We evaluated the effect of aminoguanidine on pulmonary oxidative stress and lung structure in an experimental model of diabetes mellitus. Thiobarbituric acid reactive substances (TBARS), histology and arterial blood gases were evaluated in animals with diabetes mellitus (DM group), animals with diabetes mellitus treated with aminoguanidine (DM+AG group), and controls. The TBARS levels were significantly higher in the DM group than in the control and DM+AG groups (2.90 ± 1.12 vs. 1.62 ± 0.28 and 1.68 ± 0.04 nmol/mg protein, respectively), as was PaCO2 when compared with that of the control group (49.2 ± 1.65 vs. 38.12 ± 4.85 mmHg), and PaO2 was significantly higher in the control group (104.5 ± 6.3 vs. 16.30 ± 69.48 and 97.05±14.02 mmHg, respectively). In this experimental model of diabetes mellitus, aminoguanidine reduced oxidative stress, structural tissue alterations, and gas exchange.

Keywords: Oxidative stress; Diabetes mellitus, experimental; Lung.

Diabetes mellitus is an endocrine/metabolic disorder characterized by hyperglycemia. Its impact on the respiratory system is characterized by functional changes and alterations in gas exchange. The objective of this study was to evaluate the increase in oxidative stress and the potential damages to the lung structure in an experimental model of streptozotocin-induced diabetes. We conducted histological, biochemical and blood gas analyses in the lungs of diabetic rats. We concluded that the effects of experimental diabetes mellitus include oxidative stress, structural changes in the lung tissue and altered gas exchange.

Keywords: Lung; Diabetes mellitus; Oxidative stress; Diabetes mellitus, experimental; Free radicals.

Objective: To use an experimental model to evaluate the effect of heart failure on oxidative stress in the rat diaphragm. Methods: The model of myocardial infarction was developed through left coronary artery ligation. On day 42 after coronary artery ligation, the animals were killed, after which the diaphragms were collected and homogenized. Oxidative stress was evaluated in diaphragm homogenates through measurement of lipid peroxidation and assays of the activity of antioxidant enzymes, including catalase and glutathione peroxidase (enzymes that reduce hydrogen peroxide to water), as well as superoxide dismutase (an antioxidant enzyme that reduces superoxide anions to hydrogen peroxide). Results: The coronary artery ligation model was found to be effective in causing heart failure. In the animals submitted to coronary artery ligation, the mean infarcted area of the left ventricle was 39%. Lipid peroxidation was 217% greater in the diaphragms of ligated animals than in those of controls. The activity of catalase and glutathione peroxidase was 77% and 20% lower, respectively, in study rats than in control rats. Infarction did not modify superoxide dismutase activity. Conclusion: The results suggest that left coronary artery ligation results in oxidative stress in the diaphragm.

Keywords: Myocardial infarction; Oxidative stress; Congestive heart failure; Antioxidants; Diaphragm; Rats

Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more appropriate monitoring of disease activity, as well as leading to the development of novel therapeutic agents that will effectively prevent the progression of the disease.

Keywords: Pulmonary disease, chronic obstructive; Oxidative stress; Oxidants; Antioxidants; Inflammation.

Objective: Mechanical ventilation (MV) itself can directly contribute to lung injury. Therefore, the aim of the present study was to investigate early biomarkers concerning oxidant/antioxidant balance, oxidative stress, and inflammation caused by short-term MV in healthy mouse lungs. Methods: Twenty male C57BL/6 mice were randomly divided into two groups: MV, submitted to low tidal volume (VT, 6 mL/kg) MV for 30 min; and spontaneous respiration (SR), used as controls. Lung homogenate samples were tested regarding the activity of various antioxidant enzymes, lipid peroxidation, and TNF-α expression. Results: In comparison with the SR group, the MV group showed a significant decrease in the activity of superoxide dismutase (≈35%; p < 0.05), together with an increase in the activity of catalase (40%; p < 0.01), glutathione peroxidase (500%; p < 0.001), and myeloperoxidase (260%; p < 0.001), as well as a reduction in the glutathione/oxidized glutathione ratio (≈50%; p < 0.05) and an increase in TNF-α expression in the MV group. Oxidative damage, assessed by lipid peroxidation, was also greater in the MV group (45%; p < 0.05). Conclusions: Our results show that short-term low VT MV can directly contribute to lung injury, generating oxidative stress and inflammation in healthy mouse lungs.

Keywords: Lesão pulmonar induzida por ventilação mecânica; Respiração artificial; Estresse oxidativo; Inflamação; Camundongos.

Objective: To evaluate the effects that early and late systemic administration of methylprednisolone have on lungs in a rat model of brain death. Methods: Twenty-four male Wistar rats were anesthetized and randomly divided into four groups (n = 6 per group): sham-operated (sham); brain death only (BD); brain death plus methylprednisolone (30 mg/kg i.v.) after 5 min (MP5); and brain death plus methylprednisolone (30 mg/kg i.v.) after 60 min (MP60). In the BD, MP5, and MP60 group rats, we induced brain death by inflating a balloon catheter in the extradural space. All of the animals were observed and ventilated for 120 min. We determined hemodynamic and arterial blood gas variables; wet/dry weight ratio; histological score; levels of thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD) activity; and catalase activity. In BAL fluid, we determined differential white cell counts, total protein, and lactate dehydrogenase levels. Myeloperoxidase activity, lipid peroxidation, and TNF-α levels were assessed in lung tissue. Results: No significant differences were found among the groups in terms of hemodynamics, arterial blood gases, wet/dry weight ratio, BAL fluid analysis, or histological score-nor in terms of SOD, myeloperoxidase, and catalase activity. The levels of TBARS were significantly higher in the MP5 and MP60 groups than in the sham and BD groups (p < 0.001). The levels of TNF-α were significantly lower in the MP5 and MP60 groups than in the BD group (p < 0.001). Conclusions:áIn this model of brain death, the early and late administration of methylprednisolone had similar effects on inflammatory activity and lipid peroxidation in lung tissue.

Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

Keywords: Lung; Methylprednisolone; Glucocorticoids; Lipid peroxidation; Antioxidant response elements.

Objective: To evaluate structural alterations of the lung in rats with diabetes mellitus (DM), by quantifying oxidative stress and DNA damage, as well as to determine the effects that exogenous superoxide dismutase (SOD) has on such alterations. Methods: A controlled experimental study involving 40 male Wistar rats, divided into four groups (10 animals each): control; SOD-only (without DM but treated with SOD); IDM-only (with streptozotocin-induced DM but untreated); and IDM+SOD (with streptozotocin-induced DM, treated with SOD). The animals were evaluated over a 60-day period, day 0 being defined as the day on which the streptozotocin-injected animals presented glycemia > 250 mg/dL. The SOD was administered for the last 7 days of that period. At the end of the study period, samples of lung tissue were collected for histopathological analysis, evaluation of tissue oxidative stress, and assessment of DNA damage. Results: There were no significant differences among the groups regarding DNA damage. In the IDM-only group, there was a significant increase in the extracellular matrix and significantly greater hyperplasia of the capillary endothelium than in the SOD-only and control groups. In addition, there were significant changes in type II pneumocytes and macrophages, suggesting an inflammatory process, in the IDM-only group. However, in the IDM+SOD group, there was a reduction in the extracellular matrix, as well as normalization of the capillary endothelium and of the type II pneumocytes. Conclusions: Exogenous SOD can reverse changes in the lungs of animals with induced DM.

Keywords: Diabetes mellitus, experimental; Oxidative stress; Lung; DNA damage.

Cystic fibrosis-related diabetes (CFRD) is the principal extra-pulmonary complication of cystic fibrosis, occurring in 15-30% of adult cystic fibrosis patients. The number of cystic fibrosis patients who develop diabetes is increasing in parallel with increases in life expectancy. The aim of this study was to review the physiopathology, clinical presentation, diagnosis and treatment of CFRD. A bibliographic search of the Medline and Latin American and Caribbean Health Sciences Literature databases was made. Articles were selected from among those published in the last twenty years. Insulin deficiency, caused by reduced β-cell mass, is the main etiologic mechanism, although insulin resistance also plays a role. Presenting features of type 1 and type 2 diabetes, CFRD typically affects individuals of approximately 20 years of age. It can also be accompanied by fasting, non-fasting or intermittent hyperglycemia. Glucose intolerance is associated with worsening of nutritional status, increased morbidity, decreased survival and reduced pulmonary function. Microvascular complications are always present, although macrovascular complications are rarely seen. An oral glucose tolerance test is recommended annually for patients ≥ 10 years of age and for any patients presenting unexplained weight loss or symptoms of diabetes. Patients hospitalized with severe diseases should also be screened. If fasting hyperglycemia persists for more than 48 h, insulin therapy is recommended. Insulin administration remains the treatment of choice for diabetes and fasting hyperglycemia. Calories should not be restricted, and patients with CFRD should be managed by a multidisciplinary team.

Keywords: Cystic fibrosis; Diabetes mellitus.

Liquid perfluorocarbon (PFC) instillation has been studied experimentally as an adjuvant therapy in the preservation of lung grafts during cold ischemia. The objective of this study was to evaluate whether vaporized PFC is also protective of lung grafts at different cold ischemia times. We performed histological analysis of and measured oxidative stress in the lungs of animals that received only preservation solution with low-potassium dextran (LPD) or vaporized PFC together with LPD. We conclude that vaporized PFC reduces the production of free radicals and the number of pulmonary structural changes resulting from cold ischemia.

Keywords: Ischemia; Reperfusion; Fluorocarbons; Lung transplantation; Oxidative stress.

Objetivo: Avaliar o dano oxidativo (oxidação lipídica, oxidação proteica, thiobarbituric acid-reactive substances [TBARS, substâncias reativas ao ácido tiobarbitúrico], e carbonilação) e inflamação (expressão de phosphorylated AMP-activated protein kinase e de phosphorylated mammalian target of rapamycin (p-AMPK e p-mTOR, respectivamente) em tecido pulmonar e músculos do diafragma em camundongos C57BL/6 machos expostos à fumaça de cigarro (FC) por 7, 15, 30, 45 ou 60 dias. Métodos: Trinta e seis camundongos machos da espécie C57BL/6 foram divididos em seis grupos (n = 6/grupo): grupo controle e 5 grupos expostos a FC por 7, 15, 30, 45 e 60 dias, respectivamente. Resultados: Comparados aos camundongos controle, os camundongos expostos à FC apresentaram menor peso corporal em 30 dias. Nos camundongos expostos à FC (comparados aos controle) as maiores diferenças (aumentos) nos níveis de TBARS foram observados no dia 7 no músculo diafragma, comparado ao dia 45 em tecido pulmonar; as maiores diferenças (aumentos) nos níveis de carbonilas foram observados no dia 7 em ambos os tipos de tecido; e os níveis de sulfidrilas foram menores, nos dois tipos de tecidos, em todos os tempos. No tecido pulmonar e no músculo diafragma, a expressão de p-AMPK exibiu um comportamento semelhante ao dos níveis de TBARS. A expressão de p-mTOR foi maior que o valor controle nos dias 7 e 15 no tecido pulmonar, assim como no dia 45 no músculo diafragma. Conclusões: Nossos dados demonstram que a exposição à FC produz dano oxidativo tanto no tecido pulmonar quanto (primariamente) no tecido muscular, tendo um efeito adicional no músculo respiratório, como é frequentemente observado em fumantes com DPOC.

Keywords: Oxidative stress; Mice; Respiratory system; Smoking; Inflammation.

Small animal models are particularly suitable for lung preservation studies, because they are simple and cost-effective. This brief communication focuses on the technical description of an ex vivo lung perfusion model in rats by means of a commercially available apparatus, which was the first to be installed in a thoracic surgery research laboratory in Brazil. The model and its preparation, together with its applications for lung preservation studies, are described in detail. All technical details can also be seen in a video posted on the website of the Brazilian Journal of Pulmonology.

Keywords: Lung transplantation; Reperfusion injury; Rats; Models, animal.

Objective: To describe the trends in tumor histology, gender and age among patients with non-small cell lung cancer (NSCLC) treated with lung resection. The histology of lung cancer has changed in developed countries, and there is still little information available on the topic for developing countries. Methods: This was a retrospective study of 1,030 patients with NSCLC treated with lung resection between 1986 and 2015 at a university hospital in southern Brazil. Differences in histology, stage, and type of surgery were analyzed by gender and for three periods (1986-1995, 1996-2005, and 2006-2015). Results: Most (64.5%) of the patients were males, and the main histological types were squamous cell carcinoma (in 40.6%) and adenocarcinoma (in 44.5%). The mean age at surgery during the first period was 56.4 years for women and 58.9 years for men, compared with 62.2 for women and 64.6 for men in the third period (p < 0.001). The proportion of females increased from 26.6% in the first period to 44.1% in the third. From the first to the third period, the proportion of patients with squamous cell carcinoma decreased from 49.6% to 34.8% overall (p < 0.001), decreasing to an even greater degree (from 38.9% to 23.2%) among men. Among the NSCLC patients in our sample, females with adenocarcinoma accounted for 11.9% in the first period and 24.0% in the third period (p < 0.001). Conclusions: As has been seen in developed countries, the rates of lung cancer in females in southern Brazil have been rising over the last three decades, although they have yet to surpass those observed for males in the region. The incidence of squamous cell carcinoma has decreased in males, approaching adenocarcinoma rates, whereas adenocarcinoma has significantly increased among women.

Keywords: Lung neoplasms; Epidemiology; Histology; Adenocarcinoma; Carcinoma, non-small-cell lung; Carcinoma, squamous cell.

Objective: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. Methods: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). Results: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. Conclusions: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity.

Keywords: Inflammation; Inhalation exposure; Tobacco smoke pollution.

Objective: To compare the influence of two different ventilation strategies-volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV)-on the functional performance of lung grafts in a canine model of unilateral left lung transplantation using donor lungs harvested after three hours of normothermic cardiocirculatory arrest under mechanical ventilation. Methods: The study comprised 40 mongrel dogs, randomized into two groups: VCV and PCV. Of the 20 recipients, 5 did not survive the transplant, and 5 died before the end of the post-transplant assessment period. The remaining 10 survivors (5 in each group) were evaluated for 360 min after lung transplantation. The functional performance of the grafts was evaluated regarding respiratory mechanics, gas exchange, and lung graft histology. Results: There were no significant differences between the groups regarding respiratory mechanics (peak inspiratory pressure, plateau pressure, mean airway pressure, dynamic compliance, and static compliance) or gas exchange variables (PaO2, venous oxygen tension, PaCO2, venous carbon dioxide tension, and the arterial-venous oxygen content difference). The histopathological findings were consistent with nonspecific acute lung injury and did not differ between the groups. Conclusions: This model of lung transplantation showed that the functional performance of lung grafts was not influenced by the ventilation strategy employed during the first six hours after reperfusion.

Keywords: Pulmonary ventilation; Respiration, artificial; Lung transplantation; Dogs; Organ preservation.

Objective: To describe orofacial muscle function in patients with severe asthma. Methods: This was a descriptive study comparing patients with severe controlled asthma (SCA) and severe uncontrolled asthma (SUA). We selected 160 patients, who completed a sociodemographic questionnaire and the 6-item Asthma Control Questionnaire (ACQ-6), as well as undergoing evaluation of orofacial muscle function. Results: Of the 160 patients evaluated, 126 (78.8%) and 34 (21.2%) presented with SCA and SUA, respectively, as defined by the Global Initiative for Asthma criteria. Regardless of the level of asthma control, the most frequent changes found after evaluation of muscle function were difficulty in chewing, oronasal breathing pattern, below-average or poor dental arch condition, and difficulty in swallowing. When the sample was stratified by FEV1 (% of predicted), was significantly higher proportions of SUA group patients, compared with SCA group patients, showed habitual open-mouth chewing (24.8% vs. 7.7%; p < 0.02), difficulty in swallowing water (33.7% vs. 17.3%; p < 0.04), and voice problems (81.2% vs. 51.9%; p < 0.01). When the sample was stratified by ACQ-6 score, the proportion of patients showing difficulty in swallowing bread was significantly higher in the SUA group than in the SCA group (66.6% vs. 26.6%; p < 0.01). Conclusions: The prevalence of changes in the stomatognathic system appears to be high among adults with severe asthma, regardless of the level of asthma control. We found that some such changes were significantly more common in patients with SUA than in those with SCA.

Keywords: Speech/physiology; Stomatognathic system/physiopathology; Asthma/complications; Deglutition disorders; Mastication/physiology.

Objective: To determine the prevalence of smoking, as well as its association with sociodemographic factors, alcohol consumption, and stress levels, among industrial workers in Brazil. Methods: This was a nationwide survey, conducted in 24 capitals in Brazil through the application of a pre-tested questionnaire. The response to the question "What is your smoking status?" was the outcome variable. To determine the associations, we performed Poisson regression analyses in which the inputs were blocks of variables: block 1 (age and marital status); block 2 (level of education and gross family income); block 3 (geographic region); and block 4 (alcohol consumption and stress level). All analyses were stratified by gender. Results: The sample consisted of 47,328 workers ≥ 18 years of age, of whom 14,577 (30.8%) were women. The prevalence of smoking was 13.0% (15.2% in men and 7.9% in women). Advancing age, alcohol consumption, and a high stress level were positively associated with smoking. A lower risk of smoking was associated with being married, having a higher level of education, and living in the northeastern region of the country (versus the southern region). Conclusions: The prevalence of smoking was greater in men than in women. Alcohol consumption and high stress levels appear to promote smoking.

Keywords: Tobacco use disorder/epidemiology; Tobacco smoking; Occupational health; Industry; Brazil.

Objective: Brain death (BD) triggers important hemodynamic and inflammatory alterations, compromising the viability of organs suitable for transplantation. To better understand the mi-crocirculatory alterations in donor lungs caused by BD. The present study investigated the pul-monary microcirculation in a rodent model of BD via intravital microscopy. Methods: Male Wistar rats were anaesthetized and mechanically ventilated. They were trepanned and BD was induced through the increase in intracranial pressure. As control group, sham-operated (SH) rats were trepanned only. In both groups, expiratory O2 and CO2 were monitored and after three hours, a thoracotomy was performed, and a window was created to observe the lung surface using an epi-fluorescence intravital microscopy. Lung expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) was evaluated by immunohistochemistry, and cytokines were measured in lung samples. Results: Three hours after the surgical proce-dures, pulmonary perfusion was 73% in the SH group. On the other hand, BD animals showed an important decrease in organ perfusion to 28% (p = 0.036). Lung microcirculatory compromise after BD induction was associated with an augmentation of the number of leukocytes recruited to lung tissue, and with a reduction in eNOS expression and an increase in ICAM-1 expression on lung endothelial cells. BD rats showed higher values of expiratory O2 and lower values of CO2 in comparison with SH animals after three hours of monitoring. Conclusion: Data presented showed that BD triggers an important hypoperfusion and inflammation in the lungs, compromis-ing the donor pulmonary microcirculation

Keywords: Brain death; Inflammation; Intravital microscopy; Lung microcirculation.

The tumor-node-metastasis (TNM) staging system for lung cancer has been modified since its first edition in the late 1960s. Its seventh edition has been recently published and, for the first time, a truly worldwide database was analyzed in order to propose modifications in the staging. Significant changes have been made in the tumor and metastasis descriptors. Although the recommendations for the node descriptor have remained unchanged, the analysis of the factors related to this descriptor suggests that modifications will be made in the future. The forthcoming revisions of the TNM staging system might take the molecular aspects of lung cancer into consideration, aiming at a more refined staging system.

Keywords: Lung neoplasms; Neoplasm staging; Epidemiologic methods.

Objective: To compare lung function between adolescents with and without substance use disorder (SUD). Methods: This was an observational, cross-sectional exploratory study. The sample consisted of 16 adolescents with SUD and 24 age-matched healthy controls. The adolescents in the clinical group were recruited from a psychiatric inpatient unit for detoxification and rehabilitation; their primary diagnosis was SUD related to marijuana, cocaine, or polysubstance use. Questionnaires and pulmonary function tests were applied for clinical evaluation. Results: We found that FVC, FEV1, and their percentages of the predicted values were significantly lower in the adolescents with SUD than in those without. Those differences remained significant after adjustment for BMI and the effects of high levels of physical activity. The largest effect size (Cohen's d = 1.82) was found for FVC as a percentage of the predicted value (FVC%), which was, on average, 17.95% lower in the SUD group. In addition, the years of regular use of smoked substances (tobacco, marijuana, and crack cocaine) correlated negatively with the FVC%. Conclusions: This exploratory study is innovative in that it demonstrates the early consequences of smoked substance use for the lung health of adolescents with SUD.

Keywords: Adolescent; Substance-related disorders; Lung/physiopathology; Respiratory tract diseases/etiology; Cocaine; Cannabis.