Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713


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Year 2013 - Volume 39  - Number 6  (November/December)


Original Article

2 - Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

Metformina sinergicamente potencializa os efeitos antiproliferativos de cisplatina e etoposídeo em linhagem de células de câncer humano de pulmão NCI-H460

Sarah Fernandes Teixeira, Isabella dos Santos Guimarães, Klesia Pirola Madeira, Renata Dalmaschio Daltoé, Ian Victor Silva, Leticia Batista Azevedo Rangel

J Bras Pneumol.2013;39(6):644-649

Abstract PDF PT PDF EN Portuguese Text

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.


3 - Descriptive analysis of and overall survival after surgical treatment of lung metastases

Análise descritiva e sobrevida global do tratamento cirúrgico das metástases pulmonares

Giana Balestro Poletti, Ivan Felizardo Contrera Toro, Thais Ferreira Alves, Eliana Cristina Martins Miranda, José Cláudio Teixeira Seabra, Ricardo Kalaf Mussi

J Bras Pneumol.2013;39(6):650-658

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Objective: To describe demographic characteristics, surgical results, postoperative complications, and overall survival rates in surgically treated patients with lung metastases. Methods: This was a retrospective analysis of 119 patients who underwent a total of 154 lung metastasis resections between 1997 and 2011. Results: Among the 119 patients, 68 (57.1%) were male and 108 (90.8%) were White. The median age was 52 years (range, 15-75 years). In this sample, 63 patients (52.9%) presented with comorbidities, the most common being systemic arterial hypertension (69.8%) and diabetes (19.0%). Primary colorectal tumors (47.9%) and musculoskeletal tumors (21.8%) were the main sites of origin of the metastases. Approximately 24% of the patients underwent more than one resection of the lesions, and 71% had adjuvant treatment prior to metastasectomy. The rate of lung metastasis recurrence was 19.3%, and the median disease-free interval was 23 months. The main surgical access used was thoracotomy (78%), and the most common approach was wedge resection with segmentectomy (51%). The rate of postoperative complications was 22%, and perioperative mortality was 1.9%. The overall survival rates at 12, 36, 60, and 120 months were 96%, 77%, 56%, and 39%, respectively. A Cox analysis confirmed that complications within the first 30 postoperative days were associated with poor prognosis (hazard ratio = 1.81; 95% CI: 1.09-3.06; p = 0.02). Conclusions: Surgical treatment of lung metastases is safe and effective, with good overall survival, especially in patients with fewer metastases.


Keywords: Neoplasm metastasis; Survival analysis; Thoracic surgery; Metastasectomy.


4 - Levels of physical activity and predictors of mortality in COPD

Níveis de atividade física e preditores de mortalidade na DPOC

Samantha Maria Nyssen, Júlia Gianjoppe dos Santos, Marina Sallum Barusso, Antônio Delfino de Oliveira Junior, Valéria Amorim Pires Di Lorenzo, Mauricio Jamami

J Bras Pneumol.2013;39(6):659-666

Abstract PDF PT PDF EN Portuguese Text

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.


5 - Nocturnal hypoxemia in children and adolescents with cystic fibrosis

Hipoxemia noturna em crianças e adolescentes com fibrose cística

Regina Terse Trindade Ramos, Maria Angélica Pinheiro Santana, Priscila de Carvalho Almeida, Almério de Souza Machado Júnior, José Bouzas Araújo-Filho, Cristina Salles

J Bras Pneumol.2013;39(6):667-674

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Objective: To determine the prevalence of nocturnal hypoxemia and its association with pulmonary function, nutritional status, sleep macrostructure, and obstructive respiratory events during sleep in a population of clinically stable children and adolescents with cystic fibrosis (CF). Methods: This was a cross-sectional study involving 67 children and adolescents with CF between 2 and 14 years of age. All of the participants underwent polysomnography, and SpO2 was measured by pulse oximetry. We also evaluated the Shwachman-Kulczycki (S-K) scores, spirometry findings, and nutritional status of the patients. Results: The study involved 67 patients. The mean age of the patients was 8 years. The S-K scores differed significantly between the patients with and without nocturnal hypoxemia, which was defined as an SpO2 < 90% for more than 5% of the total sleep time (73.75  6.29 vs. 86.38  8.70; p < 0.01). Nocturnal hypoxemia correlated with the severity of lung disease, FEV1 (rs = −0.42; p = 0.01), FVC (rs = −0.46; p = 0.01), microarousal index (rs = 0.32; p = 0.01), and apnea-hypopnea index (rs = 0.56; p = 0.01). Conclusions: In this sample of patients with CF and mild-to-moderate lung disease, nocturnal oxygenation correlated with the S-K score, spirometry variables, sleep macrostructure variables, and the apnea-hypopnea index.


Keywords: Cystic fibrosis; Sleep; Oximetry.


6 - Can the single-breath helium dilution method predict lung volumes as measured by whole-body plethysmography?

Pode o método de diluição do hélio em respiração única estimar os volumes pulmonares medidos pela pletismografia de corpo inteiro?

Patrícia Chaves Coertjens, Marli Maria Knorst, Anelise Dumke, Adriane Schmidt Pasqualoto, João Riboldi, Sérgio Saldanha Menna Barreto

J Bras Pneumol.2013;39(6):675-685

Abstract PDF PT PDF EN Portuguese Text

Objective: To compare TLC and RV values obtained by the single-breath helium dilution (SBHD) method with those obtained by whole-body plethysmography (WBP) in patients with normal lung function, patients with obstructive lung disease (OLD), and patients with restrictive lung disease (RLD), varying in severity, and to devise equations to estimate the SBHD results. Methods: This was a retrospective cross-sectional study involving 169 individuals, of whom 93 and 49 presented with OLD and RLD, respectively, the remaining 27 having normal lung function. All patients underwent spirometry and lung volume measurement by both methods. Results: TLC and RV were higher by WBP than by SBHD. The discrepancy between the methods was more pronounced in the OLD group, correlating with the severity of airflow obstruction. In the OLD group, the correlation coefficient of the comparison between the two methods was 0.57 and 0.56 for TLC and RV, respectively (p < 0.001 for both). We used regression equations, adjusted for the groups studied, in order to predict the WBP values of TLC and RV, using the corresponding SBHD values. It was possible to create regression equations to predict differences in TLC and RV between the two methods only for the OLD group. The TLC and RV equations were, respectively, ∆TLCWBP-SBHD in L = 5.264 − 0.060 × FEV1/FVC (r2 = 0.33; adjusted r2 = 0.32) and ∆RVWBP-SBHD in L = 4.862 − 0.055 × FEV1/FVC (r2 = 0.31; adjusted r2 = 0.30). Conclusions: The correction of TLC and RV results obtained by SBHD can improve the accuracy of this method for assessing lung volumes in patients with OLD. However, additional studies are needed in order to validate these equations.


Keywords: Plethysmography, whole body; Total lung capacity; Residual volume.


7 - Barium swallow study in routine clinical practice: a prospective study in patients with chronic cough

Estudo radiográfico com ingestão de bário na rotina clínica: um estudo prospectivo em pacientes com tosse crônica

Carlos Shuler Nin, Edson Marchiori, Klaus Loureiro Irion, Artur de Oliveira Paludo, Giordano Rafael Tronco Alves, Daniela Reis Hochhegger, Bruno Hochhegger

J Bras Pneumol.2013;39(6):686-691

Abstract PDF PT PDF EN Portuguese Text

Objective: To assess the routine use of barium swallow study in patients with chronic cough. Methods: Between October of 2011 and March of 2012, 95 consecutive patients submitted to chest X-ray due to chronic cough (duration > 8 weeks) were included in the study. For study purposes, additional images were obtained immediately after the oral administration of 5 mL of a 5% barium sulfate suspension. Two radiologists systematically evaluated all of the images in order to identify any pathological changes. Fisher's exact test and the chi-square test for categorical data were used in the comparisons. Results: The images taken immediately after barium swallow revealed significant pathological conditions that were potentially related to chronic cough in 12 (12.6%) of the 95 patients. These conditions, which included diaphragmatic hiatal hernia, esophageal neoplasm, achalasia, esophageal diverticulum, and abnormal esophageal dilatation, were not detected on the images taken without contrast. After appropriate treatment, the symptoms disappeared in 11 (91.6%) of the patients, whereas the treatment was ineffective in 1 (8.4%). We observed no complications related to barium swallow, such as contrast aspiration. Conclusions: Barium swallow improved the detection of significant radiographic findings related to chronic cough in 11.5% of patients. These initial findings suggest that the routine use of barium swallow can significantly increase the sensitivity of chest X-rays in the detection of chronic cough-related etiologies.


Keywords: Barium sulfate; Cough; Contrast media; Radiography, thoracic.


8 - Immunohistochemical and morphometric evaluation of COX‑1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

Avaliação imuno-histoquímica e morfométrica de COX-1 e COX-2 no remodelamento pulmonar na fibrose pulmonar idiopática e na esclerose sistêmica

J Bras Pneumol.2013;39(6):692-700

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Objective: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. Methods: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. Results: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. Conclusions: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.


Keywords: Scleroderma, systemic; Idiopathic pulmonary fibrosis; Inflammation; Survival rate.


9 - CT densitovolumetry in children with obliterative bronchiolitis: correlation with clinical scores and pulmonary function test results

Densitovolumetria pulmonar por TC em crianças com bronquiolite obliterante: correlação com escores clínicos e testes de função pulmonar

Helena Mocelin, Gilberto Bueno, Klaus Irion, Edson Marchiori, Edgar Sarria, Guilherme Watte, Bruno Hochhegger

J Bras Pneumol.2013;39(6):701-710

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Objective: To determine whether air trapping (expressed as the percentage of air trapping relative to total lung volume [AT%]) correlates with clinical and functional parameters in children with obliterative bronchiolitis (OB). Methods: CT scans of 19 children with OB were post-processed for AT% quantification with the use of a fixed threshold of −950 HU (AT%950) and of thresholds selected with the aid of density masks (AT%DM). Patients were divided into three groups by AT% severity. We examined AT% correlations with oxygen saturation (SO2) at rest, six-minute walk distance (6MWD), minimum SO2 during the six-minute walk test (6MWT_SO2), FVC, FEV1, FEV1/FVC, and clinical parameters. Results: The 6MWD was longer in the patients with larger normal lung volumes (r = 0.53). We found that AT%950 showed significant correlations (before and after the exclusion of outliers, respectively) with the clinical score (r = 0.72; 0.80), FVC (r = 0.24; 0.59), FEV1 (r = −0.58; −0.67), and FEV1/FVC (r = −0.53; r = −0.62), as did AT%DM with the clinical score (r = 0.58; r = 0.63), SO2 at rest (r = −0.40; r = −0.61), 6MWT_SO2 (r = −0.24; r = −0.55), FVC (r = −0.44; r = −0.80), FEV1 (r = −0.65; r = −0.71), and FEV1/FVC (r = −0.41; r = −0.52). Conclusions: Our results show that AT% correlates significantly with clinical scores and pulmonary function test results in children with OB.


Keywords: Multidetector computed tomography; Respiratory function tests; Bronchiolitis obliterans.


10 - Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens

Detecção do complexo Mycobacterium tuberculosis por nested polymerase chain reaction em espécimes pulmonares e extrapulmonares

Adriana Antônia da Cruz Furini, Heloisa da Silveira Paro Pedro, Jean Francisco Rodrigues, Lilian Maria Lapa Montenegro, Ricardo Luiz Dantas Machado, Célia Franco, Haiana Charifker Schindler, Ida Maria Foschiani Dias Batista, Andrea Regina Baptista Rossit

J Bras Pneumol.2013;39(6):711-718

Abstract PDF PT PDF EN Portuguese Text

Objective: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. Methods: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. Results: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). Conclusions: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis.


Keywords: Tuberculosis/diagnosis; Tuberculosis/microbiology; Mycobacterium tuberculosis; Polymerase chain reaction.


11 - Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

Marcadores inflamatórios e imunogenéticos e sua relação com tuberculose pulmonar

Beatriz Lima Alezio Muller, Daniela Maria de Paula Ramalho, Paula Fernanda Gonçalves dos Santos, Eliene Denites Duarte Mesquita, Afranio Lineu Kritski, Martha Maria Oliveira

J Bras Pneumol.2013;39(6):719-727

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Objective: To describe serum levels of the cytokines IL-10, TNF-, and IFN-, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis. Methods: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts. Results: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN- levels and low IL-10 levels. IFN- and TNF- gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels. Conclusions: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment


Keywords: Tuberculosis; Cytokines; Immune system; Polymorphism, single nucleotide.


Review Article

12 - Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

Interpretação da positividade de autoanticorpos na doença pulmonar intersticial e colagenose pulmão dominante

Daniel Antunes Silva Pereira, Alexandre de Melo Kawassaki, Bruno Guedes Baldi

J Bras Pneumol.2013;39(6):728-741

Abstract PDF PT PDF EN Portuguese Text

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.


Case Report

13 - Assessment of regional lung ventilation by electrical impedance tomography in a patient with unilateral bronchial stenosis and a history of tuberculosis

Avaliação da ventilação pulmonar regional por tomografia de impedância elétrica em paciente com estenose brônquica unilateral pós-tuberculose

Liégina Silveira Marinho, Nathalia Parente de Sousa, Carlos Augusto Barbosa da Silveira Barros, Marcelo Silveira Matias, Luana Torres Monteiro, Marcelo do Amaral Beraldo, Eduardo Leite Vieira Costa, Marcelo Britto Passos Amato, Marcelo Alcantara Holanda

J Bras Pneumol.2013;39(6):742-746

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Bronchial stenosis can impair regional lung ventilation by causing abnormal, asymmetric airflow limitation. Electrical impedance tomography (EIT) is an imaging technique that allows the assessment of regional lung ventilation and therefore complements the functional assessment of the lungs. We report the case of a patient with left unilateral bronchial stenosis and a history of tuberculosis, in whom regional lung ventilation was assessed by EIT. The EIT results were compared with those obtained by ventilation/perfusion radionuclide imaging. The patient was using nasal continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea syndrome. Therefore, we studied the effects of postural changes and of the use of nasal CPAP. The EIT revealed heterogeneous distribution of regional lung ventilation, the ventilation being higher in the right lung, and this distribution was influenced by postural changes and CPAP use. The EIT assessment of regional lung ventilation produced results similar to those obtained with the radionuclide imaging technique and had the advantage of providing a dynamic evaluation without radiation exposure.


Keywords: Tomography; Electric impedance; Positive-pressure respiration; Pulmonary ventilation; Airway obstruction; Tuberculosis, pulmonary.


16 - Sarcomatoid carcinoma of the lung with brain metastases

Carcinoma sarcomatoide de pulmão com metástases cerebrais

Matheus Fernandes de Oliveira, Sílvia Conde Watanabe, Mara Patrícia Guilhermina de Andrade, José Marcus Rotta, Fernando Campos Gomes Pinto

J Bras Pneumol.2013;39(6):753-756

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17 - Intrapulmonary lymph node: a common and underrecognized tomography finding

Linfonodo intrapulmonar: um achado tomográfico comum e pouco reconhecido

Bruno Hochhegger, Daniela Quinto dos Reis Hochhegger, Klaus Irion, Ana Paula Sartori, Fernando Ferreira Gazzoni, Edson Marchiori

J Bras Pneumol.2013;39(6):757-758

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