Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by inhalation of silica particles. Genetic factors might play a role in the severity silicosis. We sought to evaluate the influence of polymorphisms in the ACE, FAS, FASLG, NOS2, IL1RN, FAM13A, TGFB1, and TNF genes on the severity of silicosis. Methods: Nine polymorphisms were genotyped by PCR in a sample of 143 patients with silicosis in the state of Rio de Janeiro, Brazil. Results: Fifty-seven patients (40%) were classified as having simple silicosis and 86 (60%) were classified as having complicated silicosis. The TT genotype of rs1800469 in the TGFB1 gene showed a protective effect for complicated silicosis (OR = 0.35; 95% CI, 0.14-0.92; p = 0.028) when compared with the other two genotypes (CC+CT). The polymorphic T allele of rs763110 in the FASLG gene (OR = 0.56; 95% CI, 0.31-0.99; p = 0.047), as well as a dominant model for the T allele (TT+CT: OR = 0.37; 95% CI, 0.15-0.96; p = 0.037), also showed a protective effect. When patients with simple silicosis despite having been exposed to silica for a longer time (> 44,229 hours) were compared with patients with complicated silicosis despite having been exposed to silica for a shorter time, the T allele of rs763110 in the FASLG gene (OR = 0.20; 95% CI, 0.08-0.48; p < 0.0001), as well as dominant and recessive models (OR = 0.06; 95% CI, 0.00-0.49; p = 0.01 and OR = 0.22; 95% CI, 0.06-0.77; p = 0.014, respectively), showed a protective effect against the severity of silicosis. Conclusions: It appears that rs1800469 polymorphisms in the TGFB1 gene and rs763110 polymorphisms in the FASLG gene are involved in the severity of silicosis. Given the lack of studies relating genetic polymorphisms to the severity of silicosis, these results should be replicated in other populations.

Keywords: Silicosis; Polymorphism, genetic; Genetic association studies; Cytokines.

Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes. We aimed to determine whether telomere length (TL) correlates with silicosis or severity of silicosis in silica-exposed workers in Brazil. Methods: We included 200 men in southeastern Brazil: 100 with silicosis and 100 who had not been exposed to silica. We extracted DNA from buccal cells and assessed TL by multiplex quantitative polymerase chain reaction. Results: The median TL was significantly shorter in the patients with silicosis than in the unexposed controls (p < 0.0001), although it did not differ between the patients with simple silicosis and those with complicated silicosis (p = 0.961). We also found that, in patients with silicosis, TL was influenced by smoking (p = 0.034) and by a history of personal protective equipment use in the workplace (p = 0.002). Conclusions: Silica exposure appears to have an impact on TL, which was found to be shorter in patients with silicosis than in unexposed controls. Further studies are needed in order to confirm the impact that oxidative stress caused by silica inhalation has on telomeres.

Keywords: Silicosis; Oxidative stress; Inflammation; Telomere.

Background: The primary work-related lung disease in Brazil is silicosis. Its pathogenic agent is the dust of crystalline free silica (SiO2; silicon dioxide). The inflammatory process of silicosis is not yet well understood. Objective: To analyze, through immunologic laboratory evaluation, including nonspecific and specific immunity, the profile of IgG, IgM, IgA, C3, C4 and autoantibodies in the serum of workers, with or without silicosis, exposed to silica. Methods: Fifty-eight male workers were studied. All had been exposed to silica. Immunologic, radiologic and functional evaluations were made. The immunoglobulins IgG, IgA, and IgM, the complement system components C3 and C4, and the autoantibodies were assessed. Results: Chest X-rays were normal in 20 of the 58 workers and compatible with silicosis in 38. Among the 38 who were positive, IgG values were, on average, higher than in the group with normal X-rays (p < 0.05). There were no significant differences in average values of IgA, IgM, C3 or C4 (p > 0.05). The percentage of autoantibody positivity was higher in the silicosis group than in the group with normal X-rays. Conclusion: The increased levels of IgG in patients with silicosis constitutes an important discovery. It may represent continuity of the granulomatous reaction, even when the individual is no longer being exposed to silica. However, further studies are necessary in order to increase understanding of the mechanism involved in the silicosis immunologic process.

Keywords: Lung diseases. Silicosis. Occupational diseases. Immunoglobulins

Silica is one of the main occupational agents associated with lung cancer. It is classified by the International Agency for Research on Cancer (IARC) as a Group 1 substance, i.e., carcinogenic for humans, since 1996. The objective of this paper is to report two cases of workers previously exposed to silica who developed lung cancer, seen in an out-patient clinic, focusing on important points of the current literature on the subject.

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: Silicosis is the most prevalent pneumoconiosis in Brazil, with most of the registered cases occurring in the State of Minas Gerais. Although it is a preventable disease, silicosis is still epidemic in some areas. Objective: To describe the profile of workers seen at the Clinics Hospital of the Federal University of Minas Gerais. Patients and methods: 300 medical records of silica-exposed workers in different occupations, seen between 1989-2000, were reviewed. Clinical and occupational information, radiographic and spirometric data were analyzed. Statistical methods included univariate analyses with chi-square and t tests. Results and conclusion: The mean age of the exposed patients was 51 years, with mean exposure duration of 15.6 years. 126/300 (42%) were radiologically classified as cases of silicosis. Increasing grades of profusion were associated with lower spirometric indices and more frequent associations with tuberculosis and chronic airflow limitation. Most of the workers were regularly registered employees and the main occupational activity was mining, accounting for the exposure of 197 (66%) workers. Non-registered workers presented more severe radiological grades of silicosis, suggesting, possibly, worse conditions of silica exposure in this group of workers.

Objective: To identify associations between genetic polymorphisms (in the MBL2, TGF-β1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of ΔF508 alleles and lung disease severity in such patients. Methods: This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-β1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-β1 genes at codon 10, position +869, were genotyped using the allele-specific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion. Results: Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-β1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity. Conclusions: There was an association between the TC genotype of the T869C polymorphism (TGF-β1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a ΔF508 homozygote and presenting severe lung disease.

Keywords: Cystic fibrosis; Polymorphism, genetic; Severity of illness index; Mannose-binding lectin; Transforming growth factor beta.

Objective: To determine the prevalence and duration of social security benefit (SSB) claims granted to registered workers with asthma in Brazil by the Brazilian National Institute of Social Security in 2008. Methods: This was a retrospective, descriptive study, based on information obtained from the Brazilian Unified Benefit System database, on the number of SSB claims granted to registered workers with asthma in 2008. The reference population was the monthly mean number of workers registered in the Brazilian Social Registry Database in 2008. The variables studied were type of economic activity, gender, age, and type/duration of the SSB allowance. The relationship between work and asthma was evaluated by the prevalence ratio (PR) between work-related and non-work-related SSB claims for asthma. Results: In 2008, 2,483 SSB claims were granted for asthma, with a prevalence of 7.5 claims per 100,000 registered workers. The prevalence was higher among females than among males (PR = 2.1 between the sexes). Workers  40 years of age were 2.5 times more likely to be granted an SSB allowance for asthma than were younger workers. The prevalence was highest among workers engaged in the following types of economic activity: sewage, wood and wood product manufacturing, and furniture manufacturing (78.8, 22.4, and 22.2 claims/100,000 registered workers, respectively). The median (interquartile range) duration of SSB claims for asthma was 49 (28-87) days. Conclusions: Asthma is a major cause of sick leave, and its etiology has a strong occupational component. This has a major impact on employers, employees, and the social security system. Being female, being  40 years of age, and working in the areas of sewage, wood and wood product manufacturing, and furniture manufacturing increase the chance of sick leave due to asthma.

Keywords: Asthma; Social security; Prevalence; Occupational exposure; Occupational health.

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.

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

Keywords: Occupational diseases; Mesothelioma; Genes, tumor suppressor; Oncogenes; Signal transduction.

Silicosis among pit diggers was first described in 1984. Two years later, a focus of the disease was detected in the region of Ibiapaba, State of Ceará, Brazil. The aims of this study were: 1) to present the educational program to which these workers and their families were submitted; 2) to study, in this population, the impact of the educational program on the knowledge about silicosis and on the behavior changes in the pit digging activity. First, a primary preventing educational intervention (PPEI) was created as per the critical awareness-raising method by Paulo Freire, and applied to this population. Subsequently, the role of PPEI on silicosis control among the pit diggers was studied. In the region there were 1202 pit diggers, and 687 from 5 selected towns were submitted to PPEI. Out of these, 287 workers participated of the second part of the study. All of them were male, ages from 18 to 78 years, 115 were silicotic, 122 non-silicotic, and 46 did not know their health status. Results show that PPEI brought to silicotic and non-silicotic workers a deep knowledge about the relationship between pit digging and silicosis, and induced most of them (85.8%) to quit this activity. PPEI itself promoted an awareness of this population about silicosis, interrupting the epidemiological cycle of the disease in the region of Ibiapaba.

Keywords: Silicosis. Epidemiology. Occupational lung diseases.

Objectives: To characterize the main identified mutations on cystic fibrosis transmembrane conductance regulator (CFTR) in a group of children and adolescents at a cystic fibrosis center and its association with the clinical and laboratorial characteristics. Method: Descriptive cross-sectional study including patients with cystic fibrosis who had two alleles identified with CFTR mutation. Clinical, anthropometrical, laboratorial and pulmonary function (spirometry) data were collected from patients' records in charts and described with the results of the sample genotyping. Results: 42 patients with cystic fibrosis were included in the study. The most frequent mutation was F508del, covering 60 alleles (71.4%). The second most common mutation was G542X (six alleles, 7.1%), followed by N1303K and R1162X mutations (both with four alleles each). Three patients (7.14%) presented type III and IV mutations, and 22 patients (52.38%) presented homozygous mutation for F508del. Thirty three patients (78.6%) suffered of pancreatic insufficiency, 26.2% presented meconium ileus, and 16.7%, nutritional deficit. Of the patients in the study, 59.52% would be potential candidates for the use of CFTR-modulating drugs. Conclusions: The mutations of CFTR identified more frequently were F508del and G542X. These are type II and I mutations, respectively. Along with type III, they present a more severe cystic fibrosis phenotype. More than half of the sample (52.38%) presented homozygous mutation for F508del, that is, patients who could be treated with Lumacaftor/Ivacaftor. Approximately 7% of the patients (7.14%) presented type III and IV mutations, therefore becoming candidates for the treatment with Ivacaftor.

Keywords: Cystic fibrosis; Mutations; Genetics; Phenotype; Child

Objective: To describe the sociodemographic and clinical characteristics of individuals exposed to smoking or biomass smoke and followed at primary health care (PHC) centers across three states in Brazil. Methods: This was a cross-sectional multicenter study including patients followed at any of four PHC centers in Brazil. Patients = 35 years of age who were smokers or former smokers, or were exposed to biomass smoke were included, the exception being those with physical/mental disabilities and those who were pregnant. Face-to-face assessments included a questionnaire assessing clinical and sociodemographic characteristics, as well as the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) dyspnea scale. Results: Of a total of 737 patients, 56.3% were female and 64.2% were White, with a mean age of 57.7 ± 11.8 years. Most (54.4%) had < 9 years of schooling, 50.2% had low socioeconomic status, and 71.5% were overweight/obese. Smokers accounted for 43.4% of the study sample, whereas 15.0% had no direct exposure to cigarette smoke. Common symptoms included cough, in 37.3%; wheezing, in 33.8%; and phlegm, in 27.4%. Most (75.1%) of the study participants had mMRC dyspnea scale scores of 0 or 1. CAT scores were 0-10, in 40.2%; 11-20, in 44.6%; 21-30, in 14.1%; and 31-40, in 1.1%. Binary logistic regression showed that sex and age significantly impacted mMRC dyspnea scale predictions, whereas BMI and socioeconomic status influenced CAT predictions. Common comorbidities included hypertension, in 51.3%; depression, in 27.4%; and diabetes, in 24.3%. No association was found between hypertension and obesity or smoking, or between diabetes and obesity or smoking. Conclusions: PHC patients with risk factors such as smoking and exposure to biomass smoke have a high comorbidity burden, with over half experiencing mild to moderate quality-of-life impacts. This study emphasizes the need for targeted preventive measures in PHC settings.

Keywords: Smoking; Risk factors; Biomass; Primary health care.

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.

Objective: To determine the prevalence of respiratory symptoms and smoking, as well as pulmonary function parameters among charcoal production workers in three cities in southern Brazil. Methods: This was an observational study including 67 individuals. Data were obtained by means of interviews and spirometry. Results: Of the 67 workers, 50 (75.0%) were male; mean age, 46.52 ± 13.25 years; mean BMI, 25.7 ± 3.85 kg/m2; FEV1, 3.24 ± 0.82 L (93.2 ± 16.0% of predicted); FVC, 4.02 ± 0.92 L (95.5 ± 14.3% of predicted); and FEV1/FVC, 80.31 ± 9.82. The most common upper airway symptoms were sneezing and nasal secretion-in 24 workers (35.82%)-whereas the most common lower airway symptom was cough-in 15 (22.38%). Of the 67 workers, 21 (31.34%) were smokers. In comparison with the nonsmokers, the smokers more often presented with cough (OR = 5.00; p = 0.01), nasal obstruction (OR = 3.50; p = 0.03), nasal itching (OR = 8.80; p = 0.01) and wheezing (OR = 10.0; p = 0.03), as well as presenting with lower FEV1 values (2.93 ± 0.80 vs. 3.38 ± 0.80 L; p = 0.04). We detected occupational rhinitis in 14 workers (20.85%), asthma in 4 (5.97%) and COPD in 4 (5.97%). Conclusions: Respiratory symptoms and airflow reduction were more common in the smoking workers. Controlling the progression of the pyrolysis did not increase the prevalence of respiratory symptoms in the charcoal production workers studied.

Keywords: Air pollution; Spirometry; Charcoal.

Background: Asthma is considered the most common chronic childhood disease. However, there have been few studies on the prevalence of asthma in Brazil. Objective: To assess the prevalence and severity of asthma symptoms in school-age children and adolescents living in the city of Duque de Caxias, located in the greater metropolitan area of Rio de Janeiro. Method: Cross-sectional transversal study using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The sample comprised students of 6, 7, 13 and 14 years of age. Results: One group of 2334 students between the ages of 6 and 7 and another composed of 4040 students between the ages of 13 and 14 were evaluated. The prevalence of wheezing within the last 12 months in the younger children was 27.7%, vs. 19% among the adolescents (p < 0.0001). There was a predominance of males in the 6-7 age group (29.9% vs. 25.6%; p = 0.01) and of females in the 13-14 age group (21.9% vs. 15.8%; p < 0.0001). The proportion of previously diagnosed cases of asthma was similar (approximately 10%) for both age brackets. Wheezing upon physical exertion was more prevalent among the adolescents (21.4% vs. 7.8%; p < 0.0001). Symptom severity was higher among female adolescents (severe asthma: 6.6% vs. 4.4%; p = 0.001), although no differences among genders were seen in the 6-7 age group. Conclusion: Asthma prevalence in Duque de Caxias is high, as it is in other Brazilian and Latin American cities. Values are higher in the 6-7 age group, in which symptoms were seen predominantly in males. Among the adolescents, the prevalence and severity of symptoms were higher in females, a recent observation that seems to be a new epidemiological trend of asthma.

Keywords: Key words: Asthma. Epidemiology. Severity of illness index. Cross-sectional studies.

Objective: To evaluate the association between the risk of death from COPD and air temperature events in ten major Brazilian microregions. Methods: This was a time series analysis of daily COPD deaths and daily mean air temperatures between 1996 and 2017. Using distributed nonlinear lag models, we estimated the cumulative relative risks of COPD mortality for four temperature percentiles (representing moderate and extreme cold and heat events) in relation to a minimum mortality temperature, with a lag of 21 days, in each microregion. Results: Significant associations were found between extreme air temperature events and the risk of death from COPD in the southern and southeastern microregions in Brazil. There was an association of extreme cold and an increased mortality risk in the following microregions: 36% (95% CI, 1.12-1.65), in Porto Alegre; 27% (95% CI, 1.03-1.58), in Curitiba; and 34% (95% CI, 1.19-1.52), in São Paulo; whereas moderate cold was associated with an increased risk of 20% (95% CI, 1.01-1.41), 33% (95% CI, 1.09-1.62), and 24% (95% CI, 1.12-1.38) in the same microregions, respectively. There was an increased COPD mortality risk in the São Paulo and Rio de Janeiro microregions: 17% (95% CI, 1.05-1.31) and 12% (95% CI, 1,02-1,23), respectively, due to moderate heat, and 23% (95% CI, 1,09-1,38) and 32% (95% CI, 1,15-1,50) due to extreme heat. Conclusions: Non-optimal air temperature events were associated with an increased risk of death from COPD in tropical and subtropical areas of Brazil.

Keywords: Pulmonary disease, chronic obstructive/mortality; Temperature; Climate.