Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

Keywords: Tuberculosis, multidrug-resistant; Immunity; Pharmacogenetics; Polymerase chain reaction; Risk.

Objective: To evaluate clinical characteristics and outcomes in patients hospitalized for tuberculosis, comparing those in whom tuberculosis treatment was started within the first 24 h after admission with those who did not. Methods: This was a retrospective cohort study involving new tuberculosis cases in patients aged ≥ 18 years who were hospitalized after seeking treatment in the emergency room. Results: We included 305 hospitalized patients, of whom 67 (22.0%) received tuberculosis treatment within the first 24 h after admission (≤24h group) and 238 (88.0%) did not (>24h group). Initiation of tuberculosis treatment within the first 24 h after admission was associated with being female (OR = 1.99; 95% CI: 1.06-3.74; p = 0.032) and with an AFB-positive spontaneous sputum smear (OR = 4.19; 95% CI: 1.94-9.00; p < 0.001). In the ≤24h and >24h groups, respectively, the ICU admission rate was 22.4% and 15.5% (p = 0.258); mechanical ventilation was used in 22.4% and 13.9% (p = 0.133); in-hospital mortality was 22.4% and 14.7% (p = 0.189); and a cure was achieved in 44.8% and 52.5% (p = 0.326). Conclusions: Although tuberculosis treatment was initiated promptly in a considerable proportion of the inpatients evaluated, the rates of in-hospital mortality, ICU admission, and mechanical ventilation use remained high. Strategies for the control of tuberculosis in primary care should consider that patients who seek medical attention at hospitals arrive too late and with advanced disease. It is therefore necessary to implement active surveillance measures in the community for earlier diagnosis and treatment.

Keywords: Tuberculosis; Hospitalization; Time-to-treatment; Emergency medicine; Delayed diagnosis.

Objective: To evaluate autonomic modulation in individuals with COPD, compared with healthy controls, via recurrence plots (RPs) and linear heart rate variability (HRV) indices. Methods: We analyzed data on 74 volunteers, who were divided into two groups: COPD (n = 43) and control (n = 31). For calculation of HRV indices, heart rate was measured beat-by-beat during 30 min of supine rest using a heart-rate meter. We analyzed linear indices in the time and frequency domains, as well as indices derived from the RPs. Results: In comparison with the control group, the COPD group showed significant increases in the indices derived from the RPs, as well as significant reductions in the linear indices in the time and frequency domains. No significant differences were observed in the linear indices in the frequency domains expressed in normalized units or in the low frequency/high frequency ratio. Conclusions: Individuals with COPD show a reduction in both sympathetic and parasympathetic activity, associated with decreased complexity of autonomic nervous system function, as identified by RPs, which provide important complementary information in the detection of autonomic changes in this population.

Keywords: Pulmonary disease, chronic obstructive; Autonomic nervous system; Nonlinear dynamics; Recurrence; Heart rate; Sympathetic nervous system.

Objective: To evaluate the treatment compliance of patients with paracoccidioidomycosis. Methods: We studied 188 patients with paracoccidioidomycosis admitted to a tertiary referral hospital in the Central-West Region of Brazil from 2000 to 2010, to assess their compliance to treatment. In order to be considered compliant, patients needed to present two established criteria: (1) receive medicines from the pharmacy, and (2) achieve a self-reported utilization of at least 80% of the dispensed antifungal compounds prescribed since their previous appointment. Results: Most patients were male (95.7%), had the chronic form of the disease (94.2%), and were treated with cotrimoxazole (86.2%). Only 44.6% of patients were treatment compliant. The highest loss to follow-up was observed in the first 4 months of treatment (p < 0.02). Treatment compliance was higher for patients with than for those without pulmonary involvement (OR: 2.986; 95%CI 1.351-6.599), and higher for patients with than without tuberculosis as co-morbidity (OR: 2.763; 95%CI 1.004-7.604). Conclusions: Compliance to paracoccidioidomycosis treatment was low, and the period with the highest loss to follow-up corresponds to the first four months. Pulmonary paracoccidioidal involvement or tuberculosis comorbidity predicts a higher compliance to paracoccidioidomycosis therapy.

Keywords: Paracoccidioidomycosis; Treatment adherence and compliance; loss to follow-up; mycoses

Objective: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis, which was recognized by the World Health Organization (WHO) as a global epidemic in 1993. TB is the leading infectious disease associated with silicosis, with studies showing an increased risk when compared to healthy individuals. We conducted an association study to evaluate the influence of polymorphisms in the ACE, FAM13A, FAS, FASLG, IL1RN, NOS2, TGFB1, and TNF genes on TB susceptibility. Methods: Nine polymorphisms were genotyped using Polymerase Chain Reaction (PCR) in a sample of 143 patients with silicosis in Rio de Janeiro (RJ), Brazil. Results: Seventy (49%) patients had a confirmed prior diagnosis of TB, of whom 25 (35.7%) had simple silicosis and 45 (64.3%) had complicated silicosis. The TG genotype of rs2609255 in FAM13A showed a protective effect against TB (OR=0.46; 95% CI: 0.22-0.98; p=0.040) compared to the GG genotype, and also when compared to the two combined homozygous genotypes (TT+GG) (OR=0.43; 95% CI: 0.20-0.90; p=0.024). Logistic regression analysis, including independent clinical variables, confirmed the protective effect of the TG genotype. Conclusion: This study suggests that the rs2609255 polymorphism in FAM13A may play a role in TB risk among patients with silicosis. Given the limited research on genetic polymorphisms and TB susceptibility in silicosis patients, further studies are needed to validate these findings.

Keywords: silicosis, tuberculosis, genetic polymorphisms, genetic association studies, cytokines.

Introduction: Bronchoscopy is useful in the diagnosis of tuberculosis suspects with a "negative" sputum smear. The objectives of this study were: to assess yield of bronchoalveolar lavage (BAL) and of transbronchial biopsy (TBB) both in HIV-positive patients (group 1) and immunocompetent individuals (group 2), based on simple and most available laboratory techniques in clinical practice. Patients and methods: The authors performed 319 bronchoscopies in 302 patients. BAL and TBB were sequentially performed in the same lung in all cases. Tuberculosis was diagnosed based on the results of acid-fast stains (AFS) from the lavage (ZN), culture for mycobacteria (LJ), and histological examination of biopsies (HE and ZN). Results: Tuberculosis was the final diagnosis in 28 exams of group 1 (n = 214) and in 35 of group 2 (n = 105). There were abnormal endoscopic findings respectively in 3 and 10 patients. In group 1, AFS were positive in 7 cases, culture of BAL in 14, and TBB in 19. In group 2, AFS were positive in 13 cases, culture in 17, and biopsies in 31. TBB results compared to BAL were in concordance for group 1 (p = 0.823) and different for group 2 (p = 0.022). Immediate results (AFS and TBB) compared to later positive results of culture were similar for group 1 (p = 0.066) but not for group 2 (p = 0.001). There were eight episodes of pneumothorax (2.5%) and one death (0.36%). Conclusions: Both BAL and TBB should be performed whenever possible, aiming towards a higher yield of bronchoscopy in the diagnosis of tuberculosis. Both methods complement each other in immunocompetent patients, whereas TBB establishes a faster diagnosis for HIV-infected patients if associated to AFS.

Keywords: Bronchoscopy/methods. Smear-negative tuberculosis/diagnosis. Opportunistic infections related to AIDS/diagnosis.

Objective: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. Methods: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. Results: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53‑6.65). Conclusions: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

Keywords: Lung neoplasms; Polymorphism, genetic; Metabolism.

Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

Keywords: Lung neoplasms; Chemotherapy, adjuvant; Cisplatin/toxicity; Vinorelbine/toxicity.

Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a ß2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Keywords: Polymorphism, genetic; Interleukin-10; Interleukin-17; Asthma.

Leflunomide is an anti-rheumatic drug with immunomodulating effects. Granulomatous interstitial pneumonia has never been described in association with the use of this drug. We report the case of a 33-year-old female patient who presented with chest pain, weight loss and pulmonary infectious syndrome during the fifth month of monotherapy with leflunomide for rheumatoid arthritis, which advanced to respiratory insufficiency in the sixth month. Radiologic findings revealed pulmonary intersticial infiltrates, as well as bilateral alveolar infiltrates (mainly in the upper and medium lobes) and scattered micronodules. However, no mediastinal abnormalities were detected. Leflunomide was suspended. After resolution of the infection, interstitial reticulonodular lesions persisted, predominantly in the upper 2/3 of the right lung and in the center of the left lung, interspersed with a ground-glass pattern in the superior lobes. Surprisingly, pulmonary biopsy revealed tuberculoid granulomas without caseous necrosis. A thorough etiological investigation was carried out, but no etiologic agent was identified. After four months, the condition spontaneously and completely disappeared. This profile suggests that the pulmonary complications seen in this case were the result of leflunomide use.

Keywords: Lung diseases, interstitial/chemically induced. Lung/drugs effects.

Objective: To describe the clinical and therapeutic aspects of pulmonary tuberculosis and compare the adverse effects of the treatment and its outcome in elderly and nonelderly patients. Methods: This was a case-control study of 117 elderly individuals (over the age of 60 years) and 464 nonelderly individuals (aged 15-49 years). All subjects presented pulmonary tuberculosis that had been diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 1980 and 1996. Results: In the elderly group, pulmonary tuberculosis was found to be correlated with diabetes (OR = 3.98; 95% CI = 2.07-7.65; p = 0.001), lung disease (OR = 7.24; 95% CI = 3.64‑14.46; p = 0.001) and heart disease (OR = 5.86; 95% CI = 2.88-11.95; p = 0.001). Smoking (OR = 2.07; 95% CI = 1.26‑3.42; p = 0.002) and alcohol abuse (OR = 1.63; 95% CI = 1.01-2.68; p = 0.041) were also more common in the elderly group. In the elderly group, the treatment more frequently resulted in adverse reactions (OR = 1.62; 95% CI = 1.04-2.54; p = 0.024), especially gastrointestinal reactions (OR = 1.64; 95% CI = 1.01-2.77; p = 0.047), and treatment efficacy was lower: cure rate, 51%; mortality rate, 24%. Treatment adherence was low (approximately 77%) in both groups. Conclusions: In the elderly group, adverse reactions were more common, treatment outcomes were less favorable, there was a greater frequency of clinical complications and deaths related to drug toxicity, and the prevalence of concomitant diseases was higher.

Keywords: Tuberculosis, pulmonary; Aged; Drug therapy; Treatment outcome.

Objective: To determine, based on international guidelines for asthma management, the appropriateness of the treatment that the Unified Health Care System provides to patients with asthma. Methods: This was a cross-sectional study involving patients suspected of having asthma and referred to the Pulmonology Clinic of the Federal University of Minas Gerais Hospital das Clínicas, Brazil, between November of 2006 and October of 2007. Results: A total of 102 patients were included, and 70 were diagnosed with asthma. The previous treatment was consistent with the guidelines in 18.6% of the patients; 50.0% of the patients had previously been submitted to spirometry, and 34.3% had previously been submitted to PEF. The most frequently prescribed medication was short-acting β2 agonists (90.3%). Conclusions: The results show that the majority of non-specialized physicians working within the public health care system do not manage the treatment of patients with asthma in accordance with the guidelines. This situation calls for continuing medical education programs that prioritize primary care.

Keywords: Asthma; Guideline adherence; Therapeutics; Public health.

Objective: To evaluate chest X-rays of patients with pulmonary tuberculosis and to determine whether the extent of radiographic lesions correlates with bacteriological parameters. Methods: In this retrospective, descriptive study, we evaluated chest X-rays, as well as AFB detection by smear microscopy and culture for Mycobacterium tuberculosis, initially and during the first two months of treatment, in 800 male patients hospitalized between 1995 and the present at a 250-bed hospital in northwestern Turkey. Results: The initial mean ESR was 58 ± 37 mm/h. Initial sputum smears and cultures were positive in 83.8% and 89.5% of the patients, respectively. After the first month of treatment, the proportion of patients with positive sputum culture was higher among those with cavitary tuberculosis than among those with non-cavitary tuberculosis (53.7% vs. 37.7%, p < 0.001). The number of affected zones was not correlated with age, symptom duration, contact with an active tuberculosis patient, or concomitant diabetes (p > 0.05 for all) but was positively correlated with the ESR (r = 0.23, p < 0.001). During the first and second months of treatment, conversion to smear-negative status was less common in patients with bilateral involvement than in those with unilateral involvement (p < 0.001 and p = 0.002 for months 1 and 2, respectively). Disease extent did not correlate with age, symptom duration, contact with an active tuberculosis patient, or concomitant diabetes but did correlate with delayed bacteriological recovery. Conclusions: Chest X-ray and bacteriology are valuable tools for the evaluation of pulmonary tuberculosis

Keywords: Radiography, thoracic; Bacteriology; Tuberculosis, pulmonary/drug therapy.

Objective: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. Methods: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. Results: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. Conclusions: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.

Keywords: Lung neoplasms; Age groups, Sex; Survival.

The role of immunohistochemistry is to recognize antigens and, consequently, to identify and classify specific cells within a cell population whose morphology is heterogenous or apparently homogenous. The visualization of the antigen-antibody complex is made possible through the addition of either a fluorochrome conjugate or an enzyme to the antibody, which is then viewed under microscopy. Immunohistochemistry can be used in the routine diagnosis of lung cancer, in order to identify biological markers (diagnostic and prognostic). The essential immunohistochemistry panels will be discussed in this review.

Keywords: Immunohistochemistry; Tumor markers, biological; Lung neoplasms.

Objective: To evaluate the results of thoracoscopy for the treatment of pleural empyema in pediatric patients. Methods: A retrospective study of 117 patients who underwent mediastinoscopy or video-assisted thoracoscopy for pleural empyema treatment. General anesthesia and single-lumen oral intubation were used. Surgery was indicated when there was pleural effusion and no clinical and radiological response to clinical treatment (antibiotics, physiotherapy and thoracocentesis) or severe sepsis, together with loculated pleural effusion (confirmed through ultrasound or computed tomography of the chest). Results: Between February of 1983 and July of 2006, 117 thoracoscopies were performed in patients ranging in age from 5 months to 17 years (mean, 4 years). Mean time for thoracic drainage was 9 days (range, 2-33 days), and mean period of hospitalization was 16.4 days (range, 4 to 49 days). One patient (0.8%) died after surgery, and persistent fistula was observed in 33 patients (28%). In 7 cases (6%), open thoracotomy with pulmonary decortication was performed due to the disposition of the empyema. Conclusions: Management of pleural empyema in this age bracket is still controversial, and surgical indication is often delayed, particularly when there are multiple loculations or severe sepsis. Early thoracoscopy yields a better clinical outcome for pediatric patients with pleural empyema, with apparent decreased morbidity and mortality, earlier chest tube removal, earlier hospital discharge and improved response to antibiotic therapy.

Keywords: Empyema, pleural; Pediatrics/instrumentation; Thoracoscopy; Thoracic surgery, video-assisted.

Background: Tuberculosis continues to be a global health problem. Objective: To evaluate an automated system designed to diagnose tuberculosis, comparing it to sputum microscopy and culture in Löwenstein-Jensen medium. Method: A comparative study using 844 sputum samples, collected between September and December of 1999 at a reference center for tuberculosis in São Paulo, Brazil, to draw distinctions between the results obtained through the use of the automated system and those obtained through sputum microscopy and culture in Löwenstein-Jensen medium. Results: Of the 844 samples evaluated, 27.1% tested positive for acid-fast bacilli, and 72.9% tested negative. In Löwenstein-Jensen culture, 34.7% were positive and 63% were negative, compared with 37.1% positivity and 56.9% negativity using the automated system. Sensitivity was 98.1% for the automated system and 91.9% for Löwenstein-Jensen culture. Specificity and positive predictive value were 100% for both methods. Negative predictive value was 98.9% for the automated system and 95.5% for Löwenstein-Jensen culture. The degree of accuracy was 99.3% for the automated system and 97% for Löwenstein-Jensen culture, and the Kappa was 0.99 for the automated system and 0.94 for Löwenstein-Jensen culture. The difference between the mean time to detection of mycobacteria using the automated system (10.5 days) and that found using Löwenstein-Jensen culture (34.7 days) was statistically significant. Conclusion: The difference between the culture yield obtained using the automated system and that achieved with Löwenstein-Jensen culture was statistically significant. Mean time to detection of mycobacteria was significantly shorter with the automated system. The higher yield provided by this new system justifies its use in a reference center for tuberculosis in São Paulo

Keywords: Mycobacterium tuberculosis. Diagnostic. Automated systems.