Objective: To describe the profile of patients with cystic fibrosis (CF). Methods: A prospective, cross-sectional study involving CF patients ≤ 18 years of age, evaluated between March and July of 2006 at a referral center in northeastern Brazil. Nutritional assessment was performed using Z scores for height/age (H/A), weight/age (W/A) and weight/height (W/H), as well as %weight/height (%W/H) and body composition measurements. Socioeconomic and clinical data were obtained. Results: Twenty-one patients were evaluated, 12 (57.1%) of whom were female. Mean age at diagnosis was 3.8 ± 3.9 years. The principal features at diagnosis were respiratory infection (85.7%), steatorrhea (66.7%) and nutritional deficit (47.6%). The mean Z scores for W/A, H/A and W/H were 0.73 ± 0.28, 0.34 ± 0.21 and 0.73 ± 0.35, respectively. Mean %W/H was 94.52 ± 1.58. The percentage of malnourished children assessed by Z score differed from that assessed by %W/H (nutritional deficit in 66.7% and 33.3%, respectively; p > 0.05). Socioeconomic status, clinical status and Shwachman score were better among well-nourished patients than among those classified as malnourished (p < 0.05 for Shwachman score). Conclusions: Normal nutritional status was identified based on nutritional indicators (W/A, H/A and W/H), whereas nutritional deficit was identified by assessing body composition. Socioeconomic factors proved favorable, especially maternal education and per capita income. Age at diagnosis was higher than that reported in the literature, although the Shwachman score and the incidence of respiratory infections demonstrated that the patients presented good clinical status.

Keywords: Cystic fibrosis; Nutritional assessment; Symptoms, clinical; Socioeconomic factors.

Objective: To analyze the clinical characteristics and evolution of a group of patients with positive sputum cultures for multidrug-resistant (MDR) Mycobacterium tuberculosis and treated at a referral center in the city of Rio de Janeiro, Brazil. Methods: Based on the positive results in sputum cultures for MDR M. tuberculosis, 50 patients were selected, and their clinical data were obtained from the Brazilian Ministry of Health MDR-TB Database. The frequencies of noncompliance, relapses, failures and previous treatments for TB up to diagnosis of MDR-TB were compiled. The radiological patterns were classified as unilateral or bilateral, and with or without cavitation. Two years after the end of the standard treatment for MDR-TB, the outcome (cure, failure, noncompliance or death) for each patient was evaluated and reassessed every two years. The post-treatment follow-up period was eight years. Results: The mean number of previous treatments was 2.3 ± 0.9. The mean interval between the initial diagnosis and the development of MDR-TB was 2.0 ± 1.7 years. Two years after the initial treatment for MDR-TB, 2 patients had abandoned treatment, 8 had died, 18 had been cured, and 22 had presented treatment failure. The bivariate analysis showed that bilateral pulmonary involvement and cavitary pattern markedly reduced the chances for cure, with a relative risk of 1-0.6 (40%) and 1-0.7 (30%), respectively. At the end of the follow-up period, 2 patients had abandoned treatment, 9 had presented treatment failure, 17 had been cured, and 22 had died. Conclusions: Bilateral pulmonary involvement and cavity pattern greatly reduced the chances for cure of the patients with MDR-TB. Most patients who presented treatment failure died within the 8-year follow-up period.

Keywords: Tuberculosis, multidrug-resistant; Treatment outcome; Disease-free survival; Treatment refusal; Treatment failure.

Abstract Objective: To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma, to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response. Methods: Prospective cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia, Brazil. The study comprised 160 patients with severe asthma, monitored for 180 days in order to evaluate adherence (dependent variable) to the prescribed inhaled corticosteroid. Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a standardized questionnaire. Patients recorded the missed doses in a diary. Results: Of the 160 patients, 158 completed the study. Adherence rate was 83.8%. Of the 158 patients, 112 (70.9%) were considered adherent (cut-off point: 80% of prescribed doses administered). There was a significant association between asthma control and adherence to treatment. Predictors of poor adherence were adverse effects, living far from the referral center, limited resources to pay for transportation and dose schedule. Other factors, such as depressive symptoms, religion and economic status, were not associated with poor adherence. Conclusions: Adherence to asthma treatment was high and was associated with the clinical response to treatment, in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center.

Keywords: Asthma; Directly observed therapy; Treatment outcome; Patient compliance; Pharmacy.

Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

Keywords: Alpha-1 antitrypsin; Emphysema; Alleles.

Objective: Cystic fibrosis (CF) is a chronic multisystemic hereditary disease for which a multidisciplinary approach must be taken. The objective of this study was to show the evolution of a group of patients with CF after the implementation of multidisciplinary treatment. Methods: A retrospective study involving 19 patients (6-29 years of age) under clinical follow-up treatment at the University of São Paulo at Ribeirão Preto School of Medicine Hospital das Clínicas, located in the city of Ribeirão Preto, Brazil. The patients were divided into two groups: 6-12(6-12 years of age) and 13+ (> 12 years of age). We collected data regarding body mass index (BMI), Zscore, Shwachman score (SS), number of exacerbations/year, chronic colonization by Pseudomonas aeruginosa, and spirometric measurements (FVC, FEV1, FEV1%, and FEF25-75%). Data were collected at two different time points (before and after the implementation of the multidisciplinary treatment) and were analyzed with the Wilcoxon signed rank test. Results: The median age at the onset of symptoms was 10 months. In the 6-12 group, only BMI and FVC increased significantly. Although the other spirometric values increased, the differences were not significant. In the 13+ group, there were no significant differences between the two time points. There was a borderline significant decrease in SS and less than significant decreases in the spirometric measurements. However, the number of patients with alterations in volumes and flows decreased in both groups. Conclusions: Although our patient sample was small, the lack of changes in the spirometric parameters might reflect clinical and functional stability. In all of the patients evaluated, clinical, functional, and nutritional parameters remained stable throughout the study period. The implementation of a multidisciplinary approach might have contributed to this result.

Keywords: Cystic fibrosis; Spirometry; Body mass index; Physical therapy modalities.

Objective: To determine the relative frequency of hypomagnesemia among patients with chronic airflow limitation treated as outpatients at a referral center in the northern part of the state of Paraná between 2000 and 2001, as well as to determine whether hypomagnesemia correlates with hypoxia, with other electrolyte disturbances and with the severity of airflow limitation. Methods: This was a descriptive study of the relative frequency of hypomagnesemia in 72 patients with chronic airflow limitation. All of the patients were submitted to blood tests to determine serum levels of magnesium and other electrolytes, as well as to staging of the underlying disease. Results: The prevalence of hypomagnesemia was 27.8%. The mean age was 65 ± 9.9 years, and there was a predominance of males. The mean forced expiratory volume in one second was 1.31 ± 0.52 L. Most of the patients (68.1%) were found to be in the advanced stages of the disease. Hypomagnesemia was not found to correlate with other electrolyte disturbances, hypoxemia or disease stage. Conclusion: The high frequency of patients in the advanced stages is likely attributable to the fact that the outpatient facility is a referral center for the region. Further studies should be conducted in order to determine the probable causes of this high prevalence of hypomagnesemia.

Keywords: Magnesium/blood; Pulmonary ventilation; Pulmonary disease, chronic obstructive; Respiratory insufficiency

Objective: Massive hemoptysis is one of the most serious complications in patients with cystic fibrosis (CF). This study aimed to evaluate the hemoptysis-free period following bronchial and non-bronchial artery embolization (BAE/non-BAE) in CF patients and to investigate predictors of recurrent bleeding and mortality by any cause. Methods: This was a retrospective cohort study of CF patients = 16 years of age undergoing BAE/non-BAE for hemoptysis between 2000 and 2017. Results: We analyzed 39 hemoptysis episodes treated with BAE/non-BAE in 17 CF patients. Hemoptysis recurrence rate was 56.4%. Of the sample as a whole, 3 (17.6%) were hemoptysis-free during the study period, 2 (11.8%) underwent lung transplantation, and 3 (17.6%) died. The median hemoptysis-free period was 17 months. The median hemoptysis-free period was longer in patients with chronic infection with Pseudomonas aeruginosa (31 months; 95% CI: 0.00-68.5) than in those without that type of infection (4 months; 95% CI: 1.8-6.2; p = 0.017). However, this association was considered weak, and its clinical significance was uncertain due to the small number of patients without that infection. Conclusions: BAE appears to be effective in the treatment of hemoptysis in patients with CF.

Keywords: Cystic fibrosis; Hemoptysis; Bronchial arteries; Embolization, therapeutic.

Objective: To assess the determining factors for Mycobacterium tuberculosis multidrug resistance at a referral center for infectious diseases in the state of Minas Gerais, Brazil. Methods: A retrospective case-control study was conducted using data collected from September of 2000 to January of 2004. During this period, 473 cultures presenting growth of M. tuberculosis, corresponding to 313 patients, were submitted to susceptibility tests at the Central Laboratory of Minas Gerais. Cases presenting resistance to at least rifampin and isoniazid were classified as cases of multidrug resistance and were selected for study. These cases were paired to control group cases of drug-susceptible tuberculosis at a ratio of 1:3. Clinical and demographic data were analyzed using univariate and multivariate analyses. Results: During the study period, 12 (3.83%) cases of multidrug-resistant tuberculosis were identified. In the univariate analysis, multidrug-resistant tuberculosis was found to be more common among male patients, as well as among those testing positive in the sputum smear microscopy, those with cavitations larger than 4 cm in diameter and those having been previously treated for tuberculosis (p = 0.10 for all). After the multivariate analysis, only previous treatment for tuberculosis remained statistically significant (p = 0.0374), with an odds ratio of 14.36 (1.96-176.46). Conclusion: In the present study, previous treatment for tuberculosis was found to be an independent risk factor for multidrug-resistant tuberculosis.

Keywords: Mycobacterium tuberculosis; Tuberculosis, multidrug-resistant; Tuberculosis; Microbial sensitivity tests; Risk factors

Objective: To determine the relationship between nutritional status and dietary intake in patients with cystic fibrosis. Methods: Cross-sectional study involving 85 cystic fibrosis patients between 6 and 18 years of age. Dietary intake was evaluated by the 3-day diet record (weighing the food consumed). The outcome measures were the following nutritional status indicators: weight/height (W/H%) percentage, body mass index (BMI) percentiles, Z score for weight/age (W/A), Z score for height/age (H/A) and percentage of dietary intake compared with the Recommended Dietary Allowance (RDA). Results: The prevalence of well-nourished patients was 77.7%, using BMI above the 25th percentile as the cut-off value, and the W/H% was above 90% in 83.5%. The mean dietary intake, evaluated in 82 patients, was 124.5% of the RDA. In the univariate logistic regression analyses, we found a significant association between the independent variable calorie intake and the Z score for W/A. The multivariate analysis, based on the Z score for H/A and adjusted for FEV1, methicillin-resistant Staphylococcus aureus colonization and number of hospitalizations, demonstrated that a 1% increase in the calorie intake decreases the chance of having short stature by 2% (OR: 0.98; 95% CI: 0.96-1.00). Maternal level of education showed a borderline association (p = 0.054). Conclusions: The prevalence of malnutrition was low in this sample of patients. The study model demonstrated an association between dietary intake and nutritional status. Dietary intake was a predictive factor of statural growth in patients with cystic fibrosis.

Keywords: Cystic fibrosis; Nutritional status; Diet records; Child; Adolescent.

Objective: To determine primary and acquired resistance to pyrazinamide in Mycobacterium tuberculosis strains isolated in sputum samples from patients with pulmonary tuberculosis. Methods: This was a prospective, descriptive study conducted between April and November of 2011 at a referral hospital for tuberculosis in the city of Recife, Brazil. Cultures, drug sensitivity tests, and tests of pyrazinamidase activity were conducted in a private laboratory in Recife. Results: Of the 71 patients included in the study, 37 were treatment-naïve and 34 represented cases of retreatment. Pyrazinamide-resistant strains were isolated in 14 (41.2%) of the 34 patients who had previously been treated for tuberculosis and in none of the 37 treatment-naïve patients. Of the 14 isolates, 10 (90.9%) tested negative for pyrazinamidase activity. A total of 60 isolates tested positive for pyrazinamidase activity. Of those, 56 (93.3%) were found to be sensitive to pyrazinamide. Conclusions: The high frequency of pyrazinamide-resistant strains (41.2%) in patients previously treated for tuberculosis highlights the need for drug susceptibility testing prior to the adoption of a new treatment regimen.

Keywords: Mycobacterium tuberculosis; Pyrazinamide; Tuberculosis, multidrug-resistant

Objective: To evaluate the risk factors for the development of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) in patients treated at a tertiary referral hospital. Methods: This was a cross-sectional study based on data obtained from patients treated at the Júlia Kubitschek Hospital, located in the city of Belo Horizonte, Brazil, between October of 2012 and October of 2014. We evaluated sociodemographic, behavioral, clinical, and radiological variables. The outcome considered to identify associations between tuberculosis and the explanatory variables was the treatment prescribed. To evaluate the associations between MDR-TB and the same explanatory variables, the change in MDR-TB treatment was considered. Results: The factors associated with tuberculosis were alcoholism, comorbidities, pulmonary cavitations, and a radiological pattern suggestive of tuberculosis. Cavitation and previous treatment for tuberculosis were associated with MDR-TB. Conclusions: Despite the significant progress made in the fight against tuberculosis, there is a need for coordinated actions that include social protection measures and patient support.

Keywords: Tuberculosis; Risk factors; Tuberculosis, multidrug-resistant.

Objective: To determine the epidemiological profile of inpatients at a TB referral hospital. Methods: This was a descriptive, retrospective study of the medical charts of patients with TB hospitalized at the Hospital Estadual Santa Maria (HESM), in the city of Rio de Janeiro, Brazil, between January of 2002 and December of 2003. Data were collected using a standardized form. Results: Of the 451 patients included in the study, 313 (69.4%) had been referred to the HESM from health care clinics, and 302 (67.0%) were male. Most of the patients were in the 30-59  year age bracket, 443 (98.2%) lived in the greater metropolitan region of Rio de Janeiro, and 298 (66.1%) lived in the city of Rio de Janeiro itself. The most common reason for hospitalization was poor health status (in 237, 52.5%). The most common comorbidity was AIDS (in 137, 30.4%). The most common signs and symptoms at admission were weight loss, fever and productive cough. Sputum smear microscopy was positive in 122 (71.0%) of the patients presenting with productive cough at admission. Of the 212 patients being retreated, 156 (73.6%) reported noncompliance with previous treatment. Regarding the outcome, 273 (65.8%) of the patients were referred to municipal health care centers, 83 (18.4%) died, 44 (9.8%) were cured, and 27 (6%) were discharged against medical advice. Conclusions: Providing hospitals specializing in TB is relevant for TB control, especially in metropolitan regions. In addition to taking biosafety measures, these hospitals must be prepared to treat patients with TB-related comorbidities and social problems. This study has resulted in improvements at the HESM.

Keywords: Tuberculosis; Epidemiology; Hospitalization.

Objective: To analyze the clinical, etiological, and epidemiological aspects of community-acquired pneumonia (CAP) in hospitalized individuals. Methods: We prospectively studied 66 patients (> 14 years of age) with CAP admitted to the Hospital Estadual Sumaré, located in the Sumaré microregion of Brazil, between October of 2005 and September of 2007. We collected data related to clinical history, physical examination, pneumonia severity index (PSI) scores, and laboratory tests (blood culture; sputum smear microscopy and culture; serology for Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila; and detection of Legionella sp. and Streptococcus pneumoniae antigens in urine). Results: The mean age of patients was 53 years. Most had a low level of education, and 55.7% presented with at least one comorbidity at the time of hospitalization. The proportion of elderly people vaccinated against influenza was significantly lower among the inpatients than in the general population of the Sumaré microregion (52.6% vs. > 70%). Fever was less common among the elderly patients (p < 0.05). The clinical evolution was associated with the PSI scores but not with age. The etiology was confirmed in 31 cases (50.8%) and was attributed to S. pneumoniae, principally detected by the urinary antigen test, in 21 (34.4%), followed by C. pneumoniae, in 5 (8.2%). The mortality rate was 4.9%, and 80.3% of the patients were classified as cured at discharge. Conclusions: The knowledge of the etiologic profile of CAP at the regional level favors the appropriate choice of empirical treatment, which is particularly relevant in elderly patients and in those with comorbidities. The lack of influenza vaccination in elderly patients is a risk factor for hospitalization due to CAP.

Keywords: Chlamydophila pneumoniae; Community-acquired infections; Pneumonia; Streptococcus pneumoniae; Influenza vaccines.

Objective: To evaluate the use of inhaler devices by patients with severe asthma treated via the Programa para o Controle da Asma e Rinite Alérgica na Bahia (ProAR, Bahia State Asthma and Allergic Rhinitis Control Program), recording the frequency of their errors in performing key steps and the relationship between such errors and the lack of asthma control. Methods: A cross-sectional study involving 467 patients enrolled in the ProAR in the city of Salvador, Brazil. The devices evaluated were metered dose inhalers (MDIs), with or without a spacer, and dry powder inhalers (DPIs; Pulvinal® or Aerolizer®). For the assessment of the inhalation technique, a checklist was used; the patients were asked to demonstrate the technique so that an interviewer could observe all of the steps performed. For the assessment of asthma control, we used the 6-item asthma control questionnaire. Results: Most of the patients showed appropriate inhalation techniques when using the devices. When using an MDI, few patients made mistakes in the key step of "coordinating activation and inhalation" (5.2% and 9.1% with and without the use of a spacer, respectively). During Pulvinal® use, 39% of the patients did not inhale quickly and deeply, compared with only 5.8% during Aerolizer® use. Of the patients that made use of Aerolizer® alone, 71.3% appropriately performed all of the essential steps, and their asthma was controlled. Conclusions: Most of the patients in this sample, all of whom had been submitted to periodic checks of their inhalation technique (as part of the program), used the devices appropriately. Proper inhalation technique is associated with asthma symptom control.

Keywords: Asthma; Administration, inhalation; Metered dose inhalers; Dry powdered inhalers.

Objective: To evaluate the association between nutritional status measurements and pulmonary function in children and adolescents with cystic fibrosis. Methods: We evaluated the nutritional status of 48 children and adolescents (aged 6-18 years) with cystic fibrosis based on body mass index (BMI) and body composition measurements-mid-arm muscle circumference (MAMC) and triceps skinfold thickness (TST)-at a referral center in the city of Rio de Janeiro, Brazil. Pulmonary function was assessed by means of spirometry, using FEV1 to classify the severity of airway obstruction. We used Student's t-tests for comparisons between proportions and linear regression analysis for associations between continuous variables. The level of significance was set at p < 0.05. Results: The evaluation of nutritional status based on BMI identified a smaller number of malnourished patients than did that based on MAMC (14 vs. 25 patients, respectively). Most of the patients presented mild pulmonary disease. Mean FEV1 was 82.5% of predicted. Pulmonary function was found to correlate significantly with BMI, MAMC and TST (p = 0.001, p = 0.001 and p = 0.03, respectively). All subjects with moderate or severe pulmonary involvement were considered malnourished based on BMI and body composition parameters. Of the 25 patients considered malnourished based on body composition (MAMC), 19 were considered well-nourished based on their BMI. Conclusions: In the present study, all nutritional status measurements correlated directly with the pulmonary function of children and adolescents with cystic fibrosis. However, body composition measurements allowed earlier detection of nutritional deficiencies.

Keywords: Cystic fibrosis; Body composition; Spirometry; Nutrition assessment.

Objective: To determine the frequency of six mutations (F508del, G542X, G551D, R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a referral center, on the basis of abnormal results in two determinations of sweat sodium and chloride concentrations. Methods: This was a cross-sectional study involving 70 patients with CF. The mean age of the patients was 12.38 ± 9.00 years, 51.43% were female, and 94.29% were White. Mutation screening was performed with polymerase chain reaction (for F508del), followed by enzymatic digestion (for other mutations). Clinical analysis was performed on the basis of gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman-Kulczycki (SK) score. Results: All of the patients showed pulmonary symptoms, and 8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13 (25.0%) of the patients, respectively. There was no association between F508del mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X, R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005-0.826). Conclusions: In 50% of the alleles studied, the molecular diagnosis of CF was confirmed by identifying a single mutation (F508del). If we consider the analysis of the six most common mutations in the Brazilian population (including F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied.