Objective: To determine the clinical and epidemiological profile of patients who are candidates for TNF-α inhibitor use and are classified as having latent tuberculosis (LTB), as well as to evaluate the outcomes of prophylactic treatment with isoniazid. Methods: A prospective descriptive analysis followed by an analytical, observational, cross-sectional study of the outcomes of prophylactic treatment in a group of 45 candidates for TNF-α inhibitor use. We evaluated the patients through anamnesis, clinical examination, chest X-ray, and tuberculin skin test (TST) using the Mantoux method. Results: The mean age was 45 years, and 56.0% of the patients were female. Chronic rheumatic diseases, chronic dermatological diseases, and Crohn's disease were present in 46.7%, 40.0%, and 13.3% of the patients, respectively. The mean TST induration was 14.6 mm (range: 5-30 mm). The majority (n = 30) of the 45 patients (66.7%) had an induration > 10 mm. In the 16 patients with BCG vaccination scars, the mean induration was 15.7 mm, and 14 of those patients had an induration > 10 mm. Chest X-ray results were considered normal, with minimal alterations, in 64.4% and 35.6% of the patients, respectively. The treatment with isoniazid was abandoned by 1 patient (2.2%) and completed by 41 (91.2%), whereas it was interrupted because of drug-induced hepatitis in 2 (4.4%), and 1 patient (2.2%) was transferred to another hospital. Of those who completed the treatment, 5 experienced mild side effects. Conclusions: Determining the profile of candidates for TNF-α inhibitor use is important for the management of LTB treatment and for the establishment of clinical protocols for the use and monitoring of the use of these medications.

Keywords: Tuberculosis; Latent tuberculosis; Tuberculin test; Isoniazid; Tumor necrosis factor-alpha.

Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

Keywords: Latent tuberculosis; Tuberculin test; Tumor necrosis factors/antagonists & inhibitors; Isoniazid.

Neuromuscular diseases affect alveolar air exchange and therefore cause chronic respiratory failure. The onset of respiratory failure can be acute, as in traumas, or progressive (slow or rapid), as in amyotrophic lateral sclerosis, muscular dystrophies, diseases of the myoneural junction, etc. Respiratory muscle impairment also affects cough efficiency and, according to the current knowledge regarding the type of treatment available in Brazil to these patients, it can be said that the high rates of morbidity and mortality in these individuals are more often related to the fact that they cough inefficiently rather than to the fact that they ventilate poorly. In this review, with the objective of presenting the options of devices available to support and substitute for natural ventilation in patients with neuromuscular diseases, we have compiled a brief history of the evolution of orthopedic braces and prostheses used to aid respiration since the end of the 19th century. In addition, we highlight the elements that are fundamental to the diagnosis of alveolar hypoventilation and of failure of the protective cough mechanism: taking of a clinical history; determination of peak cough flow; measurement of maximal inspiratory and expiratory pressures; spirometry in two positions (sitting and supine); pulse oximetry; capnography; and polysomnography. Furthermore, the threshold values available in the literature for the use of nocturnal ventilatory support and for the extension of this support through the daytime period are presented. Moreover, the maneuvers used to increase cough efficiency, as well as the proper timing of their introduction, are discussed.

Keywords: Respiratory insufficiency/diagnosis; Chronic disease; Respiratory insufficiency/therapy;

Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.

Keywords: Tuberculosis; Latent tuberculosis; Tuberculin skin test; Anti-TNF therapy; Tumor necrosis factor-alpha; Rheumatoid arthritis.

Objective: To determine the prevalence of latent tuberculosis infection (LTBI) and the risk of infection in patients with chronic kidney disease treated at a hemodialysis center. Methods: We included 307 patients with chronic kidney disease undergoing hemodialysis at the Mineiro Institute of Nephrology, located in the city of Belo Horizonte, Brazil. All of the patients were submitted to tuberculin skin tests (TSTs). We investigated the booster effect and TST conversion. If the initial TST (TST1) was negative, a second TST (TST2) was performed 1-3 weeks later in order to investigate the booster effect. If TST2 was also negative, a third TST (TST3) was performed one year after TST2 in order to determine whether there was TST conversion. Results: When we adopted a cut-off induration of 5 mm, the prevalence of LTBI was 22.2% on TST1, increasing by 11.2% on TST2. When we adopted a cut-off induration of 10 mm, the prevalence of LTBI was 28.5% on TST1, increasing by 9.4% on TST2. The prevalence of LTBI increased significantly from TST1 to TST2 (booster effect), as well as from TST2 to TST3 (p < 0.01 for both). In our sample, the mean annual risk of infection was 1.19%. Conclusions: In the population studied, the prevalence of LTBI was high, and the mean annual risk of infection was similar to that reported for the general population of Brazil, which suggests recent infection.

Keywords: Tuberculosis; Renal insufficiency, chronic; Tuberculin test.

Objective: To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. Methods: A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). Results: A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm3; viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. Conclusions: Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Keywords: Tuberculosis; Diagnosis; Therapeutics; Treatment outcome; HIV infections.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

Keywords: Tuberculosis, pulmonary; Arthritis, rheumatoid; Tumor necrosis factor-alpha; Infection.

Objective: To evaluate the usefulness of determining the inflammatory component of airway diseases (inflammometry) by induced sputum cell counts, as well as its influence on treatment decisions in a tertiary facility for the treatment of respiratory diseases. Methods: We analyzed 151 sputum samples from 132 consecutive patients referred for clinical sputum induction by five pulmonologists between July of 2006 and February of 2007. A structured questionnaire related to the reasons for requesting the test and to the therapeutic decision making based on test results was completed by each attending physician upon receiving the test results. Induced sputum was obtained and processed according to a technique previously described. Results: The principal motives for ordering the test were inhaled corticosteroid dose titration in patients with moderate-to-severe asthma (in 54.3%), investigation of chronic cough (in 30.5%), and monitoring airway inflammation in patients with bronchiectasis (in 7.3%) or chronic obstructive pulmonary disease (in 6%). Of the 82 patients with asthma, 47 (57%) presented eosinophilic bronchitis (>3% eosinophils). Nonasthmatic eosinophilic bronchitis was diagnosed in 9 (19%) of the 46 patients with chronic cough. Neutrophilic bronchitis (>65% neutrophils) was found in 13 patients, of which 5 had asthma, 2 had chronic cough, and 6 had chronic obstructive pulmonary disease/bronchiectasis. Based on the induced sputum results, the corticosteroid dose was modified in 48 asthma patients (64.7%). Conclusions: The systematic application of inflammometry using induced sputum cell counts can be beneficial for patients with airway diseases, particularly those with asthma or chronic cough.

Keywords: Sputum; Asthma; Bronchitis.

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 characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods: Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results: The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion: Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

Keywords: Latent tuberculosis infection; Interstitial lung diseases; Immunosuppression; Tuberculin test.

Objective: To analyze the association between clinical/epidemiological characteristics and outcomes of tuberculosis treatment in patients with concomitant tuberculosis and chronic kidney disease (CKD) in Brazil. Methods: We used the Brazilian Ministry of Health National Case Registry Database to identify patients with tuberculosis and CKD, treated between 2007 and 2011. The tuberculosis treatment outcomes were compared with epidemiological and clinical characteristics of the subjects using a hierarchical multinomial logistic regression model, in which cure was the reference outcome. Results: The prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%). The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes, in 22%. The characteristics that differentiated the ORs for treatment abandonment or death were age; alcoholism; AIDS; previous noncompliance with treatment; transfer to another facility; suspected tuberculosis on chest X-ray; positive results in the first smear microscopy; and indications for/use of directly observed treatment, short-course strategy. Conclusions: Our data indicate the importance of sociodemographic characteristics for the diagnosis of tuberculosis in patients with CKD and underscore the need for tuberculosis control strategies targeting patients with chronic noncommunicable diseases, such as CKD.

Keywords: Tuberculosis/epidemiology; Renal insufficiency, chronic/epidemiology; Risk factors; Logistic models.

Step tests are typically used to assess exercise capacity. Given the diversity of step tests, the aim of this review was to describe the protocols that have been used in healthy subjects and in patients with chronic lung disease. Step tests for use in healthy subjects have undergone a number of modifications over the years. In most step tests, the duration is variable (90 s-10 min), but the step height (23.0-50.8 cm) and stepping rate (22.5-35.0 steps/min) remain constant throughout the test. However, the use of a fixed step height and constant stepping rate might not provide adequate work intensity for subjects with different levels of fitness, the workload therefore being above or below individual capacity. Consequently, step test protocols have been modified by introducing changes in step heights and stepping rates during the test. Step tests have been used in patients with chronic lung diseases since the late 1970s. The protocols are quite varied, with adjustments in step height (15-30 cm), pacing (self-paced or externally paced), and test duration (90 s-10 min). However, the diversity of step test protocols and the variety of outcomes studied preclude the determination of the best protocol for use in individuals with chronic lung disease. Shorter protocols with a high stepping rate would seem to be more appropriate for assessing exercise-related oxygen desaturation in chronic lung disease. Symptom-limited testing would be more appropriate for evaluating exercise tolerance. There is a need for studies comparing different step test protocols, in terms of their reliability, validity, and ability to quantify responses to interventions, especially in individuals with lung disease.

Keywords: Pulmonary disease, chronic obstructive; Asthma; Cystic fibrosis; Idiopathic pulmonary fibrosis; Exercise tolerance; Exercise test.

Objective: To evaluate treatment compliance and use of inhaled medications of patients with asthma receiving complementary pharmaceutical care. Methods: A controlled prospective parallel study involving a study group and a control group. We selected 60 patients with persistent asthma and using metered-dose inhalers (MDIs), dry powder inhalers (DPIs) or both. The patients were evaluated three times over 60 days. Instructions were provided to the patients in the study group at all visits but only at the first visit to those in the control group. The patients using < 80% or > 120% of the total number of prescribed doses were classified as noncompliant. The inhalation technique was quantified by a scoring system. A satisfactory technique was defined as a score higher than 7 (maximum, 9) for MDIs and higher than 4 (maximum, 5) for DPIs. Results: The final study sample comprised 28 study group patients and 27 control group patients, of whom 18 (64.3%) and 20 (74.7%), respectively, were considered treatment compliant. From the first to the third visits, there were increases, in the study and control groups, in the median MDI-use score (from 3 [range, 0-5] to 8 [range, 8-9]; p < 0.001; and from 5 [range, 2-6] to 7 [range, 6-8]), as well as in the median DPI-use score (from 3 [range, 2-4] to 5 [range, 4-5] and from 3 [range, 2-4] to 4 [range, 3-5]). Conclusions: The counseling provided by the pharmacist to the patient was important to assist in the implementation of the appropriate inhalation technique, especially for MDI use.

Keywords: Asthma; Pharmaceutical services; Administration, inhalation;Metered dose inhalers; Medication adherence.

Objective: Lymphangioleiomyomatosis (LAM) is a rare disease that is currently considered a low-grade neoplasm with metastatic potential and variable progression. Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. The objective of the present study was to describe a case series of four patients with LAM in Brazil who showed significant improvement, particularly in their extrapulmonary manifestations, after treatment with sirolimus (at 1-4 mg/day). Methods: We describe four cases of LAM patients with different extrapulmonary manifestations who were treated with sirolimus. Results: After treatment with sirolimus for 12 months, one patient presented resolution of severe chylothorax; one had a significant reduction in renal angiomyolipoma volume; and one showed significant regression of retroperitoneal lymphangioleiomyomas and abdominal lymph node enlargement. After treatment with sirolimus for 6 months, the remaining patient had a significant reduction in the volume of a massive retroperitoneal lymphangioleiomyoma. Conclusions: Our findings confirm that mTOR inhibitors are beneficial for patients with LAM, especially those with extrapulmonary manifestations, such as renal angiomyolipoma, lymphangioleiomyomas, and chylous effusions. However, certain aspects, such as the optimal dose, duration of treatment, and long-term adverse effects, have yet to be sufficiently clarified for mTOR inhibitors to be incorporated into LAM management protocols.

Keywords: Neoplasms; Lymphangioleiomyomatosis/therapy; TOR serine-threonine kinases; Sirolimus.

Objective: Preventive treatment of active tuberculosis is one of the main strategies for reducing the incidence of tuberculosis. We sought to evaluate the rates of latent tuberculosis infection (LTBI) treatment completion with three months of once-weekly isoniazid plus rifapentine (3HP) and compare them with those for six to nine months of daily isoniazid (6H/9H). Methods: This was a retrospective cross-sectional study. Consecutive patients undergoing LTBI treatment with 3HP or 6H/9H were included in the study. Treatment completion rates and adverse effects were analyzed. Results: A total of 226 patients were included in the study: 113 in the 3HP group and 113 in the 6H/9H group. The frequency of adverse effects was not significantly different between the 3HP and 6H/9H groups. The 3HP group had a higher treatment completion rate (93.8%) than did the 6H/9H group (84.1%), the difference being significant. Conclusions: The rates of LTBI treatment completion appear to be higher with 3HP than with 6H/9H. Health care professionals should be vigilant in managing adverse effects to further maximize LTBI treatment completion.

Keywords: Tuberculosis, pulmonary; Latent tuberculosis/prevention & control; Mycobacterium tuberculosis.

Abstract Objective: To determine the validity and reproducibility of two subjective instruments to assess limitations in activities of daily living (ADLs) in patients with chronic obstructive pulmonary disease (COPD) in Brazil: the Pulmonary Functional Status and Dyspnea ­Questionnaire ‑ ­Modified version (PFSDQ-M) and the Medical Research Council (MRC) scale. Methods: Thirty patients with COPD (age, 67 ± 10 years; males, 17; forced expiratory volume in one second, 42% ± 13% of predicted) completed the Portuguese-language versions of the two instruments on two occasions, one week apart. The PFSDQ-M has three components: influence of dyspnea on ADLs, influence of fatigue on ADLs and change experienced by the patient with ADLs. The MRC scale is simple, with only five items, in which patients report the degree to which dyspnea limits their performance of ADLs. The traditional Saint George's Respiratory Questionnaire (SGRQ), previously validated for use in Brazil, was used as a validation criterion. Results: The test-retest reliability (intraclass correlation coefficient) of the PFSDQ-M was 0.93, 0.92 and 0.90 for the dyspnea, fatigue and change components, respectively, compared with 0.83 for the MRC scale. Bland-Altman plots showed good test-retest concordance for the PFSDQ-M. The components of the PFSDQ-M and the MRC scale correlated significantly with all of the domains and the total score on the SGRQ (0.49 < r < 0.80; p < 0.01 for all). Conclusions: The Portuguese-language versions of the PFSDQ-M and the MRC scale proved reproducible and valid for use in patients with COPD in Brazil.

Keywords: Pulmonary disease, chronic obstructive; Activities of daily living; Validation studies.

Gastroesophageal reflux (GER) is a common cause of chest affections and symptoms, such as chronic cough, asthma, respiratory infections, pulmonary fibrosis and chest pain. Relief after medical or surgical antireflux therapy is variable. Twenty-four hour pH monitoring has been considered the gold standard for the diagnosis of gastroesophageal reflux disease (GERD). The use of 2 or more pH sensors in different locations within the esophagus is a reliable method for the diagnosis of more severe GER and enables aspiration of the airways and lungs. The purpose of this study was to determine whether the height at which reflux is detected within the esophagus is an indicator of surgical, as opposed to medical, antireflux therapy. In a series of 35 patients with cough as a sole presentation of GER the levels of reflux within the esophagus were correlated to the outcome after medical or surgical antireflux therapy. The studies and surgical procedures were performed in the affiliated hospitals of the Federal and Catholic Universities of Pelotas - RS. Chi-square and Mann-Whitney-U test were used to perform statistical analysis. The present study showed that gastroesophageal reflux into either the distal or the proximal esophagus can cause chronic cough. The height of reflux is an important predictor of response to antireflux therapy. Patients with proximal reflux treated medically do poorly. Surgical therapy is consistently associated with a good outcome, regardless of the height to which reflux occurs, particularly in patients with proximal reflux. Overall, surgical therapy provides the best outcome in all patients with chronic cough due to gastroesophageal reflux.

Keywords: Chronic cough. Gastroesophageal reflux disease. Esophageal pH monitoring.