Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration> or = 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues.Keywords: alpha 1-antitrypsin; Emphysema; Pulmonary disease, chronic obstructive. ResumoA deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnós-tico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiro...

Background Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. MethodsIn this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middleincome countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42•4% vs 44•2%; absolute difference -1•69 [-9•58 to 6•11] p=0•67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H 2 O; p=0•0011). ICU mortality was higher in MICs than in HICs (30•5% vs 19•9%; p=0•0004; adjusted effect 16•41% [95% CI 9•52-23•52]; p<0•0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0•80 [95% CI 0•75-0•86]; p<0•0001).Interpretation Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status.