Objective: Although Mycobacterium avium complex (MAC) lung disease has been shown to be associated with lung cancer and hematologic malignancies, there have been few studies of its relationships with other types of cancer. The aim of this study was to assess the effect that coexisting advanced extrapulmonary solid tumors have on the progression of MAC lung disease. Methods: This was a retrospective study of patients diagnosed with MAC lung disease, on the basis of the American Thoracic Society (ATS) criteria, between October of 2005 and March of 2019. The patients were divided into three groups: those with advanced-stage cancer (A-SC group); those with early-stage cancer (E-SC group); and those without cancer (control group). Progression of MAC lung disease was defined as exacerbation seen on imaging. Patient characteristics and the time to progression were compared among the three groups. Results: A total of 286 patients met the ATS diagnostic criteria for MAC lung disease, and 128 of those were excluded. Of the remaining 158 patients, 20 (7.0%) were in the A-SC group, 36 (12.6%) were in the E-SC group, and 102 (35.7%) were in the control group. The median time to progression in the A-SC, E-SC, and control groups was 432, 3,595, and 2,829 days, respectively (p < 0.01). A proportional hazards model showed that the significant predictors of MAC lung disease progression were advanced-stage cancer (hazard ratio [HR] = 6.096; 95% CI: 2.688-13.826; p < 0.01), cavitary lesions (HR = 2.750; 95% CI: 1.306-5.791; p < 0.01), and a high Nodule-Infiltration-Cavity-Ectasis score (HR = 1.046; 95% CI: 1.004-1.091; p = 0.033). Conclusions: A coexisting advanced extrapulmonary solid tumor could hasten the progression of MAC lung disease.

Keywords: Nontuberculous mycobacteria; Mycobacterium avium complex; Neoplasms; Radiography.

Objective: The rapid differentiation between Mycobacterium tuberculosis and nontuberculous mycobacteria is fundamental for patients co-infected with tuberculosis and HIV. To that end, we use two methods in our laboratory: detection of cord factor and PCR-restriction enzyme analysis (PRA). The objective of this study was to evaluate the accuracy of a screening test on solid medium as a rapid method for the presumptive identification of M. tuberculosis complex, considering costs and turnover time. Methods: A total of 152 strains were submitted to a combined screening test, consisting of the detection of cord factor under microscopy (Ziehl-Neelsen staining) and evaluation of the macroscopic aspect of colonies, as well as to PRA, which was used as the gold standard. Costs were estimated by calculating the price of all of the materials needed for each test. Results: The overall accuracy of cord factor detection alone was 95.4% (95% CI: 90.7-98.1%), and that of the combined screening test was 99.3% (95% CI: 96.4-100%). Cord factor detection costs US$ 0.25, whereas the PRA costs US$ 7.00. Results from cord factor detection are ready in 2 days, whereas PRA requires 4 days to yield results. Conclusions: The presumptive identification of M. tuberculosis using the macroscopic evaluation of colonies combined with cord factor detection under microscopy is a simple, rapid and inexpensive test. We recommend the combined screening test to rapidly identify M. tuberculosis in resource-poor settings and in less well-equipped laboratories while awaiting a definite identification by molecular or biochemical methods.

Keywords: Tuberculosis; Mycobacterium/classification; Polymerase chain reaction; Diagnostic tests, routine.

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.

Objective: To assess the esophageal function profile and the prevalence of gastroesophageal reflux (GER) in lung transplant candidates. Methods: From July of 2005 to November of 2006, a prospective study was conducted involving 55 candidates for lung transplantation at the Santa Casa de Misericórdia Hospital in Porto Alegre, Brazil. Prior to transplantation, patients underwent outpatient stationary esophageal manometry and 24-h esophageal pH-metry using one and two electrodes. Results: Abnormal esophageal manometry was documented in 80% of the patients, and 24% of the patients presented pathological acid reflux. Digestive symptoms presented sensitivity and specificity for GER of 50% and 61%, respectively. Of the patients with chronic obstructive pulmonary disease, 94% presented abnormal esophageal manometry, and 80% presented lower esophageal sphincter hypotonia, making it the most common finding. Patients with bronchiectasis presented the highest prevalence of GER (50%). Conclusions: In patients with advanced lung disease, GER is highly prevalent. In the population studied, digestive symptoms of GER were not predictive of pathological acid reflux. The role that GER plays in chronic rejection should be examined and clarified in future studies.

Keywords: Gastroesophageal reflux; Lung transplantation; Manometry; Esophageal pH monitoring.

Objective: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. Methods: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. Results: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). Conclusions: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

Keywords: Drug therapy; Lung neoplasms; Exercise tolerance.

Objective: Nontuberculous mycobacteria (NTM) are a heterogeneous group of bacteria that are widely distributed in nature and associated with opportunistic infections in humans. The aims of this study were to identify NTM in patients with suspected tuberculosis who pre-sented positive cultures and to evaluate the genetic diversity of strains identified as Myco-bacterium avium. Methods: We studied pulmonary and extrapulmonary samples obtained from 1,248 patients. The samples that tested positive on culture and negative for the M. tu-berculosis complex by molecular identification techniques were evaluated by detection of the hsp65 and rpoB genes and sequencing of conserved fragments of these genes. All strains identified as M. avium were genotyped using the eight-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat method. Results: We found that NTM ac-counted for 25 (7.5%) of the 332 mycobacteria isolated. Of those 25, 18 (72%) were M. avium, 5 (20%) were M. abscessus, 1 (4%) was M. gastri, and 1 (4%) was M. kansasii. The 18 M. avium strains showed high diversity, only two strains being genetically related. Conclusions: These results highlight the need to consider the investigation of NTM in patients with suspected active tuberculosis who present with positive cultures, as well as to evaluate the genetic di-versity of M. avium strains.

Keywords: Mycobacterium avium; Nontuberculous mycobacteria; HIV; Genotyping techniques.

Objective: Virulent strains of the Mycobacterium tuberculosis complex, under certain appropriate conditions, grow as characteristic ropes, bundles or serpentine cords known as cord factor or growth in cords. The objective of the present study was to evaluate cord factor detection as a method of achieving presumptive identification of the M. tuberculosis complex, comparing it to conventional typing tests. Methods: A total of 743 strains were analyzed from January of 2002 to December of 2005 in the Mycobacteria Sector of the Adolfo Lutz Institute, located in the city of Santos, Brazil. Samples were obtained from clinical specimens collected from patients with respiratory symptoms treated at basic health clinics in the greater metropolitan area of Santos. Ziehl-Neelsen-stained smears were prepared, 301 (40.5%) in MB/BacT broth and 442 (59.5%) on solid media, either Lowenstein-Jensen or Ogawa-Kudoh. Results: The sensitivity, specificity, positive predictive value and negative predictive value obtained during the performance comparison of the two methods (cord factor detection and conventional typing) using both isolation media were, respectively, 98.5, 88, 97 and 93%. The method was more sensitive on solid medium (100%), and the difference in sensitivity between the two media types was only 2.7%. Conclusions: Taking into consideration the results obtained, we conclude that, in laboratories with a high incidence of M. tuberculosis complex isolation and limited economic resources, cord factor detection is a fast and valid criterion for identifying these mycobacteria using liquid or solid medium. It also enables subsequent conclusive identification tests, as well as additional sensitivity tests when necessary.

Keywords: Laboratory techniques and procedures; Mycobacterium tuberculosis; Cord factors

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.

Objective: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. Methods: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR) and ischemia-reperfusion + tramadol (IR+T). The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively). All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v.) immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p.), the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. Results: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both). Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. Conclusions: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion.

Keywords: Tramadol; Muscle, skeletal; Ischemic attack, transient; Lung Injury.

Several advances have been made in the treatment of advanced non-small cell lung cancer in the last few years. Combined therapies using chemotherapy have improved survival of patients with locally advanced disease (stage III) when compared to either radiation or surgery. New chemotherapeutic agents, used alone or combined, have also made a strong impact with metastatic disease (stage IV). Ongoing randomized trials will certainly define new treatment standards and hopefully improve the outcome of patients with non-small cell lung cancer.

Keywords: Locally advanced. Non-small cell lung cancer.

Objective: To investigate the diagnostic accuracy of a chest X-ray (CXR) score and of clinical and laboratory data in predicting the clinical course of patients with SARS coronavirus 2 (SARS-CoV-2) infection. Methods: This is a pilot multicenter retrospective study including patients with SARS-CoV-2 infection admitted to the ERs in three hospitals in Italy between February and March of 2020. Two radiologists independently evaluated the baseline CXR of the patients using a semi-quantitative score to determine the severity of lung involvement: a score of 0 represented no lung involvement, whereas scores of 1 to 4 represented the first (less severe) to the fourth (more severe) quartiles regarding the severity of lung involvement. Relevant clinical and laboratory data were collected. The outcome of patients was defined as severe if noninvasive ventilation (NIV) or intubation was necessary, or if the patient died. Results: Our sample comprised 140 patients. Most of the patients were symptomatic (132/138; 95.7%), and 133/140 patients (95.0%) presented with opacities on CXR at admission. Of the 140 patients, 7 (5.0%) showed no lung involvement, whereas 58 (41.4%), 31 (22.1%), 26 (18.6%), and 18 (12.9%), respectively, scored 1, 2, 3, and 4. In our sample, 66 patients underwent NIV or intubation, 37 of whom scored 1 or 2 on baseline CXR, and 28 patients died. Conclusions: The severity score based on CXR seems to be able to predict the clinical progression in cases that scored 0, 3, or 4. However, the score alone cannot predict the clinical progression in patients with mild-to-moderate parenchymal involvement (scores 1 and 2).

Keywords: Coronavirus infections; Radiography, thoracic; Pneumonia; Respiratory insufficiency; Severe acute respiratory syndrome.

Objective: To evaluate the performance of nested PCR (nPCR) in detecting the Mycobacterium tuberculosis complex in blood samples of patients suspected of having TB, in order to determine its potential for use as an auxiliary tool in the laboratory diagnosis of TB in children. Methods: Detection of the M. tuberculosis complex in blood samples using as a target the insertion sequence IS6110 of the genomic DNA of the bacillus. Blood samples of 120 patients were evaluated. All of the patients were under 15 years of age at the time of their treatment at public hospitals in the city of Recife, Brazil (between January of 2003 and August of 2005). Attending physicians at the hospitals diagnosed TB based on the criteria recommended by the American Thoracic Society. The nPCR amplified a 123-bp fragment with outer oligonucleotides (IS1/IS2) and, in the subsequent reaction, using inner oligonucleotides (IS3/IS4), generating an 81-bp amplicon. Results: Active or latent TB was found in 65 patients, TB was ruled out in 28 suspected cases, and 27 patients were TB-free (controls). The sensitivity of nPCR was 26.15% and was significantly higher for the extrapulmonary form of the disease (55.56%) than for the pulmonary form (18.18%). The specificity was 92.73%. Conclusions: Despite the difficulties in diagnosing TB in children and the low number of cases evaluated in the present study, nPCR in blood samples proved to be a rapid and specific technique, albeit one with low sensitivity. In order to establish its true usefulness in the diagnosis of paucibacillary forms, especially extrapulmonary TB, further studies need to be carried out with a larger sample of children and analyzing biological specimens other than blood.

Keywords: Tuberculosis; Diagnosis; Blood; Polymerase chain reaction.

Objective: To identify the role of bronchodilators in the maximal breath-hold time in patients with obstructive lung disease (OLD). Methods: We conducted a case-control study including patients with OLD and a control group. Spirometric tests were performed prior to and after the use of a bronchodilator, as were breath-hold tests, using an electronic microprocessor and a pneumotachograph as a flow transducer. Respiratory flow curves were displayed in real time on a portable computer. The maximal breath-hold times at end-inspiratory volume and at end-expiratory volume (BHTmaxVEI and BHTmaxVEE, respectively) were determined from the acquired signal. Results: A total of 35 patients with OLD and 16 controls were included. Prior to the use of a bronchodilator, the BHTmaxVEI was significantly lower in the OLD group than in the control group (22.27 ± 11.81 s vs. 31.45 ± 15.73 s; p = 0.025), although there was no significant difference between the two groups in terms of the post-bronchodilator values (24.94 ± 12.89 s vs. 31.67 ± 17.53 s). In contrast, BHTmaxVEE values were significantly lower in the OLD group than in the control group, in the pre- and post-bronchodilator tests (16.88 ± 6.58 s vs. 22.09 ± 7.95 s; p = 0.017; and 21.22 ± 9.37 s vs. 28.53 ± 12.46 s; p = 0.024, respectively). Conclusions: Our results provide additional evidence of the clinical usefulness of the breath-hold test in the assessment of pulmonary function and add to the existing knowledge regarding the role of the bronchodilator in this test.

Keywords: Respiratory function tests; Pulmonary disease, chronic obstructive; Bronchodilator agents; Apnea.

Introduction: Most of the experimental studies on amiodarone-induced pulmonary toxicity have been performed in male Fischer-344 rats. Objective: To investigate the effect of amiodarone on body weight and on lung morphological and cytopathologic parameters in both genders of other rat strains. Methods: Groups of male and female Wistar, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats received, 175 mg/kg/day of amiodarone suspended in saline by gavage for four weeks. Controls received saline alone. Body weight gain, total cellularity, and differential of the bronchoalveolar lavage (BAL) and lung histopathology were studied. Results: Mortality due to amiodarone was observed in treated WKY rats, mostly in males. Treated male and female SHR animals had less body weight gain among all strains studied. Male Wistar and SHR treated rats presented more body weight gain than females of the respective strains. BAL of treated SHR rats were hemorrhagic. BAL cellularity was higher in treated males (WKY > Wistar > SHR). In WKY males and females, however, the differential count showed a lesser percent of macrophages and higher of neutrophils than in the other strains. BAL macrophages of treated Wistar rats presented phospholipidosis, whereas most macrophages of treated SHR rats were normal. In lung anatomicopathologic examination, no difference was found related to gender and no pneumonitis was observed. In Wistar rats, the examination was characterized by a marked quantity of intra-alveolar "foamy" macrophages, numerous intraparenchymal abscesses were found in WKY rats, and alveolar hemorrhage was present in SHR rats. Conclusions: 1) amiodarone induces more foamy macrophages in Wistar rats than in the WKY and SHR strains, although they do not develop pneumonitis in the model used; 2) amiodarone has greater effect on lung morphological and cytopathologic parameters of male rats.

Objective: To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). Methods: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. Results: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. Conclusions: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

Keywords: Nontuberculous mycobacteria/classification; Nontuberculous mycobacteria/drug effects; Lung diseases.

Objectives: Non-small cell lung cancer (NSCLC) is an incidental and aggressive type of cancer. Although curative treatment can be offered, the recurrence rate is relatively high. Identifying factors that have a prognostic impact may guide changes in the staging system and recommendations for adjuvant therapy. The aim of this study was to evaluate the impact of microvascular invasion on the 5-year overall survival (OS) of patients with resected NSCLC treated at a reference cancer center. Methods: This retrospective, observational cohort study included patients diagnosed with early-stage NSCLC (clinical stages I-IIIA), treated with curative-intent surgery at the Brazilian National Cancer Institute between 2010 and 2016. Results: The dataset comprised 91 surgical patients, mostly females and white, with a mean age of 62 years (range between 29-83). Cases were distributed as stages I, II, and III in 55%, 29%, and 16%. Adenocarcinoma was the predominant histological subtype (67%), and microvascular invasion was present in 25% of the patients. The 5-year OS probability was 60% (95% CI, 48.3-68.9). Among all characteristics, advanced stages (p = 0.001) and the presence of microvascular invasion (p< 0.001) were related to a worse 5-year OS. After adjusting for age group and pathological stage, the presence of microvascular invasion was associated with a 4-fold increased risk of death (HR 3.9, 95% CI, 1.9-8.2). Conclusion: The presence of microvascular invasion was an independent factor related to worse survival and, therefore, should be routinely assessed in resected specimens.

Keywords: non-small cell lung cancer, thoracic surgery, survival analysis, microvascular invasion.