胞的吞噬功能提高到正常水平的3倍.而当CSE浓度达到200μg/ml时,NR8383细胞的吞噬功能受到损伤,细胞凋亡率为54.1%.结论 CSE可以影响NR8383细胞的吞噬功能,在较低浓度时可能激活巨噬细胞的吞噬功能,但较高浓度时可能对巨噬细胞的吞噬功能造成损伤,CSE可能具有激活巨噬细胞吞噬功能的潜能.

Abstract：

Objective To investigate the phagocytosis function of cigarette smoke extracts (CSE)on the NR8383 cells. Methods The concentration of CSE and the optimal time was defined by cell counting kit-8 assay, Annexin V/PI cell apoptosis assay and CFSE cell proliferation assay. The cell was gained after exposed to the different concentration of CSE for 24 h and mixed with fluorescein-labeled Escherichia coli in 37℃ for 2 h. The fluorescence intensity was used to assay the phagocytosis function of NR8383 cells.Results The phagocytosis function of NR8383 cells may be changed by the concentration of CSE. In the concentration of 100 μg/ml, the phagocytosis function of NR8383 was enhanced 0.5 times than the normal cell when NR8383 cell was exposed to CSE, and the specific activity is the highest. When NR8383 cells were exposed to CSE and LPS, the phagocytosis function of NR8383 cells was enhanced 2 times than the normal cell. In the concentration of 200 μg/ml, the phagocytosis function of NR8383 cells was damaged, the rate of apoptosis is the 54. 1%. Conclusion Low concentration of CSE enhanced the phagocytosis function of NR8383 cells, but high concentration of CSE damaged the phagocytosis function of NR8383 cells. This study reveals a new role of CSE as an activator of macrophage function.     

Reducing secondhand smoke exposure among children and adolescents: emerging issues for intervening with medically at-risk youth

Objective To summarize information on rates of secondhandsmoke (SHS) exposure among healthy and medically at-risk pediatricpopulations, discusses the clinical manifestations of pediatricdisease that are exacerbated by exposure, and provide an overviewof promising strategies for reducing SHS in vulnerable pediatricpopulations. Methods The success of exposure reductionand smoking cessation interventions implemented with parentsof healthy children and those with respiratory disease, in thecontext of their child's health care, is reviewed. Results Concurrentimplementation of multiple levels of intervention, includingclinical interventions within the medical setting, will helpto maximize the reduction in childhood SHS exposure. Conclusion Ongoingintervention research and identification of strategies to capitalizeon opportunities for providing effective SHS counseling in primarycare and specialty clinics will be critical for effective tobaccocontrol among medically at-risk children.     

Selenium-mediated reduction in the mutagenicity of cigarette smoke

Cigarette smoke contains carcinogens and mutagens and affects the health of smokers. Recently, increased research has proven the potentially protective activity of selenium (Se) against heavy metal toxicity, cancer, and other health disorders. Accordingly, we have proposed the fortification of tobacco with Se to develop safer cigarettes. As a start in evaluating any biological effects of added Se, we have determined the mutagenicity of inhaled, mainstream (MS) cigarette smoke condensate (CSC), with and without Se, in the preincubation assay of the Ames test. Initially, it was shown that Se, as sodium selenite, was not mutagenic at high concentrations (up to 80 micrograms/plate) with strains TA1538 and TA1978. Subsequently, the effects of different levels of Se, added to MS CSC, were examined with TA98, TA100, and TA1538. On the average, addition of 10 micrograms Se produced mutagenicity reductions of about 50%. Higher levels of added Se yielded further reductions. Cigarette sidestream (SS) smoke, collected between puffs, was also tested. Again, Se added to SS-CSC gave similar reductions, confirming its antimutagenic effect for both mainstream and sidestream smoke.     

Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects

Background Magnesium is a cation with smooth muscle relaxant and anti-inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. Objective To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate [AMP]) in asthmatic subjects. Objective Two separate randomized, double-blind, placebo-controlled crossover studies, each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results In the histamine study, the provocative dose required to reduce FEV₁ by 20% (PD₂₀FEV₁) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22–1.82) doubling doses at 5 min (P= 0.018), and 1.0 (0.3–1.7) doubling doses at 50 min (P= 0.01). In the AMP study, PD₂₀FEV₁ was also significantly lower at 5 min after magnesium than after saline, by 0.64 (0.12–1.16) doubling doses (P= 0.023), though this difference was not statistically significant after adjustment for differences in baseline FEV₁ on the two study days. Conclusions Inhaled magnesium did not protect against the effects of these direct and indirect bronchoconstrictor stimuli in subjects with asthma, and may have increased airway reactivity to histamine.