Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Behavior of cardiac variables in animals exposed to cigarette smoke

OBJECTIVE: To assess the behavior of cardiac variables in animals exposed to cigarette smoke. METHODS: Two groups of Wistar rats were studied as follows: control group (C), comprising 28 animals; and smoking group (S), comprising 23 animals exposed to cigarette smoke for 30 days. Left ventricular cardiac function was assessed in vivo with transthoracic echocardiography, and myocardial performance was analyzed in vitro in preparations of isolated left ventricular papillary muscle. The cardiac muscle was assessed in isometric contractions with an extracellular calcium concentration of 2.5 mmol/L. RESULTS: No statistical difference was observed in the values of the body variables of the rats and in the mechanical data obtained from the papillary muscle between the control and smoking groups. The values of left ventricular systolic diameter were significantly greater in the smoking animals than in the control animals (C= 3.39 ± 0.4 mm and S= 3.71 ± 0.51 mm, P=0.02). A significant reduction was observed in systolic shortening fraction (C= 56.7 ± 4.2% and S= 53.5 ± 5.3%, P=0.02) and in ejection fraction (C= 0.92 ± 0.02 and S= 0.89 ± 0.04, P=0.01). CONCLUSION: The rats exposed to cigarette smoke had a reduction in left ventricular systolic function, although their myocardial function was preserved.

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Tobacco experimental model to induce urinary bladder neoplasms

OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette) products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin) and the concentration of carbon dioxide (CO2) confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

Pictorial health warnings on cigarette packs and the impact on women

OBJECTIVE : To analyze the association between the pictorial graphic health warnings on cigarette packs and their impact on intention to quit smoking among women. METHODS : Population-based cross-sectional study among 265 women daily smokers in the State of Paraná in 2010. The sample size was calculated using cluster sampling. Participants were asked whether they had seen any pictorial graphic health warnings in the past 30 days, whether these warnings made them think about quitting, and intensity of these thoughts. The data was analyzed using logistic regression and the independent variables included age, educational attainment, whether they had children, whether they had attempted to quit smoking in the past 12 months, age of smoking initiation, number of cigarettes smoked per day, their town of residence, and how soon after waking do they smoke their first cigarette. RESULTS : Participants (91.7%) reported seeing the pictorial graphic health warnings in the past 30 days. Women with elementary education or below and women with some/complete high school education were more likely to think about quitting smoking after seeing the pictorial graphic health warningsthan women with higher education (OR = 4.85; p = 0.0028 and OR = 2.91; p = 0.05), respectively). Women who attempted to quit smoking in the past 12 months were more likely to think about quitting than women who had not (OR = 2.49; p = 0.001). Quit attempts within the last 12 months were associated with intensity of these thoughts (OR = 2.2; p = 0.03). CONCLUSIONS : Results show an association between pictorial graphic health warnings and intent to quit smoking among women with warnings having a greater impact among women with less education and who had attempted to quit smoking within the past year. Tobacco control strategies should be implemented across all groups of women regardless of their educational attainment.

Composition of the electrocautery smoke: integrative literature review

Abstract OBJECTIVE To identify the composition of the smoke produced by electrocautery use during surgery. METHOD Integrative review with search for primary studies conducted in the databases of the US National Library of Medicine National Institutes of Health, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences, covering the studies published between 2004 and 2014. RESULTS The final sample consisted of 14 studies grouped into three categories, namely; polycyclic aromatic hydrocarbons, volatile compounds and volatile organic compounds. CONCLUSION There is scientific evidence that electrocautery smoke has volatile toxic, carcinogenic and mutagenic compounds, and its inhalation constitutes a potential chemical risk to the health of workers involved in surgeries.

Exposure to larva migrans syndromes in squares and public parks of cities in Chile

Between November 2001 and December 2002, 600 dog fecal samples were collected in main squares and public parks of 13 cities in Chile, from the extreme north to the extreme south of the country. The samples were processed in the laboratory by centrifugal sedimentation and the Harada-Mori methods. T. canis eggs were found in 12 cities. Detection rates ranged from 1.9 to 12.5% with an average of 5.2%. Seven percent of the samples had eggs and 9.5% had rhabditoid and/or filariform larvae of Ancylostomatidae. Strongyloides stercoralis were not found. Squares and public parks in Chile pose a potential risk of exposure to visceral, ocular, and/or cutaneous larva migrans syndromes.

Association of dental enamel lead levels with risk factors for environmental exposure

OBJECTIVE: To analyze household risk factors associated with high lead levels in surface dental enamel. METHODS: A cross-sectional study was conducted with 160 Brazilian adolescents aged 14-18 years living in poor neighborhoods in the city of Bauru, southeastern Brazil, from August to December 2008. Body lead concentrations were assessed in surface dental enamel acid-etch microbiopsies. Dental enamel lead levels were measured by graphite furnace atomic absorption spectrometry and phosphorus levels were measured by inductively coupled plasma optical emission spectrometry. The parents answered a questionnaire about their children's potential early (05 years old) exposure to well-known lead sources. Logistic regression was used to identify associations between dental enamel lead levels and each environmental risk factor studied. Social and familial covariables were included in the models. RESULTS: The results suggest that the adolescents studied were exposed to lead sources during their first years of life. Risk factors associated with high dental enamel lead levels were living in or close to a contaminated area (OR = 4.49; 95% CI: 1.69;11.97); and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries (OR = 3.43; 95% CI: 1.31;9.00). Home-based use of lead-glazed ceramics, low-quality pirated toys, anticorrosive paint on gates and/or sale of used car batteries (OR = 1.31; 95% CI: 0.56;3.03) and smoking (OR = 1.66; 95% CI: 0.52;5.28) were not found to be associated with high dental enamel lead levels. CONCLUSIONS: Surface dental enamel can be used as a marker of past environmental exposure to lead and lead concentrations detected are associated to well-known sources of lead contamination.

Impact of academic exposure on health status of university students

OBJECTIVE: To assess the impact of academic life on health status of university students. METHODS: Longitudinal study including 154 undergraduate students from the Universidade de Aveiro, Portugal, with at least two years of follow-up observations. Sociodemographic and behavioral characteristics were collected using questionnaires. Students' weight, height, blood pressure, serum glucose, serum lipids and serum homocysteine levels were measured. Regression analysis was performed using linear mixed-effect models, allowing for random effects at the participant level. RESULTS: A higher rate of dyslipidemia (44.0% vs. 28.6%), overweight (16.3% vs. 12.5%) and smoking (19.3% vs. 0.0%) was found among students exposed to the academic life when compared to freshmen. Physical inactivity was about 80%. Total cholesterol, high density lipoprotein-cholesterol (HDL-C), triglycerides, systolic blood pressure, and physical activity levels were significantly associated with gender (p<0.001). Academic exposure was associated with increased low density lipoprotein-cholesterol (LDL-C) levels (about 1.12 times), and marginally with total cholesterol levels (p=0.041). CONCLUSIONS: High education level does not seem to have a protective effect favoring a healthier lifestyle and being enrolled in health-related areas does not seem either to positively affect students' behaviors. Increased risk factors for non-transmissible diseases in university students raise concerns about their well-being. These results should support the implementation of health promotion and prevention programs at universities.

Audiometric profile of civilian pilots according to noise exposure

OBJECTIVE To evaluate the audiometric profile of civilian pilots according to the noise exposure level. METHODS This observational cross-sectional study evaluated 3,130 male civilian pilots aged between 17 and 59 years. These pilots were subjected to audiometric examinations for obtaining or revalidating the functional capacity certificate in 2011. The degree of hearing loss was classified as normal, suspected noise-induced hearing loss, and no suspected hearing loss with other associated complications. Pure-tone air-conduction audiometry was performed using supra-aural headphones and acoustic stimulus of the pure-tone type, containing tone thresholds of frequencies between 250 Hz and 6,000 Hz. The independent variables were professional categories, length of service, hours of flight, and right or left ear. The dependent variable was pilots with suspected noise-induced hearing loss. The noise exposure level was considered low/medium or high, and the latter involved periods > 5,000 flight hours and > 10 years of flight service. RESULTS A total of 29.3% pilots had suspected noise-induced hearing loss, which was bilateral in 12.8% and predominant in the left ear (23.7%). The number of pilots with suspected hearing loss increased as the noise exposure level increased. CONCLUSIONS Hearing loss in civilian pilots may be associated with noise exposure during the period of service and hours of flight.

Effect of the exposure to maternal smoking during pregnancy and childhood on the body mass index until adolescence

OBJECTIVE Investigate the effect of exposure to smoking during pregnancy and early childhood on changes in the body mass index (BMI) from birth to adolescence.METHODS A population-based cohort of children (0-5 years old) from Cuiabá, Midwest Brazil, was assessed in 1999-2000 (n = 2,405). Between 2009 and 2011, the cohort was re-evaluated. Information about birth weight was obtained from medical records, and exposure to smoking during pregnancy and childhood was assessed at the first interview. Linear mixed effects models were used to estimate the association between exposure to maternal smoking during pregnancy and preschool age, and the body mass index of children at birth, childhood and adolescence.RESULTS Only 11.3% of the mothers reported smoking during pregnancy, but most of them (78.2%) also smoked during early childhood. Among mothers who smoked only during pregnancy (n = 59), 97.7% had smoked only in the first trimester. The changes in body mass index at birth and in childhood were similar for children exposed and those not exposed to maternal smoking. However, from childhood to adolescence the rate of change in the body mass index was higher among those exposed only during pregnancy than among those who were not exposed.CONCLUSIONS Exposure to smoking only during pregnancy, especially in the first trimester, seems to affect changes in the body mass index until adolescence, supporting guidelines that recommend women of childbearing age to stop smoking.

Risk factors for recurrent wheezing in infants: a case-control study

ABSTRACT OBJECTIVE To evaluate the association between recurrent wheezing and atopy, the Asthma Predictive Index, exposure to risk factors, and total serum IgE levels as potential factors to predict recurrent wheezing. METHODS A case-control study with infants aged 6-24 months treated at a specialized outpatient clinic from November 2011 to March 2013. Evaluations included sensitivity to inhalant and food antigens, positive Asthma Predictive Index, and other risk factors for recurrent wheezing (smoking during pregnancy, presence of indoor smoke, viral infections, and total serum IgE levels). RESULTS We evaluated 113 children: 65 infants with recurrent wheezing (63.0% male) with a mean age of 14.8 (SD = 5.2) months and 48 healthy infants (44.0% male) with a mean age of 15.2 (SD = 5.1) months. In the multiple analysis model, antigen sensitivity (OR = 12.45; 95%CI 1.28–19.11), positive Asthma Predictive Index (OR = 5.57; 95%CI 2.23–7.96), and exposure to environmental smoke (OR = 2.63; 95%CI 1.09–6.30) remained as risk factors for wheezing. Eosinophilia ≥ 4.0% e total IgE ≥ 100 UI/mL were more prevalent in the wheezing group, but failed to remain in the model. Smoking during pregnancy was identified in a small number of mothers, and secondhand smoke at home was higher in the control group. CONCLUSIONS Presence of atopy, positive Asthma Predictive Index and exposure to environmental smoke are associated to recurrent wheezing. Identifying these factors enables the adoption of preventive measures, especially for children susceptible to persistent wheezing and future asthma onset.

Exposure to psychosocial risk factors in the context of work: a systematic review

ABSTRACT OBJECTIVE To analyze the scientific literature about the effects of exposure to psychosocial risk factors in work contexts. METHODS A systematic review was performed using the terms “psychosocial factors” AND “COPSOQ” in the databases PubMed, Medline, and Scopus. The period analyzed was from January 1, 2004 to June 30, 2012. We have included articles that used the Copenhagen Psychosocial Questionnaire (COPSOQ) as a measuring instrument of the psychosocial factors and the presentation of quantitative or qualitative results. German articles, psychometric studies or studies that did not analyze individual or work factors were excluded. RESULTS We included 22 articles in the analysis. Individual factors, such as gender, age, and socioeconomic status, were analyzed along with work-related factors such as labor demands, work organization and content, social relationships and leadership, work-individual interface, workplace values, justice and respect, personality, health and well-being, and offensive behaviors. We analyzed the sample type and the applied experimental designs. Some population groups, such as young people and migrants, are more vulnerable. The deteriorated working psychosocial environment is associated with physical health indicators and weak mental health. This environment is also a risk factor for the development of moderate to severe clinical conditions, predicting absenteeism or intention of leaving the job. CONCLUSIONS The literature shows the contribution of exposure to psychosocial risk factors in work environments and their impact on mental health and well-being of workers. It allows the design of practical interventions in the work context to be based on scientific evidences. Investigations in specific populations, such as industry, and studies with more robust designs are lacking.