Objective: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in Brazil over the period 1979-2014. Methods: Microdata were extracted from the Brazilian National Ministry of Health Mortality Database. Only deaths for which the underlying cause was coded as International Classification of Diseases version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1 (from 1996 onward) were included in our analysis. Standardized mortality rates were calculated for the 2010 Brazilian population. The annual trend in mortality rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by age group, time period of death, and gender, using a person-years denominator. Results: A total of 32,092 deaths were recorded in the study period. Standardized mortality rates trended upward, rising from 0.24/100,000 population in 1979 to 1.10/100,000 population in 2014. The annual upward trend in mortality rates had two inflection points, in 1992 and 2008, separating three distinct time segments with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of RRs for the age groups, using the 50- to 54-year age group as a reference, and for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36) and 6.71 (6.34-7.12), respectively. Men compared with women had higher standardized mortality rates (per 100,000 person-years) in all age groups. Conclusion: Brazilian IPF mortality rates are lower than those of other countries, suggesting underdiagnosis or underreporting. The temporal trend is similar to those reported in the literature and is not explained solely by population aging.

Keywords: Idiopathic pulmonary fibrosis/epidemiology; Idiopathic pulmonary fibrosis/mortality; Population dynamics.

Objective: Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods: Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results: The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion: In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Keywords: Drug tolerance; Expanded access program; Interstitial lung disease; Tyrosine kinase inhibitor.

Epidemiologic data on idiopathic pulmonary fibrosis are relatively scarce, and its real incidence and prevalence are unknown. Recent studies suggest that idiopathic pulmonary fibrosis mortality is rising in developed countries. Objectives: To describe idiopathic pulmonary fibrosis mortality in the State of Rio Grande do Sul (RS), Brazil, from 1970 to 2000, analyzing its trend and comparing it with that from other countries. Methods: Prevalence study, using data from the Brazilian Institute of Geography and Statistics (IBGE), analyzing death certificates in which idiopathic pulmonary fibrosis was stated as ultimate cause of death. Results: Annual mortality adjusted to population was 0.22/100,000 persons in the 1970's, 0.3/100,000 persons in the 1980's, and 0.48/100,000 persons in the 1990's. Total mortality rised 36% from 1970 to 1980, and 70% from 1980 to 1990. Mortality adjusted to population rised 36% and 60% during the same periods. The rise in both total and adjusted mortality from IPF was statistically significant (p < 0.05). The mean mortality rate per 100,000 persons during 1996 to 1998, however, was 0.683, corresponding to a rise of 70% when compared to the previous three-year period, which was 0.4 (p = 0.0002), probably reflecting encoding practices. Conclusion: There was a significant increase in IPF mortality in RS from 1970 to 2000, in part due to changes in coding practices. This increase is in conformity with observations in other countries, althought mortality rates in RS are considerably lower.

Keywords: Pulmonary fibrosis. Mortality.

Objectives: To describe the temporal trend in and spatial distribution of mortality from tracheal, bronchial, and lung cancer in Brazil from 1979 to 2004. Methods: Mortality data by gender and geographic region were obtained from the Mortality Database created by the Ministry of Health in 1975. Demographic data were collected from the national censuses, from population counts, and from population estimates made in non-census years. Mortality rates were standardized according to the direct method, and the trends were analyzed by gender and geographic region using the Prais-Winsten method for generalized linear regression. Results: Lung cancer mortality accounted for approximately 12% of the overall neoplasia-related mortality during the period. There was a trend toward an increase for both genders and in all regions, except for the male population in the southeast region, whose rates remained steady between 1979 and 2004. The highest rates were observed in the south and southeast regions. However, the northeast region was the one that presented the greatest increase, followed by the central-west and north regions. In all regions, the increase in mortality rates was higher in women. Conclusions: The increase in lung cancer mortality in Brazil between 1979 and 2004 requires public measures that can minimize exposition to risk factors, mainly tobacco, and allow greater access to health care facilities for diagnosis and treatment.

Keywords: Lung neoplasms; Epidemiology; Brazil.

In order to evaluate which prognostic factors were significant to the survival of patients with idiopathic pulmonary fibrosis (IPF), 121 histologically confirmed cases of the disease were studied at the Pereira Filho Hospital from 1970 to 1996. All patients were submitted to a standard thorax X-ray and spirometry and answered a standardized questionnaire when admitted to hospital. They also underwent diffusion tests (34 cases), total lung capacity (28), blood gas analysis (106), bronchoalveolar lavage (39), rheumatoid analyses (45), and thoracic CT (24). For further analysis, the patients were classified into two groups: group A (2-year survival) with 55 patients, and group B (more than 5-year survival) with 24 patients; these features were also analyzed according to their significance to survival. Age, increased dyspnea index, long symptomatic period, FVC, DCO, PaO2 and SaO2 reduction, honeycombing intensity, and greater profusion of the reticular pattern on HRCT were considered indicative of worse prognosis. A reduced FEV1 and TLC were also associated with shorter survival. The use of those criteria which had shown statistical significance when evaluated together may determine a more accurate prognostic evaluation of IPF patients resulting in social and therapeutic benefits to patient management.

Keywords: Pulmonary fibrosis. Interstitial lung diseases. Prognosis. Prospective studies. Survival analysis.

Objective: To describe the clinical and functional findings recently reported in the medical literature for patients diagnosed with emphysema involving the upper lobes and idiopathic pulmonary fibrosis (IPF) involving the lower lobes. Methods: Eleven patients with emphysema and IPF were identified retrospectively. All of the patients underwent high-resolution computed tomography of the lung and pulmonary function tests. Results: Of the 11 patients, 8 were male and 3 were female. The mean age was 70.7 ± 7.2 years (range, 61-86 years). All of the patients were smokers (mean smoking history, 61.5 ± 43.5 pack-years). The mean values of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC were 72.1 ± 12.7%, 68.2 ± 11.9% and 74.4 ± 10.8, respectively. Lung volumes were normal in 7 patients. A restrictive pattern was observed in 3 patients, and hyperinflation was present in one. The diffusing capacity was moderatelyto- severely reduced in all of the patients (mean, 27.7% ± 12.9% of predicted). Ten of the 11 patients performed the six-minute walk test. The mean distance covered was 358.4 ± 143.1 m, and 9 of the 10 patients presented desaturation ≥ 4%. Echocardiographic findings suggestive of pulmonary hypertension were present in 4 patients (mean systolic pulmonary artery pressure, 61.8 mmHg; range, 36-84 mmHg). Conclusions: The concomitant presence of emphysema and IPF causes characteristic changes on pulmonary function tests. The most significant finding is a discrepancy between diffusing capacity and spirometry results.

Keywords: Pulmonary emphysema; Pulmonary fibrosis; Lung Diseases, interstitial; Anoxia; Hypertension, pulmonary.

Objective: To determine the cut-off point for the six-minute walk distance (6MWD) that indicates lower survival time in patients with idiopathic pulmonary fibrosis (IPF) in Brazil. Methods: This was retrospective study carried out in two referral centers for IPF. The 6MWT was performed twice, considering the highest value of the 6MWD. Various cut-off points were estimated, in absolute values and in percentage of predicted values, using ROC curves, the Kaplan-Meier method, and data from other studies. Results: The sample comprised 70 patients with IPF. The mean age was 71.9 ± 6.4 years, and 50 patients (71.4%) were male. The mean FVC was 76.6 ± 18.2% of predicted value. The mean SpO2 at rest before and after 6MWT were 93.8 ± 2.5% and 85.3 ± 6.5%, respectively. The median survival time was 44 months (95% CI: 37-51 months). The mean 6MWD was 381 ± 115 m (79.2 ± 24.0% of predicted). After the analyses, the best cut-off points for estimating survival were 6MWD < 330 m and < 70% of predicted. The median survival time of patients with a 6MWD < 330 m was 24 months (95% CI: 3-45 months), whereas that of those with a 6MWD ≥ 330 m was 59 months (95% CI: 41-77 months; p = 0.009). Similarly, the median survival times of those with a 6MWD < 70% and ≥ 70% of predicted, respectively, were 24 months (95% CI: 13-35 months) and 59 months (95% CI: 38-80 months; p = 0.013). Cox multivariate regression models including age, sex, smoking status, SpO2 at the end of the 6MWT, and FVC% showed that 6MWD remained significantly associated with survival (p = 0.003). Conclusions: Values of 6MWD < 330 m and < 70% of predicted value were associated with lower survival time in IPF patients in Brazil.

Keywords: Lung diseases, interstitial; Pulmonary fibrosis; Exercise tolerance.

Objectives: To determine the trend of self-reported asthma diagnosed prevalence and to describe the factors associated with asthma in Brazilian adults. Method: Epidemiological cross-sectional study based on databases analysis from three national household surveys: Pesquisa Nacional por Amostra de Domicílios (PNAD) 2003, PNAD 2008 and Pesquisa Nacional de Saúde (PNS) 2013. Participants between 18-45 years old were included. Trend analysis of asthma diagnosed prevalence was conducted using a logistic general linear model. A hierarchical logistic regression model was used to select factors significantly associated with asthma prevalence. Results: Asthma diagnosed prevalence was 3.6% (2003), 3.7% (2008) and 4.5% (2013), showing a statistically significant increased trend. Asthma diagnosed prevalence also increased when analysed by gender (annual change for men: 2.47%, p < 0.003; women: 2.16%, p < 0.001), urban area (annual change for urban: 2.15%, p < 0.001; rural: 2.69%, p = 0.072), healthcare insurance status (annual change without healthcare insurance: 2.18%, p < 0.001; with healthcare insurance: 1.84%, p = 0.014), and geographic regions (annual change North: 4.68%, p < 0.001; Northeast: 4.14%, p < 0.001; and Southeast: 1.84%, p = 0.025). Female gender, obesity, living in urban areas and depression were associated with asthma diagnosed prevalence. Discussion: PNAD and PNS surveys allow for a very large, representative community-based sample of the Brazilian adults to investigate the asthma prevalence. From 2003 to 2013, the prevalence of self-reported physician diagnosis of asthma increased, especially in the North and Northeast regions. Gender, region of residence, household location (urban/rural), obesity, and depression diagnosis seem to play significant roles in the epidemiology of asthma in Brazil.

Keywords: Adults; Asthma; Logistic models; Prevalence; Risk factors.

Objective: To characterize deaths from pulmonary tuberculosis, according to sociodemographic and operational variables, in the city of São Luís, Brazil, and to describe their spatial distribution. Methods: This was an exploratory ecological study based on secondary data from death certificates, obtained from the Brazilian Mortality Database, related to deaths from pulmonary tuberculosis. We included all deaths attributed to pulmonary tuberculosis that occurred in the urban area of São Luís between 2008 and 2012. We performed univariate and bivariate analyses of the sociodemographic and operational variables of the deaths investigated, as well as evaluating the spatial distribution of the events by kernel density estimation. Results: During the study period, there were 193 deaths from pulmonary tuberculosis in São Luís. The median age of the affected individuals was 52 years. Of the 193 individuals who died, 142 (73.60%) were male, 133 (68.91%) were Mulatto, 102 (53.13%) were single, and 64 (33.16%) had completed middle school. There was a significant positive association between not having received medical care prior to death and an autopsy having been performed (p = 0.001). A thematic map by density of points showed that the spatial distribution of those deaths was heterogeneous and that the density was as high as 8.12 deaths/km2. Conclusions: The sociodemographic and operational characteristics of the deaths from pulmonary tuberculosis evaluated in this study, as well as the identification of priority areas for control and surveillance of the disease, could promote public health policies aimed at reducing health inequities, allowing the optimization of resources, as well as informing decisions regarding the selection of strategies and specific interventions targeting the most vulnerable populations.

Keywords: Tuberculosis, pulmonary/mortality; Communicable disease control; Spatial analysis.

The objective of this study was to analyze trends in the tuberculosis mortality rate in Brazil (1990-2015) in an ecological time-series analysis. The indicators were obtained from the Brazilian National Ministry of Health. A joinpoint regression model was applied for the temporal analysis, with a level of significance of 5%. During the period in question, there was a trend toward a reduction in mortality in the country as a whole (p < 0.001) and in each of its five regions. The states with the highest tuberculosis mortality rates were Rio de Janeiro (7.0/100,000 population) and Pernambuco (5.0/100,000 population). Eleven states and the Federal District of Brasília showed downward trends. Only the state of Alagoas showed a significant increase (p < 0.001). The temporal behavior observed indicates that tuberculosis continues to be a major public health problem in Brazil.

Keywords: Tuberculosis/epidemiology; Tuberculosis/mortality; Mortality/trends; Epidemiologic studies.

The objective of this study was to describe temporal trends in tuberculosis morbidity and mortality in the state of Santa Catarina, Brazil, between 2002 and 2009. Data regarding mortality and incidence were obtained from the Brazilian Mortality Database and National Case Registry Database, respectively. Crude rates were calculated and standardized by age using the direct method. We estimated annual variation by joinpoint regression, identifying the points at which there were changes in the trends. There was a significant (3.7%) annual decrease in the mortality rate. In the study period, two distinct temporal trends were identified: one between 2002 and 2007, showing a significant (5.9%) annual decrease in the mortality rate; and one between 2007 and 2009, showing an insignificant (2.0%) annual increase. There was also a significant (0.9%) annual reduction in tuberculosis incidence.

Keywords: Tuberculosis/epidemiology; Tuberculosis/mortality; Brazil.

Background: Idiopathic pulmonary fibrosis was recently redefined as usual interstitial pneumonia of unknown etiology. Consequently, the prognostic value of histological findings needs to be reassessed. Objective: To correlate clinical, functional and histological findings with survival in patients with idiopathic pulmonary fibrosis. Method: Patients (n = 51; mean age: 66 ± 8 years; gender: 21 females/30 males) were evaluated. Of the 51, 26 were smokers or ex-smokers. Duration of symptoms, forced vital capacity and smoking habits were recorded. All patients presented usual interstitial pneumonia verified through histology. Degree of honeycombing, established fibrosis, desquamation, cellularity, myointimal thickening of blood vessels and number of fibroblastic foci were graded according to the semiquantitative method. Results: Median duration of symptoms was 12 months and initial forced vital capacity was 72 ± 21%. Cox multivariate analysis revealed that survival correlated inversely and significantly (p < 0.05) with duration of symptoms and fibroblastic foci score, as well as with myointimal thickening of blood vessels. Limited numbers of fibroblastic foci, as well as myointimal thickening involving less than 50% of blood vessels, were predictive of greater survival. No correlation with survival was found for gender, age, forced vital capacity, inflammation or degree of cellularity. Conclusion: Semiquantitative analysis of lung biopsies yields relevant prognostic information regarding patients with usual interstitial pneumonia.

Keywords: Pulmonary fibrosis. Lung diseases, interstitial. Survival analysis.

Objective: To determine the spatial distribution of tuberculosis in the city of Ribeirão Preto, located in the state of São Paulo, Brazil, between 1998 and 2002, with a focus on the potential spatially-dependent nature of its occurrence. Methods: The secondary Epi-Tb database of the Ribeirão Preto Municipal Secretary of Health. Georeferencing of tuberculosis cases was performed using MapInfo 6.5 software, and the Spring program was used for statistical analysis of spatial data. Results: Through analysis of the existing spatial pattern and those of the previous years analyzed, we found a consistent pattern of spatial distribution of tuberculosis in Ribeirão Preto. Although there are areas that were homogeneous in terms of risk, the highest concentrations of cases were found in one zone, consisting of middle- to lower middle-class neighborhoods, located in the northeast part of the city. Conclusion: These results add to the store of knowledge regarding the spatial distribution of tuberculosis in Ribeirão Preto in various periods, emphasizing the importance of space as a methodological alternative to aid the planning, monitoring and evaluation of health care programs, allowing interventions to be more appropriately directed in order to decrease inequalities in the allocation of health care resources.

Keywords: Tuberculosis/epidemiology; Health status indicators; Residence characteristics; Urban health/ statistics & numerical data; Topography, medical

Objective: To identify mycobacterial species in the sputum of patients suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. Methods: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smear microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65) to identify the strains of mycobacteria isolated in culture. Results: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM) in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. Conclusions: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria. Keywords:

Keywords: Tuberculosis; Mycobacteria, atypical; Polymerase chain reaction; Brazil.

Objective: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. Methods: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Results: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Conclusions: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished.

Keywords: Tuberculosis/epidemiology; HIV infections/epidemiology; Comorbidity.