Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

Keywords: Phosphopyruvate hydratase/analysis; Enzyme-linked immunosorbent assay; Immunohistochemistry; Lung neoplasms.

Objective: To determine the absolute number of serum T lymphocytes and cytokine levels and the characteristics of patients with active pulmonary tuberculosis and to assess their effect on the immune status of these patients and their diagnostic and predictive value for tuberculosis. Methods: We included 1,069 patients with active tuberculosis, 51 patients with latent tuberculosis infection, and 600 health individuals. Absolute serum T-lymphocyte counts and cytokine levels were quantified. Results: T lymphocytes were significantly reduced in patients with active tuberculosis when compared with healthy individuals. The immune function of patients gradually decreased with age and was stronger in female patients than in males. Th1 cells expressed higher levels of cytokines than did Th2 cells. Logistic regression analysis showed that reduced CD3+ T, CD8+ T, and NK cell counts, as well as reduced IL-4 and IFN-? expression, were independent influencing factors for active tuberculosis. ROC analysis showed that the sensitivity and specificity of absolute CD3+ T and CD8+ T lymphocyte counts and combined factors were significantly higher than were those of IL-4 and IFN-? for diagnosing active tuberculosis. Conclusions: Serum T-lymphocyte counts and cytokine levels can assess the immune status of tuberculosis patients; they are also useful biomarkers for predicting and diagnosing tuberculosis.

Keywords: Lymphocytes; Cytokines; Tuberculosis; Immunity.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method for the diagnosis and staging of lung disease, and its use is increasing worldwide. It has been used as a means of diagnosing lung cancer in its initial stages, and there are data supporting its use for the diagnosis of benign lung disease. The aim of this study was to share our experience with EBUS-TBNA and discuss its diagnostic value. Methods: We retrospectively analyzed the results related to 159 patients who underwent EBUS-TBNA at our pulmonary medicine clinic between 2010 and 2013. We recorded the location and size of lymph nodes seen during EBUS. Lymph nodes that appeared to be affected on EBUS were sampled at least twice. We recorded the diagnostic results of EBUS-TBNA and (for cases in which EBUS-TBNA yielded an inconclusive diagnosis) the final diagnoses after further investigation and follow-up. Results: We evaluated 159 patients, of whom 89 (56%) were male and 70 (44%) were female. The mean age was 54.6 ± 14.2 years among the male patients and 51.9 ± 11.3 years among the female patients. Of the 159 patients evaluated, 115 (84%) were correctly diagnosed by EBUS. The diagnostic accuracy of EBUS-TBNA was 83% for benign granulomatous diseases and 77% for malignant diseases. Conclusions: The diagnostic value of EBUS-TBNA is also high for benign pathologies, such as sarcoidosis and tuberculosis. In patients with mediastinal disorders, the use of EBUS-TBNA should be encouraged, primarily because it markedly reduces the need for mediastinoscopy.

Keywords: Sarcoidosis; Tuberculosis, pulmonary; Lung neoplasms; Bronchoscopy; Mediastinoscopy; Endosonography.

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild or benign symptoms of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

Keywords: Idiopathic interstitial pneumonias; Autoantibodies; Connective tissue diseases; Autoimmune diseases; Diagnosis, differential.

A significant percentage of pleural effusions remains without a diagnostic explanation. In such circumstances, the anatomical-pathological result of nonspecific chronic pleuritis should be revised. This is an important issue, not only for the pathologist, but mainly for the pneumologist, who usually makes the clinical-pathological correlation during the routine practice. Although the existence of established criteria is accepted, they are certainly subjective and make the communication by means of a common language difficult, mainly among pathologists. The authors recently studied 311 pleural biopsies with histo-pathological diagnoses of chronic nonspecific pleuritis. All specimens were reviewed and the histo-pathological parameters quantified by stereology. The patients were stratified according to the final diagnosis of their disease, including cases of chronic renal failure, vasculitis, pancreatitis, tuberculosis, cancer, and congestive cardiac failure, in this case considering the pleura as normal. This procedure allowed us to obtain a discriminating model, whose morphological subcriteria classified almost 90% of the nonspecific chronic pleuritis biopsies, according to their final clinical diagnoses, which included true nonspecific chronic pleuritis or tuberculosis pleuritis, paraneoplastic pleuritis, or even normal pleura. By adding to this model the biochemistry or differential cytology of the pleural liquid, its classificatory power reaches 99% of correctness. This study represents the result of the experience acquired over several years in the histo-pathological interpretation of pleural biopsies, based on the correlation between morphology and biochemistry and cytology of the pleural fluid.

Keywords: Biopsy, needle. Pleura/pathology. Pleura/cytology. Pleural effusion.

Objective: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. Methods: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was ≥ 90%. Results: Of the 85 cases, 36 (42.4%) were malignant, 30 (35.3%) were benign, and the results were inconclusive in 19 (22.3%). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7%, respectively, and the combined sensitivity was 80.6%. In the blood, the sensitivity was 57.1%, 71.4% and 48.6% for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77%. Conclusion: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.

Keywords: Biological tumor marker; Cyfra 21.1; CEA; CA 15.3; Pleural effusion.

Objective: To evaluate the diagnostic performance of the rapid shallow breathing index (RSBI) in predicting extubation failure among adult patients in the intensive care unit and to determine the appropriateness of the classical RSBI cut-off value. Methods: This was a prospective study conducted in the adult intensive care unit of the Botucatu School of Medicine Hospital das Clínicas. The RSBI was evaluated in 73 consecutive patients considered clinically ready for extubation. Results: The classical RSBI cut-off value (105 breaths/min/L) presented a sensitivity of 20% and a specificity of 95% (sum = 115%). Analysis of the receiver operator characteristic (ROC) curve revealed a better cut-off value (76.5 breaths/min/L), which presented a sensitivity of 66% and a specificity of 74% (sum = 140%). The area under the ROC curve for the RSBI was 0.78. Conclusions: The classical RSBI cut-off value proved inappropriate, predicting only 20% of the cases of extubation failure in our sample. The new cut-off value provided substantial improvement in sensitivity, with an acceptable loss of specificity. The area under the ROC curve indicated that the discriminative power of the RSBI is satisfactory, which justifies the validation of this index for use.

Keywords: Adult; Intensive care; ROC curve; Ventilator weaning; Diagnosis; Respiration, artificial.

Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

Keywords: Lung neoplasms; Early detection of cancer; Tomography, X-ray computed; Tobacco use disorder.

Objective: EBUS-TBNA cytological sampling is routinely performed for pathological diagnosis, mediastinal staging, and molecular testing in lung cancer patients. EBUS-TBNA samples are not formally accepted for testing programmed death-ligand 1 (PD-L1) expression. The objective of the study was to compare the feasibility, reproducibility, and accuracy of PD-L1 expression assessment in cytological specimens and histological samples. Methods: We prospectively collected histological (transbronchial forceps biopsy) and cytological (EBUS-TBNA) samples from peribronchial neoplastic lesions during an endoscopic procedure at the same target lesion for the pathological diagnosis and molecular assessment of stage IV non-small cell lung cancer (NSCLC). Results: Fifteen patients underwent the procedure. Adequate cytological samples (at least 100 neoplastic cells) were obtained in 12 cases (92.3%). Assessment of PD-L1 expression was similar between histological and cytological samples (agreement rate = 92%). Sensitivity and diagnostic accuracy of EBUS-TBNA cytological specimens were 88.9% and 100%, respectively. Conclusions: The evaluation of PD-L1 expression in EBUS-TBNA cytological specimens is feasible and presents good reproducibility when compared with routine histological samples. EBUS-TBNA cytological samples could be used for the assessment of PD-L1 expression in patients with NSCLC as a minimally invasive approach in stage IV NSCLC cancer patients.

Keywords: Ultrasonography; Biopsy, needle; Lung neoplasms; Molecular targeted therapy.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic test with a high diagnostic yield for suspicious central pulmonary lesions and for mediastinal lymph node staging. The main objective of this study was to describe the diagnostic yield of EBUS-TBNA for mediastinal lymph node staging in patients with suspected lung cancer. Methods: Prospective study of patients undergoing EBUS-TBNA for diagnosis. Patients ≥ 18 years of age were recruited between July of 2010 and August of 2013. We recorded demographic variables, radiological characteristics provided by axial CT of the chest, location of the lesion in the mediastinum as per the International Association for the Study of Lung Cancer classification, and definitive diagnostic result (EBUS with a diagnostic biopsy or a definitive diagnostic method). Results: Our analysis included 354 biopsies, from 145 patients. Of those 145 patients, 54.48% were male. The mean age was 63.75 years. The mean lymph node size was 15.03 mm, and 90 lymph nodes were smaller than 10.0 mm. The EBUS-TBNA method showed a sensitivity of 91.17%, a specificity of 100.0%, and a negative predictive value of 92.9%. The most common histological diagnosis was adenocarcinoma. Conclusions: EBUS-TBNA is a diagnostic tool that yields satisfactory results in the staging of neoplastic mediastinal lesions.

Keywords: Lung neoplasms; Bronchoscopy; Endosonography; Neoplasm staging.

Objective: To determine whether serum total IgE levels and total eosinophil counts have any relationship with the response to routine pharmacological treatment in patients with acute asthma. Methods: A cross-sectional study involving 162 patients with acute asthma. Serum total IgE levels, peripheral blood cell counts and eosinophil counts were determined. The treatment was adjusted for each patient according to the severity of asthma. Spirometry was performed at baseline and two weeks after the treatment. The patients were divided into two groups: high IgE (≥100 IU/mL) and low IgE (<100 IU/mL). We compared the two groups in terms of the relationships between baseline values and final values (percentage change) for the following parameters: FEV1, FVC, FEF25-75%, peripheral white blood cell counts and eosinophil counts. Results: There were no significant differences between the groups regarding the percentage changes of the studied parameters. Nor were there significant differences between the groups regarding FEV1, FVC, and FEF25-75% (% of the predicted values) at baseline. Conclusions: On the basis of these findings, we conclude that serum total IgE levels, peripheral white blood cell counts and eosinophil counts cannot predict the response to the pharmacological treatment of patients with acute asthma.

Keywords: Asthma/drug therapy; Eosinophils; Immunoglobulin E

Objective: To determine the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) using fluorine- 18‑deoxyglucose ([18F]-FDG) for the evaluation of a solitary pulmonary nodule (SPN). Methods: Prospective analysis of 53 consecutive patients submitted to PET/CT between March 2005 and May 2007 for the evaluation of an SPN. Of those, 32 met the criteria for inclusion in the present study. The lesions were evaluated for location, size, radiotracer uptake and maximum standardized uptake value (SUV). The FDG-PET/CT results were correlated with other predictors of malignancy (age, gender, smoking status, nodule size and nodule location). The definitive diagnosis was established through histopathology or through clinical/radiological follow-up for at least one year. Results: Fourteen malignant SPNs were found. Through analysis of the receiver operating characteristic curve, we established an SUV of 2.5 as the most appropriate cut-off point, since it correctly identified 13 of the 14 malignant SPNs. The results below that point revealed one false positive for neoplasia out of a total of 14. The semiquantitative method presented a sensitivity of 92.9%, specificity of 72.2%, positive predictive value of 72.2%, negative predictive value of 92.9% and accuracy of 81.2%. The multivariate analysis showed a statistically significant association with SPN malignancy only for nodule location in the upper lobes (p = 0.048) and SUV (p = 0.007). Conclusions: The results obtained suggest that the SUV of [18F]-FDG is a useful predictor of neoplasia in SPN, with a high negative predictive value, which allows malignancy to be safely ruled out, showing its relevance in the diagnostic approach to pulmonary nodules.

Keywords: Positron-emission tomography; Coin lesion, pulmonary; Lung neoplasms.

Objective: To describe the mortality trends for lung cancer, cancer of the trachea, and bronchial cancer in relation to gender and age brackets in Brazil. Methods: Data related to mortality between 1980 and 2003 were collected from the Brazilian Mortality Database. A trend analysis of mortality was carried out, nationwide and in selected states, using the LOWESS technique for rate smoothing and model adjustments. Results: In Brazil, the standardized mortality rate for lung cancer, cancer of the trachea, and bronchial cancer increased from 7.21/100,000 inhabitants in 1980 to 9.36/100,000 inhabitants in 2003. Specific mortality rates decreased in males in the 30-49 and 50-59 age brackets. In the 60-69 age bracket, the rates for males increased from 1980 to 1995 and declined thereafter. There was a trend toward higher mortality rates in males over 70, as well as in females over 30, throughout the period evaluated. Conclusions: The decrease in the mortality rates in younger males might have resulted from recent national interventions aimed at reducing the prevalence of smoking and reducing exposure in younger cohorts. High mortality rates in older populations remained constant due to prior tobacco use. Increased mortality rates in females are a worldwide trend and are attributable to the recent increase in smoking prevalence in females.

Keywords: Lung neoplasms/epidemiology; Mortality/trends; Brazil.

The usefulness of serum tumor markers in lung cancer is not well defined. Objective: The aim of this study is to examine the correlation between serum tumor markers and tumor extension and its prognostic value. Patients and method: From February 1995 to September 1997, 103 patients with non-small cell lung carcinoma were evaluated at the Department of Thoracic Surgery. Serum levels of CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4, and NSE were determined before treatment. Results: The serum level of CYFRA21.1 was the most frequent elevated tumor marker (55%). Patients with advanced tumor had higher mean serum level of CEA (90.8 ng/ml), CYFRA21.1 (20.3 ng/ml) and CA15.3 (56.5%) than those with localized carcinoma, respectively 10.2 ng/ml, 12.6 ng/ml and 22.2 ng/ml. Considering all serum tumor markers evaluated in this study, only patients with elevated CEA had greater chance (5.6) of presenting with advanced non-small lung carcinoma than patients with normal CEA. Overall survival was influenced by performance status (p = 0.001), tumor extension (p = 0.006), elevated serum level of CEA (p = 0.043), more than two elevated serum tumor markers (p < 0.001), and type of treatment (p < 0.001). The prognostic value of anatomical tumor extension reached the limit of significance (p = 0.052); however, two or more elevated serum tumor markers and type of treatment had independent prognostic value (respectively, p = 0.035 and p = 0.005). Conclusion: None of these serum tumor markers had clinical value in the management of NSCLC patients.

Keywords: biological tumor markers, neoplasm staging, non-small cell lung carcinoma, prognosis

Background: Lung cancer is the leading cause of cancer-related death worldwide. Objective: To determine the time spent diagnosing, staging and surgically treating lung cancer in a university hospital. Method: Between January 1990 and December 1998, 69 (53 male, 16 female) patients were diagnosed with lung cancer and underwent surgery. The hospital records of these patients were reviewed to evaluate clinical and histological data, dates of outpatient visits, hospital admission, tests and procedures, as well as to determine if the patients were examined as inpatients or as outpatients. Results: The 15 patients investigated as outpatients were designated as group I, the 28 examined as both inpatients and outpatients as group II, and the 26 investigated as inpatients as group III. Age ranged from 43 to 79 years (mean ± SD; 61 ± 10). Of the 69 patients, 43 were smokers and 23 were ex-smokers. The mean time from onset of symptoms to the first outpatient visit was 110 days and 33 days from the first outpatient visit until diagnosis. There was a lapse of 25 days between diagnosis and surgery. The mean total elapsed time between the first outpatient visit and surgery was 58 days. The mean total time was 72 days for group I, 72 days for group II, and 35 days for group III (p < 0.01). There was no significant difference regarding total time in relation to the different stages of the disease (p = 0.16). Conclusions: The results show that patients waited too long before seeking medical assistance and that medical treatment of lung cancer was further delayed when patients were examined in an outpatient setting.

Keywords: Lung neoplasm/surgery. Disease progression.

Objective: To compare the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index scores and its individual components between COPD patients with and without severe physical inactivity, as well as to correlate the number of steps/day with scores of physical activity questionnaires, age, and the BODE index (including its components). Methods: We included 30 patients, who were evaluated for body composition, pulmonary function (FEV1), perception of dyspnea (modified Medical Research Council scale), and exercise capacity (six-minute walk distance [6MWD]). The patients also completed the International Physical Activity Questionnaire (IPAQ), short version, and the modified Baecke questionnaire (mBQ). The level of physical activity was assessed by the number of steps/day (as determined by pedometer), using the cut-off of 4,580 steps/day to form two groups: no severe physical inactivity (SPI−) and severe physical inactivity (SPI+). We used the Mann-Whitney test or t-test, as well as Pearson's or Spearman's correlation tests, in the statistical analysis. Results: In comparison with the SPI− group, the SPI+ group showed more advanced age, higher mBQ scores (leisure domain), lower 6MWD (in m and % of predicted), and lower IPAQ scores (metabolic equivalent-walk/week domain and total). The IPAQ scores showed weak correlations with steps/day (r = 0.399), age (r = −0.459), and 6MWD-in m (r = 0.446) and in % of predicted (r = 0.422). Conclusions: In our sample, the cut-off of 4,580 steps/day was not sensitive enough to identify differences between the groups when compared with the predictors of mortality. The IPAQ, short version score correlated with steps/day.

Keywords: Pulmonary disease, chronic obstructive/mortality; Pulmonary disease, chronic obstructive/ prevention and control; Motor activity.

Asbestos-induced diseases are still major health problems, as a remarkably large number of workers have been exposed to asbestos over the past 50 years. Personal injury lawsuits against asbestos manufacturers number hundreds of thousands, and new cases are still being filed. Asbestosis is a complex issue, and although the broad outlines of asbestos-related diseases are well set, many important areas, especially pathology, are poorly understood. In Brazil, since 1940, asbestos has been commercially explored, producing around 200,000 tons/year, exposing about 10,000 workers in the mining activity, and an unknown number of workers in asbestos-cement industry. A study, with scientific appropriate investigation, with the purpose to evaluate the effects of asbestos exposure over the health of the mine workers in this country, was done by interinstitution researchers, and untitled "Morbidity and mortality among workers exposed to asbestos in mining activities - 1940/1996". With the experience achieved in the course of this study, the objective of this report is to make an overview of asbestos-related diseases, mainly with respect to difficulties in establishing the histopathologic diagnosis.

Keywords: Asbestosis. Pathology. Neoplasms. Diagnosis.

Carcinoma of the lung can present in a number of guises and a number of possible and often complementary diagnostic approaches are available. The choice of procedure should reflect the presentation of the tumor, local expertise, intended management and patient preference. There are different methods of investigation: sputum cytology, fiberbronchoscopy, transbronchial biopsy, transbronchial needle aspiration, transthoracic fine needle aspiration, etc. The association of all of these methods increases the power of diagnosis. Staging is the measurement of the anatomical extent of a tumor in any given patient. The staging of cancer began with Denoix's TNM classification system, and, although several modifications were developed, it remains the basis of lung cancer staging systems up to now. Assigning patients to a particular TNM stage allows choosing the most appropriate therapy and provides prognostic information. Also, the impact of new therapeutic methods can be evaluated for efficacy and a comparison of the expected survival rates can be predicted.