Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

Keywords: Cystic fibrosis; GRADE approach; Cystic fibrosis/drug treatment; Clinical practice guide.

Background: Host genetic factors may play a role in the susceptibility to active tuberculosis (TB), and several polymorphisms in different cytokine coding genes have been described and associated with diseases to date. Objectives: To investigate whether polymorphisms within the promoter region of the TNF-á (-238/-308) coding genes are associated to the occurrence of active TB. Methods: SNPs within the TNF-á gene were analyzed by PCR-RFLP among two groups of individuals: patients with TB (n = 234, and patients non TB (n = 113). Results: In this study, the presence of the -238A allele was associated with susceptibility to TB disease occurrence and severity (p = 0,00002; OR = 0,15; IC = 0,06-0,36. On the contrary, the -308A allele was associated with protection to the occurrence of another pulmonary diseases. Conclusions: These results suggest the importance of genetics studies on TB occurrence. Further studies are needed pursuing a better understanding of the human pathogenesis of M. tb.

Keywords: Tuberculosis/genetics. Polymorphism, single nucleotide/genetics. Tumor necrosis factor/genetics. Alleles. Genotype. Lung diseases.

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.

Keywords: Tuberculosis; Mycobacterium infections; Diagnosis; Tuberculosis, multidrug-resistant.

Purpose: To determine the effectiveness of alternative regimens for treating confirmed MDR TB cases in outpatient units: Methods: MDR TB cases were defined as culture isolation of M. tuberculosis resistant in vitro to at least rifampin/isoniazide and a third drug of standard regimens in Brazil, according to both the conventional method and the BACTEC system. Design: Multicentric non-randomized controlled clinical trial. From April 95 to December 97 187 patients were enrolled. As of April 98, there were 36 patients under treatment. The authors analyzed 149 patients that had an average 14 months of treatment duration. The regimens used were chosen according to sensitivity tests: 1) streptomycin (S)/ofloxacin (OFX)/terizidon (TZ)/ethambutol (E)/clofazimine (CZ) or capreomycin (CM)/OFX/TZ/CZ/E or amicacyn/OFX/TZ/E/CZ. Demography: Male, 68.4%; female, 31.5%; mean age-36.9 years; HIV prevalence 1.9%; primary resistance rate - 8%. Outcomes: cured-treated for 12 months with six months after two consecutive negative culture; abandoned-discontinued treatment and consultations; died - deaths due to TB after two months of treatment; failed - remained positive in culture throughout the 12 months. Results: 120 (79.5%) patients converted to negative culture within 3 months. Cured: 53%, failed 31%, died 6%, abandoned 10%. Conclusions: The major predictor to MDR TB in Brazil is previous irregular and/or incomplete treatment. Sputum conversion rate was high and favorable overall response was 53%. Clinical implications: Because TB is endemic in Brazil and the number of MDR cases due to acquired resistance is increasing, greater efforts are needed to implement supervised treatment in tuberculosis particularly for non compliant patients.

Keywords: Tuberculosis, treatment. Multidrug resistant tuberculosis.

Objective: To describe the factors associated with nonadherence to TB chemoprophylaxis in patients older than 15 years of age treated via referral TB control programs. Methods: A historical cohort study was carried out based on medical charts related to cases treated via referral TB control programs in the city of Vitória, Brazil, between 2002 and 2007. Cases of infection with Mycobacterium tuberculosis were stratified into two groups: health care workers (HCW group); and individuals who were not health care workers (NHCW group). Results: A total of 395 patients were included in the study: 35 in the HCW group and 360 in the NHCW group. The mean age in the HCW and NHCW groups was 34.8 and 32.4 years, respectively (p = 0.36). Of the 35 patients in the HCW group, 29 (82.9%) were female, compared with 180 (50.0%) of the 360 patients in the NHCW group. In the HCW and NHCW groups, respectively, 15 (42.9%) and 169 (46.9%) of the patients were contacts of TB cases. In addition, 9 (25.7%) and 157 (78.5%) the HCW and NHCW group patients, respectively, were HIV-infected. Nonadherence to chemoprophylaxis was 37.1% and 21.9% in the HCW and NHCW groups, respectively (p = 0.045). In the multivariate analysis, the factors associated with nonadherence were being a health care worker (OR = 8.60; 95% CI: 2.09-35.41), being HIV-infected (OR = 4.57; 95% CI: 1.2-17.5) and having had contact with a TB patient (OR = 2.65; 95% CI: 1.15-6.12). Conclusions: In order to improve adherence to TB chemoprophylaxis, new TB control program strategies are needed, especially for health care workers and HIV-infected patients.

Keywords: Tuberculosis; Chemoprevention; Isoniazid.

A comparative study to evaluate contamination in cultures of morning sputum samples, comparing those collected at home under currently recommended conditions and those collected under supervision after patient orientation and education. The home and supervised collection groups produced 43 and 76 sputum samples, respectively. The contamination rate was nearly 3-times higher among samples collected at home than among those collected under supervision (37% vs. 13%, p < 0.05; OR = 0.25). The simple educational and hygiene measures described can decrease the contamination rate among sputum samples collected for diagnostic culture.

Keywords: Tuberculosis/diagnosis; Sputum/microbiology; Culture techniques.

Objective: To evaluate the impact that Family Health Program (FHP) team training and active surveillance have on the detection of TB cases in a low-income community in the city of Fortaleza, Brazil. Methods: The study was performed in an area with approximately 25,000 inhabitants, served by a health care center with five FHP teams, in the city of Fortaleza, Brazil. Although all of the teams were trained, active surveillance was carried out only in one of the areas (area 5). We compared the number of TB cases detected in each of the five areas prior to and after the intervention. We also compared the number of TB cases detected in area 5 to the number of those detected in the other areas, as well as to the citywide number of reported TB cases in Fortaleza, within the same period. Results: The number of TB cases detected in the area studied increased from 1 in 2002 to 22 in 2004 (p < 0.05). There was no significant difference between the number of TB cases in area 5 and that observed for each of the other four areas (p > 0.05). There was a significant increase in the number of TB cases detected in the area studied when compared to the city as a whole (p < 0.05). Conclusions: Training and sensitization of FHP professionals were effective in promoting an increase in the number of TB cases detected in a low-income community.

Keywords: Tuberculosis; Communicable disease control; Family health program; Epidemiologic surveillance.