Marcelo Fouad Rabahi

III Diretrizes para Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

New scientific articles about tuberculosis (TB) are published daily worldwide. However, it is difficult for health care workers, overloaded with work, to stay abreast of the latest research findings and to discern which information can and should be used in their daily practice on assisting TB patients. The purpose of the III Brazilian Thoracic Association (BTA) Guidelines on TB is to critically review the most recent national and international scientific information on TB, presenting an updated text with the most current and useful tools against TB to health care workers in our country. The III BTA Guidelines on TB have been developed by the BTA Committee on TB and the TB Work Group, based on the text of the II BTA Guidelines on TB (2004). We reviewed the following databases: LILACS (SciELO) and PubMed (Medline). The level of evidence of the cited articles was determined, and 24 recommendations on TB have been evaluated, discussed by all of the members of the BTA Committee on TB and of the TB Work Group, and highlighted. The first version of the present Guidelines was posted on the BTA website and was available for public consultation for three weeks. Comments and critiques were evaluated. The level of scientific evidence of each reference was evaluated before its acceptance for use in the final text.

Noncompliance with tuberculosis treatment by patients at a tuberculosis and AIDS reference hospital in midwestern Brazil

INTRODUCTION In developing countries, there is little information about the risk factors that predict noncompliance with tuberculosis (TB) treatment in hospitals. OBJECTIVE This study analyzes possible factors associated with noncompliance with TB treatment among patients treated at HAA. DESIGN A retrospective cohort study was made including all patients who initiated TB treatment at HAA, from January to December 1998. A standard form was used to review medical records and to collect data on each patient. This data was evaluated in comparison with data from the state TB control program. RESULTS Of the 341 patients included in the study, 186 (61.2%) were considered cured and 67 (22%) were non-compliant. The factors associated with noncompliance were: previous anti-TB treatment (RR = 1.95, 95% CI 1.29 to 2.93), prescription of drugs other than the standard first-line regimen proposed by the Brazilian Health Ministry (Rifampin + Isoniazide + Pyrazinamide) (RR = 0.54, 95% CI 0.35 to 0.83), the need for hospitalization (RR = 2.19, 95% CI 1.46 to 3.29) and non-inclusion in the hospital s TB Control Program for treatment follow up (RR = 0.54, 95% CI 0.35 to 0.82). SETTING Anuar Auad Hospital (HAA) Goiânia, Goiás, Brazil. CONCLUSION Our results indicate the importance of establishing Tuberculosis Control Programs in hospitals, while paying special attention to patients with risk factors for noncompliance with TB treatment.

Humoral response to HspX and GlcB to previous and recent infection by Mycobacterium tuberculosis

BackgroundTuberculosis (TB) remains a major world health problem. Around 2 billions of people are infected by Mycobacterium tuberculosis, the causal agent of this disease. This fact accounts for a third of the total world population and it is expected that 9 million people will become infected each year. Only approximately 10% of the infected people will develop disease. However, health care workers (HCW) are continually exposed to the bacilli at endemic sites presenting increased chance of becoming sick. The objective of this work was to identify LTBI (latent tuberculosis infection) among all asymptomatic HCW of a Brazilian Central Hospital, in a three year follow up, and evaluate the humoral response among HCW with previous and recent LTBI to recombinant HspX and GlcB from M. tuberculosis.MethodsFour hundred and thirty seven HCW were screened and classified into three different groups according to tuberculin skin test (TST) status: uninfected, previous LTBI and recent LTBI. ELISA test were performed to determine the humoral immune response to HspX and GlcB.ResultsThe levels of IgG and IgM against the HspX and GlcB antigens were the same among HCW with recent and previous LTBI, as well as among non infected HCW. However, the IgM levels to HspX was significantly higher among HCW with recent LTBI (OD = 1.52 ± 0.40) than among the uninfected (OD = 1.09 ± 0.50) or subjects with previous LTBI (OD = 0.96 ± 0.51) (p < 0.001).ConclusionIgG and IgM humoral responses to GlcB antigens were similar amongst all studied groups; nevertheless IgM levels against HspX were higher among the recent LTBI/HCW.

Subdiagnóstico de DPOC na atenção primária em Aparecida de Goiânia, Goiás

OBJECTIVE: To estimate the prevalence of undiagnosed COPD among individuals with risk factors for the disease treated at primary health care clinics (PHCCs) in the city of Aparecida de Goiânia, Brazil. METHODS: Inclusion criteria were being > 40 years of age, having a > 20 pack-year history of smoking or a > 80 hour-year history of exposure to biomass smoke, and seeking medical attention at one of the selected PHCCs. All subjects included in the study underwent spirometry for the diagnosis of COPD. RESULTS: We successfully evaluated 200 individuals, mostly males. The mean age was 65.9 ± 10.5 years. The diagnosis of COPD was confirmed in 63 individuals, only 18 of whom had been previously diagnosed with COPD (underdiagnosis rate, 71.4%). There were no significant differences between the subgroups with and without a previous diagnosis of COPD in relation to demographics and risk factors. However, there were significant differences between these subgroups for the presence of expectoration, wheezing, and dyspnea (p = 0.047; p = 0.005; and p = 0.047, respectively). The FEV1 and FEV1/FVC ratio, expressed as percentages of the predicted values, were significantly lower in the subjects with a previous diagnosis of COPD, which was predominantly mild or moderate in both subgroups. CONCLUSIONS: The rate of underdiagnosis of COPD was high at the PHCCs studied. One third of the patients with risk factors for COPD met the clinical and functional criteria for the disease. It seems that spirometry is underutilized at such facilities.

Interleukin-6 and interleukin-8 blood levels’ poor association with the severity and clinical profile of ex-smokers with COPD

Background The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology. This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD. Methods and findings Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls. The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden. COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group. Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m2, with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis. The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year. Conclusion Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype. No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers.

Sequence analysis of NAT2 gene in Brazilians: identification of undescribed single nucleotide polymorphisms and molecular modeling of the N-acetyltransferase 2 protein structure

N-Acetyltransferase 2 (NAT2) metabolizes a variety of xenobiotics that includes many drugs, chemicals and carcinogens. This enzyme is genetically variable in human populations and polymorphisms in the NAT2 gene have been associated with drug toxicity and efficacy as well as cancer susceptibility. Here, we have focused on the identification of NAT2 variants in Brazilian individuals from two different regions, Rio de Janeiro and Goiás, by direct sequencing, and on the characterization of new haplotypes after cloning and re-sequencing. Upon analysis of DNA samples from 404 individuals, six new SNPs (c.29T>C, c.152G>T, c.203G>A, c.228C>T, c.458C>T and c.600A>G) and seven new NAT2 alleles were identified with different frequencies in Rio de Janeiro and Goiás. All new SNPs were found as singletons (observed only once in 808 genes) and were confirmed by three independent technical replicates. Molecular modeling and structural analysis suggested that p.Gly51Val variant may have an important effect on substrate recognition by NAT2. We also observed that amino acid change p.Cys68Tyr would affect acetylating activity due to the resulting geometric restrictions and incompatibility of the functional group in the Tyr side chain with the admitted chemical mechanism for catalysis by NATs. Moreover, other variants, such like p.Thr153Ile, p.Thr193Met, p.Pro228Leu and p.Val280Met, may lead to the presence of hydrophobic residues on NAT2 surface involved in protein aggregation and/or targeted degradation. Finally, the new alleles NAT2*6H and NAT2*5N, which showed the highest frequency in the Brazilian populations considered in this study, may code for a slow activity. Functional studies are needed to clarify the mechanisms by which new SNPs interfere with acetylation.

Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia

OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health-rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months-involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (≥ 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. RESULTS: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. CONCLUSIONS: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous basic regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

Health care workers humoral immune response against GLcB, MPT51 and HSPX from Mycobacterium tuberculosis

Tuberculosis (TB) is one of the oldest human infectious diseases and one third of the worlds population is latently infected. Brazil is an endemic area for TB. One of the most important challenges in TB control is the identification of latently infected individuals. Health Care Workers (HCW) are at high risk of being infected with Mycobacterium tuberculosis and even to become TB latently infected. The aim of this study was to increase knowledge about humoral immune response in TB latently infected individuals. HCW were classified according to their tuberculin skin test (TST), as positive or negative. The antibody response to GLcB, MPT51 and HSPX from Mycobacterium tuberculosis was evaluated. TST negative HCW constituted the majority of those who showed a humoral immune response. Antibody levels varied according to antigen characteristics, TST and BCG status. We suggest that possibly the presence of those antibodies could have a function in the protective immune response against Mycobacterium tuberculosis.

Achados de fibrobroncoscopia em pacientes com diagnóstico de neoplasia pulmonar

OBJECTIVE: To compile fiberoptic bronchoscopy findings in patients diagnosed with lung cancer and to correlate those with histopathological findings. METHODS: This was a retrospective study involving 212 patients with a confirmed diagnosis of lung cancer by cytological evaluation of BAL specimens or by histopathological evaluation of endobronchial or transbronchial biopsy specimens. The data were collected at the Respiratory Endoscopy Sector of Hospital Sao Salvador, located in the city of Goiânia, Brazil, between 2005 and 2010. The endoscopic findings were classified as endoscopically visible tumor, endoscopically invisible tumor, mucosal injury, as well as being classified by the presence/type of secretion. The visible tumors were also classified according to their location in the tracheobronchial tree. RESULTS: Endobronchial mass (64%) and mucosal infiltration (35%) were the main endoscopic findings. The histological type was determined in 199 cases, the most prevalent types being squamous carcinoma, in 78 (39%), adenocarcinoma, in 42 (21%) small cell carcinoma, in 24 (12%), and large cell carcinoma, in 2 (1%). More than 45% of the visible tumors were at the upper bronchi. Squamous carcinoma (n = 78) was most commonly visualized as an endobronchial mass (in 74%), mucosal infiltration (in 36%), luminal narrowing (in 10%), or external compression (in 6%). CONCLUSIONS: Our results show that the endobronchial mass is the most common bronchoscopic finding that is suggestive of malignancy. Proportionally, mucosal infiltration is the most common finding in small cell carcinoma. In adenocarcinoma, luminal narrowing, external compression, mucosal injury, and endobronchial secretion prevail.

Efeito da sazonalidade climática na ocorrência de sintomas respiratórios em uma cidade de clima tropical

OBJECTIVE: To evaluate the effect that seasonality has on the occurrence of respiratory symptoms in a Brazilian city with a tropical climate. METHODS: This was a cross-sectional study, in which data related to subjects who sought outpatient treatment at a primary health care clinic in the city of Goiânia, Brazil, were correlated with daily meteorological data. Over a one-year period, all the patients who met the inclusion criteria were interviewed on 44 distinct, randomly selected days (11 days per season). We used ANOVA in order to compare the means of the dependent variables by season. Correlations were drawn between each dependent variable and each meteorological variable. The effects of the meteorological variables were analyzed with an AutoRegressive Moving Average with eXogenous input (ARMAX) model. RESULTS: Of the 3,354 participants, 494 (14.6%) had respiratory symptoms. Although temperature variation alone had no effect on the number of individuals with respiratory symptoms, the low levels of humidity during winter resulted in a statistically significant difference among the seasons (p < 0.01). The mean minimum relative humidity on the three days prior to the interviews correlated negatively with the number of subjects with respiratory symptoms (p = 0.04). An ARMAX model including the same variable showed a statistically significant coefficient (p < 0.0001). CONCLUSIONS: In this sample, the number of subjects with respiratory symptoms increased significantly when the relative humidity dropped, and this increase could be predicted using meteorological data.