Objective: Children are an important demographic group for understanding overall tuberculosis epidemiology, and monitoring of childhood tuberculosis is essential for appropriate prevention. The present study sought to characterize the spatial distribution of childhood tuberculosis notification rates in continental Portugal; identify high-risk areas; and evaluate the association between childhood tuberculosis notification rates and socioeconomic deprivation. Methods: Using hierarchical Bayesian spatial models, we analyzed the geographic distribution of pediatric tuberculosis notification rates across 278 municipalities between 2016 and 2020 and determined high-risk and low-risk areas. We used the Portuguese version of the European Deprivation Index to estimate the association between childhood tuberculosis and area-level socioeconomic deprivation. Results: Notification rates ranged from 1.8 to 13.15 per 100,000 children under 5 years of age. We identified seven high-risk areas, the relative risk of which was significantly above the study area average. All seven high-risk areas were located in the metropolitan area of Porto or Lisbon. There was a significant relationship between socioeconomic deprivation and pediatric tuberculosis notification rates (relative risk = 1.16; Bayesian credible interval, 1.05-1.29). Conclusions: Identified high-risk and socioeconomically deprived areas should constitute target areas for tuberculosis control, and these data should be integrated with other risk factors to define more precise criteria for BCG vaccination.

Keywords: Child; Poverty; Vaccination; Mycobacterium bovis.

The epidemiological relevance of tuberculosis is directly related to the socioeconomic profile of a given country. Vulnerability to tuberculosis is influenced by biological factors (e.g., malnutrition, HIV infection, and age) and social factors (e.g., unhealthy housing, high population density, inappropriate working conditions, and lack of access to health services). In many cases, multiple vulnerabilities occur in conjunction. We propose here a reflection on tuberculosis from the point of view of the social determinants of health, as well as the costs associated with its diagnosis and treatment in Brazil, based not only on data in the international literature but also on evidence related to the national context. Given the magnitude of tuberculosis as a socially mediated disease, there is an evident need for greater involvement of health professionals and of the scientific community to implement relevant operational and research measures to understand the social conditions influencing the health-illness continuum for tuberculosis patients. Although the recent economic crisis in Brazil has contributed to increased mortality from all causes, including tuberculosis, health and social protection expenditures have mitigated detrimental health effects. The evidence presented here underscores the importance of public social protection policies for minimizing the effects of tuberculosis indicators, with the aim of eliminating tuberculosis in Brazil.

Keywords: Tuberculosis; Social determinants of health; Cost of illness; Costs and cost 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 the factors associated with smoking experimentation and initiation among adolescent students (11-14 years of age). Methods: A cross-sectional, population-based study involving adolescent (middle and high school) students at public and private schools in the city of Salvador, Brazil. A multiple-stage sampling protocol was used. The participants completed an anonymous, voluntary, self-report questionnaire. The dependent variables were age at smoking experimentation and smoking initiation. Sociodemographic and educational variables, as well as those related to media influence and alcohol consumption, were considered independent variables. Multivariate logistic regression analysis was performed, followed by analysis of the fit of the final logistic regression model. Results: The prevalence of smoking experimentation was 16.1% (95% CI: 15.1-17.2). Of the 5,347 students evaluated, 757 had experimented with cigarettes, and 462 (61.2%) of those 757 had done so before the age of 15 (mean age at smoking experimentation, 13.9 ± 1.8 years). Smoking initiation was associated with paternal smoking (OR = 1.53; 83% CI = 1.07-2.19) and with media influence (OR = 2.43; 83% CI: 1.46‑4.04). Smoking experimentation was associated with alcohol consumption (OR = 6.04; 83% CI: 4.62-7.88), having friends who smoke (OR = 3.18; 83% CI: 2.54-3.99), having a boyfriend/girlfriend who smokes (OR = 3.42; 83% CI: 1.78-6.56), and coercive/aggressive educational interventions by the parents (OR = 1.60; 83% CI: 1.26‑2.04). Conclusions: Alcohol consumption and the influence of peers and relatives who smoke showed a strong association with smoking experimentation. Paternal smoking and media influence were found to increase the chances of adolescent smoking.

Keywords: Smoking; Adolescence; Health education; Cross-sectional studies; Epidemiologic factors; Brazil.

It has been well established that, in addition to the pulmonary involvement, COPD has systemic consequences that can lead to peripheral muscle dysfunction, with greater muscle fatigue, lower exercise tolerance and lower survival in these patients. In view of the negative repercussions of early muscle fatigue in COPD, the objective of this review was to discuss the principal findings in the literature on the metabolic and bioenergy determinants of muscle fatigue, its functional repercussions, as well as the methods for its identification and quantification. The anatomical and functional substrate of higher muscle fatigue in COPD appears to include lower levels of high-energy phosphates, lower mitochondrial density, early lactacidemia, higher serum ammonia and reduced muscle perfusion. These alterations can be revealed by contraction failure, decreased firing rates of motor units and increased recruitment of motor units in a given activity, which can be functionally detected by a reduction in muscle strength, power and endurance. This review article also shows that various types of muscle contraction regimens and protocols have been used in order to detect muscle fatigue in this population. With this understanding, rehabilitation strategies can be developed in order to improve the resistance to muscle fatigue in this population.

Keywords: Pulmonary disease, chronic obstructive; Neuromuscular manifestations; Muscle fatigue; Exercise tolerance; Energy metabolism; Evaluation.

Introduction: The diagnosis of diffuse lung disease is still a challenge for the pediatric intensive care physician. Routine clinical examinations and laboratory tests are frequently negative. The objective of this study was to evaluate the diagnostic potential, the impact on therapy and the rate of complications of open lung biopsy in children with undiagnosed diffuse lung disease, respiratory failure and inappropriate response to initial therapy. Methods: From January 1987 to January 1997, 29 children with diffuse pulmonary disease of unknown etiology, respiratory failure (PaO2 /FiO2 < 300) and no response to previous treatments were considered for open lung biopsy. Newborns, children with known chronic pulmonary disease and children with untreatable shock or coagulopathy were excluded. All biopsies were performed by a thoracic surgeon by a microthoracotomy in the lung shown to be the most affected by X-ray examination. Tissue samples were analyzed in terms of cultures, light microscopy, electron microscopy and immunofluorescence microscopy, according to the pathologist's decision. Results: All biopsies (100%) resulted in at least one histological diagnosis and in 20 patients (68.9%) it was obtained a specific diagnosis. The most frequent histological patterns found were: non-specific interstitial pneumonitis with variable degrees of fibrosis in 18 cases; bronchiolitis in eight cases and pulmonary hypertension in three cases. Regarding the most frequent specific diagnosis, six children were found with cytomegalovirus infection, three with Pneumocystis carinii, three with adenovirus and three with respiratory syncytial virus infection. These data induced a change in therapy in 20 children (68.9%). The most frequent changes in therapy were the use of corticosteroids in 14 children and a review of the antibiotic regimen in six patients. Seven patients (24.1%) presented with complications that were easily resolved. There were 13 deaths, probably due to the critical conditions of these patients, all unrelated to the procedure. Conclusions: Open lung biopsy, though an invasive procedure, should be considered in the evaluation of selected children with undiagnosed diffuse lung disease, respiratory failure and with no satisfactory response to previous therapies.

Objective: To evaluate the asthma prevalence in the Federal District of Brazil, using the questionnaire developed for the International Study of Asthma and Allergies in Childhood to look for correlations with socioeconomic levels. Methods: A total of 6437 children (3183 from six to seven years old and 3254 from thirteen to fourteen years old), attending public or private schools, were evaluated. The data were analyzed by gender and socioeconomic status (chi-square test). Results: The prevalence of asthma in the Federal District was 12.1% among the six- and seven-year-olds and 13.8% among the thirteen- and fourteen-year-olds (p < 0.04). In the six-to-seven age bracket, asthma prevalence was significantly greater, and asthma-related symptoms were more frequent, among males (p < 0.001). In contrast, asthma-related symptoms were more frequent among females in the thirteen-to-fourteen age bracket (p < 0.05). Children belonging to the lowest socioeconomic class, as determined by the responses given on the questionnaire completed by the parents, presented the highest prevalence of asthma, regardless of age bracket (p < 0.001). Among such children, asthma-related symptoms were also more frequent (p < 0.05). In the thirteen-to-fourteen age bracket, the prevalence of asthma was greater among those belonging to the highest socioeconomic class (p = 0.001). Conclusions: Overall, economically disadvantaged children more frequently presented asthma-related symptoms and experienced asthma attacks that were of greater severity. In addition, the prevalence of suspected asthma was higher than that of diagnosed asthma in this group, suggesting that asthma is underdiagnosed in children belonging to the lowest socioeconomic class.

Keywords: Asthma/epidemiology; Asthma/diagnosis; Socioeconomic factors; School health; Questionnaires

Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

Keywords: Tuberculosis, pulmonary/prevention & control; Mycobacterium tuberculosis; Lung diseases/etiology; Child; Adolescent.

Introduction: Bronchoscopy is useful in the diagnosis of tuberculosis suspects with a "negative" sputum smear. The objectives of this study were: to assess yield of bronchoalveolar lavage (BAL) and of transbronchial biopsy (TBB) both in HIV-positive patients (group 1) and immunocompetent individuals (group 2), based on simple and most available laboratory techniques in clinical practice. Patients and methods: The authors performed 319 bronchoscopies in 302 patients. BAL and TBB were sequentially performed in the same lung in all cases. Tuberculosis was diagnosed based on the results of acid-fast stains (AFS) from the lavage (ZN), culture for mycobacteria (LJ), and histological examination of biopsies (HE and ZN). Results: Tuberculosis was the final diagnosis in 28 exams of group 1 (n = 214) and in 35 of group 2 (n = 105). There were abnormal endoscopic findings respectively in 3 and 10 patients. In group 1, AFS were positive in 7 cases, culture of BAL in 14, and TBB in 19. In group 2, AFS were positive in 13 cases, culture in 17, and biopsies in 31. TBB results compared to BAL were in concordance for group 1 (p = 0.823) and different for group 2 (p = 0.022). Immediate results (AFS and TBB) compared to later positive results of culture were similar for group 1 (p = 0.066) but not for group 2 (p = 0.001). There were eight episodes of pneumothorax (2.5%) and one death (0.36%). Conclusions: Both BAL and TBB should be performed whenever possible, aiming towards a higher yield of bronchoscopy in the diagnosis of tuberculosis. Both methods complement each other in immunocompetent patients, whereas TBB establishes a faster diagnosis for HIV-infected patients if associated to AFS.

Keywords: Bronchoscopy/methods. Smear-negative tuberculosis/diagnosis. Opportunistic infections related to AIDS/diagnosis.

Objective: To evaluate the performance of nested PCR (nPCR) in detecting the Mycobacterium tuberculosis complex in blood samples of patients suspected of having TB, in order to determine its potential for use as an auxiliary tool in the laboratory diagnosis of TB in children. Methods: Detection of the M. tuberculosis complex in blood samples using as a target the insertion sequence IS6110 of the genomic DNA of the bacillus. Blood samples of 120 patients were evaluated. All of the patients were under 15 years of age at the time of their treatment at public hospitals in the city of Recife, Brazil (between January of 2003 and August of 2005). Attending physicians at the hospitals diagnosed TB based on the criteria recommended by the American Thoracic Society. The nPCR amplified a 123-bp fragment with outer oligonucleotides (IS1/IS2) and, in the subsequent reaction, using inner oligonucleotides (IS3/IS4), generating an 81-bp amplicon. Results: Active or latent TB was found in 65 patients, TB was ruled out in 28 suspected cases, and 27 patients were TB-free (controls). The sensitivity of nPCR was 26.15% and was significantly higher for the extrapulmonary form of the disease (55.56%) than for the pulmonary form (18.18%). The specificity was 92.73%. Conclusions: Despite the difficulties in diagnosing TB in children and the low number of cases evaluated in the present study, nPCR in blood samples proved to be a rapid and specific technique, albeit one with low sensitivity. In order to establish its true usefulness in the diagnosis of paucibacillary forms, especially extrapulmonary TB, further studies need to be carried out with a larger sample of children and analyzing biological specimens other than blood.

Keywords: Tuberculosis; Diagnosis; Blood; Polymerase chain reaction.

Objectives: To evaluate the contribution of Ultra to the diagnosis of pediatric pulmonary tuberculosis (PTB). Methods: We analyzed prospective data from children and adolescents with presumed PTB whose specimens were tested with Ultra between January 2020 and December 2022. Diagnosis was based on clinical-radiological criteria, clinical response after a two-month treatment period, and microbiological analysis. Ultra was considered positive with a result of 'Detected' and 'Traces' in children under 10 years and in HIV-infected individuals. Fisher's exact test was used for group comparisons, and McNemar's test was used to compare Ultra results with the diagnostic presumption. The study was approved by the Ethics Committee (CAAE No. 02173518.2.0000.5264). Results: A total of 41 patients were included, of whom 63% (26/41) were diagnosed with PTB. Among these, 9/26 (34%) had positive results only through Ultra, with negative AFB and culture. The sensitivity and specificity of Ultra were 50% (13/26) and 100% (15/15), respectively. The PPV was 100% (13/13), and the NPV was 54% (15/28). Of these 28 (68%) patients with negative Ultra results, 13 (46%) were diagnosed with PTB, mostly by MoH-SS. Considering culture as the reference, the PPV and NPV were 67% and 100%, respectively. Conclusions: Ultra significantly contributed to the diagnosis of pediatric PTB, proving to be a promising tool for paucibacillary forms of the disease. However, it should not be used alone. Integrating laboratory tests with clinical evaluation is essential to improving diagnostic accuracy and the management of pediatric TB.

Keywords: Pulmonary tuberculosis; children; adolescents; GeneXpert Ultra.

In many populations, the prevalence of asthma and atopy has increased in recent years. As a result, both conditions have become major public health problems. The possible influence of nutrition-related factors has been demonstrated in an increasing number of studies. Information regarding the role of breastfeeding, diet, nutritional status (obesity in particular), as well as regarding the immunologic responses triggered, helps to improve our understanding of the correlation between oxidative stress, bronchial inflammation, and the development of atopic and asthma symptoms. The article presents a review of the published literature on the relationships established between and among nutrition, asthma, and atopy over the last two decades.

Keywords: Asthma; Nutritional status; Breast feeding; Diet.

Tuberculosis is one of the major infectious diseases in developing countries, and the length of time for which the chain of transmission is maintained has been implicated as a major factor in the perpetuation of the disease. In this context, regulatory agencies in such countries have approved new diagnostic tools, which have been almost immediately incorporated into the national tuberculosis control programs. Health interventions have been increasingly investigated in clinical trials, including explanatory trials (in order to evaluate the beneficial effects of such interventions) and pragmatic trials (in order to aid in the decision-making process). We argue that the evaluation of new diagnostic techniques for the detection of tuberculosis should not escape this same logic of evaluation.

Keywords: Tuberculosis/diagnosis; Tuberculosis/prevention & control; Controlled clinical trial as topic.

Objectives: This study primarily aimed to investigate the clinical determinants of the Modified Incremental Step Test (MIST) in adults with non-cystic fibrosis bronchiectasis (NCFB). A secondary objective was to compare the cardiopulmonary responses after the MIST and Incremental Shuttle Walk Test (ISWT), two commonly adopted symptom-limited maximum field tests in chronic respiratory diseases. Methods: Forty-six patients with clinically stable bronchiectasis participated in this cross-sectional study. MIST and ISWT were performed to determine exercise capacity, while disease severity, fatigue, and quality of life were assessed using the Bronchiectasis Severity Index (BSI), the Fatigue Severity Scale (FSS), and St. George's Respiratory Questionnaire (SGRQ), respectively. Quadriceps muscle strength was evaluated using a hand-held dynamometer, walking speed with a wireless inertial sensing device, and the level of physical activity (steps/day) with a pedometer. Results: The BSI score, quadriceps muscle strength, daily step count, and the SGRQ total score explained 61.9% of the variance in the MIST (p < 0.001, R2 = 0.67, AR2 = 0.619). The BSI score (r = -0.412, p = 0.004), quadriceps muscle strength (r = 0.574, p = 0.001), daily step count (r = 0.523, p < 0.001), walking speed (r = 0.402, p = 0.006), FSS score (r = -0.551, p < 0.001), and SGRQ total score (r = -0.570, p < 0.001) correlated with the MIST. The patients achieved higher heart rates (HR), HR%, desaturation, dyspnea, and leg fatigue in the MIST compared to the ISWT (p < 0.05). Conclusions: Disease severity, quadriceps muscle strength, physical activity level, and quality of life were determinants of MIST. The advantages of the MIST, including higher cardiopulmonary response than ISWT and greater portability, which facilitates its use in various settings, make MIST the preferred choice for investigating symptom-limited exercise capacity in patients with NCFB.

Keywords: bronchiectasis, exercise capacity, step test, physical activity, walking speed, quality of life.

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.

Background: Knowledge of the rates of drug resistance is one of the pillars of tuberculosis control program evaluation. Data from low-resource countries are scarce and results are delayed due to the techniques employed. There is therefore an urgent need for evaluation of faster and less onerous testing methods. Objective: To compare the performance of rapid colorimetric assays for phenotyping that employ oxidationreduction indicators to determine the susceptibility profile of Mycobacterium tuberculosis with the gold-standard proportion method on Lowenstein-Jensen Medium. Method: We analyzed 166 M. tuberculosis strains of known susceptibility. Minimal inhibition concentrations for isoniazid and rifampicin were determined in microplates, using a liquid medium and Alamar Blue and tetrazolium bromide indicators. To measure agreement the Kappa value was used. Cutoff values between sensitive and resistant strains were defined as 0.2µg/mL and 1.0µg/mL for isoniazid and rifampicin, respectively. Results: There was 100% concordance between Alamar Blue and tetrazolium bromide methods in the determination of minimal inhibition concentrations. Agreement between the colorimetric method and the Lowenstein-Jensen was 95% for isoniazid and rifampicin. Using the colorimetric method, results were obtained within 7 days, in contrast to the 28 days required for the conventional method. Conclusions: Assays to determine minimal inhibition concentrations in liquid medium and employing oxidationreduction indicators proved to be rapid and inexpensive. This method has the potential to become a faster, alternative method for determining susceptibility of M. tuberculosis strains in developing countries.

Keywords: Mycobacterium tubercolis. Disease susceptibility. Isoniazid/therapeutic use. Rifampin/therapeutic use.