Objective: The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. Methods: Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-a, IL-1ß, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). Results: Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. Conclusions: The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.

Keywords: Lung transplantation; Tissue donors; Hypovolemic shock; Mesenchymal cells; Inflammation.

Objective: To evaluate whether methylene blue (MB) could minimize the effects of ischemia-reperfusion injury in the nonischemic lung on a lung transplantation rodent model. Methods: Forty female Sprague-Dawley rats were divided into 20 donors and 20 recipients. The 20 recipient rats were divided into two groups (n = 10) according to the treatment (0.9% saline vs. 1% MB solutions). All animals underwent unilateral lung transplantation. Recipients received 2 mL of saline or MB intraperitoneally prior to transplantation. After 2 h of reperfusion, the animals were euthanized and histopathological and immunohistochemical analyses were performed in the nonischemic lung. Results: There was a significant decrease in inflammation-neutrophil count and intercellular adhesion molecule-1 (ICAM-1) expression in lung parenchyma were higher in the saline group in comparison with the MB group-and in apoptosis-caspase-3 expression was higher in the saline group and Bcl-2 expression was higher in MB group. Conclusions: MB is an effective drug for the protection of nonischemic lungs against inflammation and apoptosis following unilateral lung transplantation in rats.

Keywords: Reperfusion injury; Methylene blue; Lung transplantation; Apoptosis; Inflammation.

Background: The methacholine challenge test is commonly used to evaluate bronchial responsiveness in diagnosis and follow-up of asthmatic patients. Objective: To investigate late effects of methacholine challenge on induced sputum. Methods: Ten non-smoker patients with mild or moderate stable asthma were recruited. At 12:00 p.m., patients were randomly assigned to inhale either methacholine (challenge) or physiologic saline. At 6:00 p.m., sputum induction was performed. On the second visit, one week apart, patients completed their participation in the study by undergoing another inhalation and sputum induction. Results: After methacholine, 8.6 ± 9 g of sputum were expectorated with 8.6 ± 6 million cells, 78 ± 10% were viable, and 6.8 ± 7% eosinophils. These data were not different from results obtained after saline: sputum amount = 7.6 ± 6 g, total cell count = 12.4 ± 12 million, viability = 82 ± 10%, and eosinophils = 6.6 ± 9%. Expiratory flow (PF) peak fall during sputum induction was not different: 21.4 ± 12% after methacholine and 18.4 ± 15% after saline. The PF fall observed during induction correlated with the amount of expectorated sputum (p = 0.018) and eosinophil relative number (p = 0.003). No other significant correlation between lung function measurements and sputum characteristics was found. Conclusion: A methacholine challenge carried out six hours before sputum induction does not significantly alter the cellular constituents or amount of sputum.

Keywords: Asthma. Methacholine chloride. Bronchial provocation tests.

Objective: To evaluate post-operative complications in living lobar lung transplant donors. Methods: Between September of 1999 and May of 2005, lobectomies were performed in 32 healthy lung transplant donors for 16 recipients. The medical charts of these donors were retrospectively analyzed in order to determine the incidence of post-operative complications and alterations in pulmonary function after lobectomy. Results: Twenty-two donors (68.75%) presented no complications. Among the 10 donors presenting complications, the most frequently observed complication was pleural effusion, which occurred in 5 donors (15.6% of the sample). Red blood cell transfusion was necessary in 3 donors (9.3%), and 2 donors underwent a second surgical procedure due to hemothorax. One donor presented pneumothorax after chest tube removal, and one developed respiratory infection. There were two intra-operative complications (6.25%): one donor required bronchoplasty of the middle lobe; and another required lingular resection. No intra-operative mortality was observed. Post-operative pulmonary function tests demonstrated an average reduction of 20% in forced expiratory volume in one second (p < 000.1) compared to pre-operative values. Conclusions: Lobectomy in living lung transplant donors presents high risk of post-operative complications and irreversible impairment of pulmonary function. Careful pre-operative evaluation is necessary in order to reduce the incidence of complications in living lobar lung transplant donors.

Keywords: Lung transplantation; Living donors; Pneumonectomy; Postoperative complications.

A 35 year-old black woman, previously healthy, who complained about chronic cough and shortness of breath was investigated after non-response of symptoms. Her chest X-ray and high resolution chest CT-scan were normal. She presented with abnormal spirometry, a mild restrictive disturbance. After a negative initial clinical investigation, an open lung biopsy was indicated. Multiple microscopic peribronchiolar tumorlets carcinoids - neuroendocrine cell hyperplasia was revealed. The authors emphasize the importance of an early diagnosis of this unusual entity and discuss its possible pathophysiological mechanisms.

Keywords: Lung diseases. Neuroendocrine cell. Bronchiolitis. Carcinoid. Tumorlets.

Background: Airway inflammation, acknowledged as an important feature of asthma, can be assessed by the examination of induced sputum. Objective: To determine the pattern of inflammatory cells in induced sputum from stable steroid-naïve asthmatics, in Florianópolis, Santa Catarina. Method: The induced sputum from 34 asthmatics using exclusively inhaled bronchodilators on demand was examined. The patients' clinical characteristics were obtained at visit 1, and sputum was induced at visit 2. Differential cell count was performed on Giemsa-stained cytospins. Sputum was considered to be eosinophilic if there were ³ 3% eosinophils, and neutrophilic if there were ³ 65% neutrophils. Results: Results are expressed by median and interquartile range. The total cell count was 3.4 (3.7) x 106 cells/ml, and cell viability was 80.0 (16.4) %. The proportion of neutrophils was 14.4 (22.1) %, of eosinophils 6.4 (17.2) %, of macrophages 60.3 (37.5) %, and of lymphocytes 1.1 (1.2) %. Eosinophilic sputum was observed in 24 subjects (70.6%); none of them had neutrophilic sputum. There were no significant differences between the eosinophilic and non-eosinophilic groups concerning the measured clinical outcomes, total cell count and proportions of cells in the sputum, except for the proportion of eosinophils (14.4 [19.3] vs 0.4 [1.1], p < 0.001). Conclusions: In our environment, steroid-naïve asthmatics present a higher proportion of sputum eosinophils, as compared to the established reference values. The clinical and physiological parameters analyzed were unable to predict the presence of eosinophilic inflammation of the airways.

Keywords: Asthma. Inflammation. Sputum. Eosinophils. Neutrophils.

Objective: To assess the association between smoking and abdominal fat among male blood donors. Methods: This was a cross-sectional study involving 1,235 adult male blood donors (age, 20-59 years) in the city of Cuiabá, Brazil. Socioeconomic, demographic, and anthropometric data, as well as information on the lifestyle of the participants, were collected. In this study, waist circumference and waist-to-hip ratio were used as markers of abdominal fat. The association between these two markers and smoking was analyzed by multiple linear regression in separate models, adjusted for potential confounders. Results: Of the 1,235 respondents, 273 (22.1%) reported being smokers, and, of those, 99 (36.3%) reported smoking more than 15 cigarettes per day. The average body mass index was lower among smokers than among nonsmokers (p < 0.001). In the multiple linear regression analyses, smoking was associated with waist circumference and waist-to-hip ratio for smokers of 6-10 cigarettes/day and of ≥ 11 cigarettes/day. Conclusions: In our sample, smoking was positively associated with indicators of abdominal fat, regardless of potential confounding factors, including the consumption of alcoholic beverages.

Keywords: Smoking; Obesity; Abdominal fat.

Objective: To evaluate the value of soluble urokinase-type plasminogen activator receptor (suPAR) in the diagnosis of acute exacerbation of COPD (AECOPD) and in monitoring treatment response, analyzing the relationship between suPAR and fibrinogen in AECOPD. AECOPD leads to increased airway inflammation, contributing to an exaggerated release of inflammatory mediators. Methods: We recruited 45 patients with AECOPD and 20 healthy control subjects. Medical histories were taken, and all subjects underwent clinical examination, chest X-ray, pulmonary function tests, and blood gas analysis. On day 1 (treatment initiation for the AECOPD patients) and day 14 (end of treatment), blood samples were collected for the determination of serum suPAR and plasma fibrinogen. Results: Serum levels of suPAR were significantly higher in the AECOPD group than in the control group. In the AECOPD patients, there was a significant post-treatment decrease in the mean serum suPAR level. The sensitivity, specificity, and accuracy of suPAR were 95.6%, 80.0%, and 93.0%, respectively. The Global Initiative for Chronic Obstructive Lung Disease stage (i.e., COPD severity) correlated positively and significantly with serum levels of suPAR and plasma levels of fibrinogen. Conclusions: Monitoring the serum suPAR level can be helpful in the evaluation of the COPD treatment response and might be a valuable biomarker for determining the prognosis of AECOPD. Because serum suPAR correlated with plasma fibrinogen, both markers could be predictive of AECOPD.

Keywords: Pulmonary disease, chronic obstructive/complications; Pulmonary disease, chronic obstructive/diagnosis; Receptors, urokinase plasminogen activator; Fibrinogen.

Objective: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity. Methods: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied. Results: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy. Conclusions: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.

Keywords: Carcinoma, non-small-cell lung; Drug therapy, combination; Metformin.

Objective: To identify factors associated with the minimal clinically important difference (MCID) for health-related quality of life (HRQoL) after physical conditioning in patients with COPD. Methods: Thirty-five patients were submitted to a 12-week program of physical conditioning (strength training plus low-intensity aerobic exercise). Body composition, incremental treadmill test results, endurance treadmill test results, six-minute walk test results, peripheral muscle strength, MIP, baseline dyspnea index (BDI) and Saint George's Respiratory Questionnaire (SGRQ) scores were assessed at baseline and after the program, thus allowing the variations (Δ) to be calculated. The MCID for HRQoL was defined as a reduction of ≥ 4% in the SGRQ total score. Subjects who responded to the program, achieving the MCID for HRQoL, were allocated to the responders (R) group (n = 24), and the remainder were allocated to the non-responders (NR) group (n = 11). Results: The values obtained for the following variables were significantly higher in group R than in group NR (p < 0.05): FEV1 (1.48 ± 0.54 L vs. 1.04 ± 0.34 L); VEF1/FVC (47.9 ± 11.7% vs. 35.5 ± 10.7%); PaO2 (74.1 ± 9.7 mmHg vs. 65.0 ± 8.9 mmHg); and ΔBDI, expressed as median and interquartile range (2.0 [0.0-3.5] vs. 0.0 [0.0-1.0]). The ΔBDI correlated significantly with the ΔSGRQ symptoms domain score, activity domain score and total score (r = 0.44, 0.60 and 0.62, respectively, p < 0.01 for all). After logistic regression, only ΔBDI remained as a predictor of MCID for HRQoL. Conclusions: Achieving the MCID for HRQoL after physical conditioning is associated with dyspnea reduction in COPD patients. Therefore, there is a need to develop treatment strategies designed to interrupt the dyspnea-inactivity-dyspnea cycle in such patients.

Keywords: Pulmonary disease, chronic obstructive; Quality of life; Dyspnea; Exercise; Rehabilitation.

Objective: To identify the risk factors for pulmonary complications after thoracotomy for the resection of pulmonary nodules in patients with sarcoma. Methods: A retrospective cohort study involving 68 consecutive patients diagnosed with sarcoma and submitted to a total of 174 thoracotomies for the resection of pulmonary nodules. The dependent variable was defined as the occurrence of any postoperative pulmonary complications. The independent variables were related to the patient, underlying diagnosis, and type of surgical procedure. We analyzed the data using a multivariate generalized estimating equations model with logistic link function and a symmetric correlation structure. Results: Complications were observed in 24 patients (13.8%, 95% CI: 9.0-19.8), and there was one death. The mean length of hospital stay was twice as long in the patients with postoperative complications as in those without (18.8 ± 10.0 days vs. 8.6 ± 6.0 days; p < 0.05). The variables that correlated with the outcome measure were the type of resection (wedge vs. anatomic; OR = 3.6; 95% CI: 1.5-8.8), the need for blood transfusion (OR = 9.8; 95% CI: 1.6-60.1), and the number of nodules resected (OR = 1.1; 95% CI: 1.0-1.1). The multivariate model showed an area under the ROC curve of 0.75 (95% CI: 0.65-0.85). Conclusions: Postoperative pulmonary complications were common after pulmonary nodule resection in patients with sarcoma, occurring in approximately 10% of the procedures. The occurrence of such complications can be expected when techniques other than wedge resection are employed, when blood transfusion is required, and when a great number of nodules are resected. Therefore, it is possible to identify patients at risk for pulmonary complications, who should be closely monitored in the immediate postoperative period. In such patients, all preventive measures should be taken.

Keywords: Sarcoma; Neoplasm metastasis; Risk; Thoracotomy; Thoracic surgery.

Because it has direct and indirect action on lung tissue, oleic acid (OA) has been used experimentally as a model of fat embolism and acute respiratory distress syndrome (ARDS). The aim of this study was to describe acute and chronic pulmonary lesions induced in rats by intravenous injection of OA. Male Wistar rats were injected a 0.05 ml dose of OA. Groups of 5 animals were sacrificed 2, 24, 48 hours, and 5, 10, 30, and 90 days after injection. Diffuse alveolar edema, foci of intra-alveolar hemorrhage, and foci of ischemic necrosis were observed by light microscopic from 2 to 48 hours. At this period of time, severe endothelial injuries and type II alveolar cell lesions were observed on electron microscopy. After the fifth day, no injury was observed and discrete morphological sequelae were found. The lungs of the animals sacrificed at the thirtieth and ninetieth days were identical to those of the control groups. The present model allows animal to survive, being suitable for studies on fat embolism and on ARDS.

Keywords: Oleic acid. Fat embolism. Acute respiratory distress syndrome, ARDS. Experimental model.

Objective: To evaluate third- and sixth-year medical students in Brazil in terms of their knowledge of and attitudes toward the WHO MPOWER policies to reduce tobacco use. Methods: The WHO Global Health Professions Student Survey was applied in five cohorts of medical students evaluated in their third and sixth years of medical school, between 2008 and 2015. Comparisons were drawn between the two years of medical school in terms of the proportions of students who experimented with or used tobacco products in the last 30 days prior to the survey; knowledge of and compliance with smoke-free policies on the university campus; formal training on smoking cessation strategies; and self-recognition as role models for patients/society. Results: Of the 943 students who completed the survey, approximately 6% had smoked cigarettes in the last 30 days prior to the survey. Comparing the third and sixth years of medical school, we observed a significant increase in the proportion of students who were knowledgeable about smoking cessation strategies (22.74% vs. 95.84%; p < 0.001) and in that of those who recognized their role as models for patients/society (84.5% vs. 89.7%; p = 0.023). Student knowledge of the smoking policies on the university campus was associated with an increase in self-recognition as role models (adjusted absolute difference = 6.7%; adjusted p = 0.050). Conclusions: Knowledge of smoking cessation strategies and self-recognition as role models for patients/society increase over the course of medical school and are associated with the implementation of smoke-free policies.

Keywords: World Health Organization; Education, public health professional; Students, medical; Tobacco; Capacity building; Health behavior.

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.