antigen-induced

Smoke inhalation dosimetry studies have been carried out on rats, using a new exposure system. A range of cigarettes, tobacco types and smoke concentrations was used. Penetration of smoke into the lungs was clearly demonstrated, and loads of total particulate matter (TPM) of up 1 mg were detected in the lower respiratory system of rats. The mass of TPM deposited was affected by the smoke concentration during exposure. Deposition of TPM in the head of the rat was low in relation to total respiratory system deposition. A pattern of predominantly lung deposition was achieved under the conditions used for this series of experiments. This pattern was not affected by changes in smoke dilution level, cigarette or tobacco type.     

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.     

Cotton smoke inhalation primes alveolar macrophages for tumor necrosis factor-alpha production and suppresses macrophage antimicrobial activities

The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mphi). Smoke inhalation led to dose-dependent impairment of respiratory gas exchange by 48 h postexposure and pulmonary edema by 96 h. Maximal effects were observed in animals ventilated with 54 breaths of cotton smoke (3-min exposure, 18 breaths/min). Macrophages were obtained at 48 h postexposure by bronchoalveolar lavage of rabbits subjected to 54 breaths of smoke or room air (control). Phagocytosis of opsonized bacteria and adherence to solid substratum were reduced in smoke-exposed mphi. Smoke inhalation primed mphi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed mphi were also primed for TNF-alpha release induced by phorbol myristate acetate, which suggests that the priming event occurred downstream of protein kinase C activation in the signal transduction pathway. Further, smoke exposure attenuated the inhibitory effects of phosphodiesterase inhibitors on LPS-induced TNF-alpha release. Thus, the priming event may be mediated through cAMP and/or protein kinase A. The data indicate that cotton smoke inhalation suppresses the antimicrobial activities of alveolar mphi and can lead to excessive mphi production of TNF-alpha. These mphi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.     

Are smokers' self-reports of inhalation a useful measure of smoke exposure

The relation between self-assessed and objective measures of inhalation was studied in 75 smokers who assigned themselves to one of four inhalation categories, and also estimated inhalation using a rating scale. The analysis of presmoking carbon monoxide concentration in expired air, and of the rise in carbon monoxide concentration over smoking, provided an objective measure of inhalation. These was a weak but significant correlation between self-rated inhalation and rise in carbon monoxide, but no correlation with the longer-term exposure measured by presmoking levels of carbon monoxide. Differences in exposure to carbon monoxide according to self-assessed inhalation category were non-significant. It is concluded that neither subjective measure of inhalation contributes usefully to the estimation of smoke exposure among smokers who inhale.     

Cross-tolerance between inhaled cannabis and intraperitoneal injections of delta9-THC

Male and female rats were exposed to Cannabis smoke or placebo once every second day for 32 days. Following these 16 trials all animals were injected once intraperitoneally with 4 mg/kg THC. After every third inhalation trial and after the injection the rats were placed on a movement sensor for 3 min. Cannabis smoke significantly reduced activity, relative to baseline scores, during the first 10 inhalation trials but by the thirteenth exposure, tolerance was evident. When the animals were injected with THC, the male rats who had been exposed to Cannabis smoke significantly increased their activity whereas the females did not alter their activity relative to the last inhalation trial. In contrast rats of both sexes that had been exposed to placebo smoke significantly decreased their activity following the injection. This intermodal cross-tolerance is discussed in terms of the role of conditioning in the development of tolerance.     

Relationship of burn-induced lung lipid peroxidation on the degree of injury after smoke inhalation and a body burn

OBJECTIVE: We compared the effect of a modest smoke inhalation injury, a burn injury alone, and a smoke inhalation injury plus a body burn, on the degree of lung oxidant-induced lipid peroxidation and lung injury. DESIGN: Prospective animal study with concurrent controls. SETTING: An animal laboratory. SUBJECTS: Forty-four adult yearling female sheep (weight range 45 to 50 kg). INTERVENTIONS: Forty-four sheep were prepared with lung and prefemoral (soft tissue) lymph fistulas. Twelve breaths of cooled smoke with tidal volume of 10 mL/kg body weight were given to 24 sheep, producing a peak blood carboxyhemoglobin of 25% to 30%. Twelve sheep also received a 15% total body surface third-degree burn. Sheep were killed at 4 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: Circulating lipid peroxidation was monitored as conjugated dienes and tracheobronchial mucosal and lung parenchyma as malondialdehyde. Antioxidant defenses were monitored by catalase activity. Lung physiologic and histologic changes were compared. We noted intense airways inflammation in both smoke inhalation groups and lung parenchymal inflammation in all groups. Lung lymph flow was modestly increased (two-fold) in the smoke inhalation groups. Alveolar water content was not significantly increased after any injury. PaO2 was decreased at 24 hrs after the smoke insult alone. Parenchymal malondialdehyde content did not increase with the smoke insult alone, but did increase from a control value of 110 +/- 20 to 270 +/- 24 nmol/g tissue by 4 hrs in the combined burn and smoke injury group, while catalase activity decreased. Airway mucosal malondialdehyde did not increase in any group. CONCLUSIONS: We conclude that alveolar capillary permeability is not increased early after a moderate smoke injury or smoke injury with burn. Lipid peroxidation is not increased in large airway or lung parenchyma with early after-smoke exposure. The addition of a burn significantly increases lung parenchymal lipid peroxidation, but the oxidant changes do not correspond with the degree of early lung dysfunction.     

Pulmonary function studies after smoke inhalation

Pulmonary function studies were performed within 72 hours of injury in seven patients with smoke inhalation injury diagnosed by positive 133Xe scintiphotographs and in eight patients with burns of similar size but with negative 133Xenon scans. The former patients showed decreased peak flow, decreased flow at 25, 50, and 75 per cent of vital capacity, and an elevated pulmonary resistance. In addition, single breath nitrogen tests revealed evidence of maldistribution of ventilation/perfusion abnormalities. Total lung capacity, functional residual capacity, and compliance (both dynamic and static) were similar in the two groups. Pulmonary function studies can be of assistance in evaluating smoke inhalation, estimating the severity, and following the course of patients with this disorder.     

Experimental studies of the effects of atmospheric pollutants]

Experimental studies in man are an indispensable complement to epidemiological studies and experimental studies on animals. They aim at understanding the mechanisms of action of the main pollutants and at knowing their thresholds of triggering of the acute effects on the respiratory system. The studies made in man involve controlled exposure to different atmospheric pollutants, with measurement of the functional respiratory repercussions, studies of modification of the cells in broncho-alveolar lavage, as well as experimental protocols that combine inhalation of allergen and exposure to atmospheric pollutants by allergic subjects. The main results that are available are reported to distinguish those from normal subjects and those who are allergic. More recent protocols are based on exposure to concentrations that are close to atmospheric concentrations or those that are met in work places. The main data in the literature are reported in this journal and concern SO2 acid aerosols, dioxides of nitrogen, ozone and diesel particles. Pathogenic hypotheses concerning the undesirable effects of atmospheric pollutants on the respiratory system are considered.     

Smoke-induced airway hyperresponsiveness to inhaled wood smoke in guinea pigs: tachykininergic and cholinergic mechanisms

The smoke-induced airway hyperresponsiveness (SIAHR) to inhaled wood smoke was investigated in anesthetized guinea pigs. Two smoke challenges (each 10 ml) separated by 30 min were delivered into the lungs by a respirator. In control animals, SIAHR was evidenced by an average bronchoconstrictive response (an increase in total lung resistance) to the second smoke challenge (SM2) that was approximately 4.3-fold greater than that to the first challenge (SM1). Pretreatment with CP-96,345 and SR-48,968 (neurokinin-1 and -2 receptor antagonists; each 1 mg/kg) in combination totally prevented this SIAHR, while pretreatment with CP-96,344 and SR48,965 (inactive enantiomers of CP-96,345 and SR-48,968, each 1 mg/kg) in combination failed to do so. Pretreatment with CP-96,345 (1 mg/kg), SR48,968 (1 mg/kg), or atropine (50 microg/kg) significantly alleviated this SIAHR. Pretreatment with phosphoramidon [an inhibitor of neutral endopeptidase (NEP); 2 mg/kg], which suppresses the degradation of tachykinins, induced an increase in airway reactivity that largely mimicked this SIAHR. The NEP activity measured in airway tissues excised 30 min after SM1 was significantly lower than that in air control value. These results suggest that 1) a prior wood smoke exposure induces an airway hyperresponsiveness to the subsequent wood smoke inhalation, 2) a tachykininergic mechanism involving both neurokinin-1 and -2 receptors is essential for, and a cholinergic mechanism is also involved in the development of this SIAHR, and 3) inactivation of airway NEP by wood smoke may contribute to this SIAHR.     

Exposure to toxic air contaminants in environmental tobacco smoke: an assessment for California based on personal monitoring data

The contribution of environmental tobacco smoke (ETS) to the exposure of adult nonsmoking Californians was determined for selected toxic air contaminants (TACs). The assessment was based on published measurements of ETS emission factors and personal exposures to volatile organic compounds. The human exposure studies were conducted in three California areas--Los Angeles, Pittsburgh/Antioch, and Woodland--between 1984 and 1990. We derived unexposed and passive population exposure distributions by randomly sampling the monitoring results for individuals classified according to exposure status (active smoker, passively exposed or unexposed to ETS during monitoring). The differences between the unexposed and passive distributions were used to estimate the ETS-only contribution for exposure to benzene, styrene, o-xylene, and m,p-xylene. Emission factors were then employed to infer the ETS-caused exposure to thirteen other compounds. The estimated arithmetic mean increments of 24-hour exposure attributable to ETS for the nonsmoking Californian population (age > or = 7) exposed to ETS are as follows (results in units of microgram m-3 exposure concentration; results using two different emission factors presented as a range): acetaldehyde 11-15; acetonitrile 7.0; acrylonitrile 0.49; benzene 1.02; 1,3-butadiene 0.75-2.3; 2-butanone 1.4; o-cresol 0.17; m,p-cresol 0.41; ethyl acrylate < 0.015; ethylbenzene 0.49-0.64; formaldehyde 6.5-8.2; n-nitrosodimethylamine 0.0028; phenol 1.4; styrene 0.36; toluene 3.1-3.2; o-xylene 0.77; m,p-xylene 0.99. The 90% confidence limits on these estimates due to the limited sample size in the studies are roughly x/ divided by 6. For four widely studied compounds, ETS is estimated to contribute the following percentages to the total inhalation exposure of all nonsmoking Californians: o-xylene 5%; m,p-xylene 3%; benzene 5%; and styrene 8%.     

Developmental regulation of the 3-methylcholanthrene- and dioxin-inducible CYP1A5 gene in chick embryo liver in vivo

Measurement of specific adducts to hemoglobin can be used to establish the dosimetry of electrophilic compounds and metabolites in experimental animals and in humans. The purpose of this study was to investigate the dose response for adduct formation and persistence in rats and mice during long-term low-level exposure to butadiene by inhalation. Adducts of 3,4-epoxy-1-butene, the primary metabolite of butadiene, with N-terminal valine in hemoglobin were determined in male B6C3F1 mice and male Sprague-Dawley rats following exposure to 0, 2, 10, or 100 ppm of 1,3-butadiene, 6 h/day, 5 days/week for 1, 2, 3, or 4 weeks. Blood samples were collected from groups of five mice and three rats at the end of each week during the 4 weeks of exposure and weekly for 3 weeks following the end of the 4-week exposure period. The increase and decrease, respectively, of the adduct levels during and following the end of the 4-week exposure followed closely the theoretical curve for adduct accumulation and removal for rats and mice, thereby demonstrating that the adducts are chemically stable in vivo and that the elimination follows the turnover of the red blood cells. The adduct level increased linearly with butadiene exposure concentration in the mice, whereas a deviation from linearity was observed in the rats. For example, after exposure to 100 ppm butadiene, the epoxybutene-hemoglobin adduct levels were about four times higher in mice than in rats; at lower concentrations of butadiene, the species difference was less pronounced. Blood concentrations of epoxybutene, estimated from hemoglobin adduct levels, were in general agreement with reported concentrations in mice and rats exposed by inhalation to 62.5 ppm. These studies show that adducts of epoxybutene with N-terminal valine in hemoglobin can be used to predict blood concentration of epoxybutene in experimental animals.     

Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced relaxation of rat pulmonary and celiac artery rings

BN rats are well-known for their high capacity for IgE production and hyperresponsiveness to exposure to allergens or other chemicals. We examined the histological changes in the nasal cavity, trachea and lungs of BN and F344 rats after the inhalation of aerosol formaldehyde (HCHO), which exerts direct toxic effects on the respiratory system. The incidence of clinical signs such as sneezing and abnormal respiration in HCHO-treated F344 rats was higher than that in HCHO-treated BN rats. The mean body weight of HCHO-treated F344 rats apparently decreased in comparison with control F344 rats, but that of HCHO-treated BN rats was not significantly different from that of control BN rats. Changes such as squamous metaplasia, stratification, degeneration and desquamation were observed by light microscopy in nasal, tracheal and bronchial mucosa in the lungs of the HCHO-treated F344 rats. In the HCHO-treated BN rats, similar but milder lesions were restricted to the nasal mucosa. Scanning electron microscopic observation supported these light microscopic observations. These results suggest that BN rats have lower sensitivity to HCHO inhalation than F344 rats.     

Transgenic mice carrying the human KRAS oncogene under the control of a thyroglobulin promoter: KRAS expression in thyroids analyzed by in situ hybridization

Indonesia as a developing country has air pollution which is mainly caused by motor vehicle emissions and industrial smoke. The most important indoor air pollution is cigarette smoke. The prevalence of smoking among Indonesian men is 45.7%. Of the population, 10.8% are ex-smokers and 43.5% are non-smokers. Among the female population, only 1.8% smoke. There are some important factors that influence the air pollution in Indonesia; this paper identifies the real problems and their impact. The paper reviews various studies that have been carried out in Indonesia which were related to ambient air quality, industrial air pollutants levels (SO2, NOx, Ox, Pb, CO, HC) in large cities in Indonesia have exceeded the acceptable level, especially in industrial trade and heavy traffic areas. The more cigarettes inhaled and the deeper the inhalation, especially the kretek cigarettes, the risk of ling function abnormality becomes greater. Smoking high dose kretek cigarettes, that is > or = 116 cigarettes/day x years, the risk of abnormal lung function is 13-fold that of a non-smoker; if added with the deep inhalation of smoke, the risk becomes 20-fold. Smoking increases the risk of occupational lung disease. The level of dust in some industrial areas exceeded the standard level and correlated with respiratory problems. The existence of industry caused by air pollution in the environment increased the incidence of obstructive airway diseases. We conclude that the main cause of air pollution in Indonesia is motor vehicle emissions, followed by industrial smoke. Cigarette smoke is also related to abnormal lung function.     

Allogeneic stem cell transplantation for multiple myeloma

Ethanol is added to unleaded gasoline as an oxygenate to decrease carbon monoxide automobile emissions. This introduces inhalation as a new possible route of environmental exposure to humans. Knowledge of the pharmacokinetics of inhaled ethanol is critical for adequately assessing the dosimetry of this chemical in humans. The purpose of this study was to characterize the pharmacokinetics of inhaled ethanol in male and female B6C3F1 mice and F344 rats and to develop a physiologically based pharmacokinetic (PBPK) model for inhaled ethanol in mice, rats, and humans. During exposure to 600 ppm for 6 hr, steady-state blood ethanol concentrations (BEC) were reached within 30 min in rats and within 5 min in mice. Maximum BEC ranged from 71 microM in rats to 105 microM in mice. Exposure to 200 ppm ethanol for 30 min resulted in peak BEC of approximately 25 microM in mice and approximately 15 microM in rats. Peak BEC of about 10 microM were measured following exposure to 50 ppm in female rats and male and female mice, while blood ethanol was undetectable in male rats. No sex-dependent differences in peak BEC at any exposure level were observed. Species-dependent differences were found following exposure to 200 and 600 ppm. A blood flow limited PBPK model for ethanol inhalation was developed in mice, rats, and humans which accounted for a fractional absorption of ethanol. Compartments for the model included the pulmonary blood and air, brain, liver, fat, and rapidly perfused and slowly perfused tissues. The PBPK model accurately simulated BEC in rats and mice at all exposure levels, as well as BEC reported in human males in previously published studies. Simulated peak BEC in human males following exposure to 50 and 600 ppm ranged from 7 to 23 microM and 86 and 293 microM, respectively. These results illustrate that inhalation of ethanol at or above the concentrations expected to occur upon refueling results in minimal BEC and are unlikely to result in toxicity.     

Effect of phenytoin on smoke inhalation injury in sheep

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2×2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oncogenic ras induces gastrin gene expression in colon cancer

BACKGROUND: Exposure to environmental tobacco smoke is associated with detrimental effects on pulmonary function in children. The authors investigated the relation between airway complications in children receiving general anesthesia and the passive inhalation of tobacco smoke. METHODS: Six hundred two children scheduled to receive general anesthesia were enrolled in this prospective study. The anesthesiologist and the recovery room nurse, unaware of the smoke exposure history, recorded the occurrence of airway complications. A history of passive smoking was assessed by measuring the urinary concentration of the major nicotine metabolite cotinine and by questionnaire. RESULTS: Airway complications occurred in 42% of the patients with urinary concentrations of cotinine > or =40 ng/ml, in 33% of the patients with concentrations of cotinine between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender of the child (P = 0.001) and the educational level of the child's mother (P = 0.0008) significantly modified the effect of the concentration of cotinine on the incidence of adverse respiratory events. CONCLUSIONS: There is a strong association between passive inhalation of tobacco smoke and airway complications in children receiving general anesthesia. The relationship is greatest for girls and for those whose mothers have a lower level of education. Passive smoking should be regarded as a risk factor in children undergoing general anesthesia.     

Differential exposure misclassification in case-control studies of environmental tobacco smoke and lung cancer

We review some of the literature on the effects of exposure misclassification on the statistical analysis of case-control studies. In particular, we focus on evidence for exposure misclassification which may be different for cases and controls in studies of environmental tobacco smoke (ETS). For example, such misclassification could induce relative risk estimates below unity for low exposure which appears to be the case in U.S. lung cancer and ETS studies. We describe procedures for systematically examining the sensitivity of dose-response statistics on exposure misclassification. The procedures demonstrate how p-values for the null hypothesis of no dose-response trend could be adjusted to account for exposure misclassification. The adjustment procedures were applied to an example based on a recently published large study of ETS and lung cancer in which a p-value for trend was reported as 0.03. In this example it is seen that modest differential exposure misclassification can induce substantial increases in the actual p-value, changing what appears to be statistically significant to decidedly nonsignificant.     

Readaptation time after photo stress. Readaptation time as a function of oxygen concentration

Optokinetic nystagmus (OKN) is used to study the eye's ReAdaptation Time (RAT) after a brief exposure to a light flash. The effects on RAT of breathing different concentrations of O2 are examined. Significant changes in RAT have been registered, showing that inhalation of 100% O2 as compared with room air, results in a shortened RAT (i.e. improvement), while inhalation of 9% O2 leads to an increased RAT (i.e. impairment). The physiology of RAT and the possible mechanisms behind the changes caused by different O2 concentrations are discussed. The findings of this group are compared with those of other studies.