Follow-up of a cohort of patients with noncystic fibrosis bronchiectasis for 1 year.

OBJECTIVE: The objective of this study was to evaluate the quality of life of patients with noncystic fibrosis bronchiectasis during a 1-year follow-up by using the EuroQol - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire. METHODS: A cohort study was conducted with 100 patients with noncystic fibrosis bronchiectasis and followed up with face-to-face visits or by telephone contact every 3 months for 1 year. All patients were recruited from a single referral center for bronchiectasis. At the time of recruiting and at the end of 1 year, the EQ-5D-3L questionnaire was applied to evaluate the patients' quality of life. Variables, such as exacerbation, emergency care, comorbidities, hemoptysis, colonization, and hospitalization, were assessed. RESULTS: Of the 100 patients, 99 completed the study and 72% were women. There were no marked limitations in the mobility and self-care domains during the follow-up. At the end of the follow-up, 32 patients were extremely anxious or depressed. The quality of life assessed by using EQ-5D-3L had an initial mean score of 0.545 and of 0.589 after 1 year, which was statistically significant (p=0.011). CONCLUSION: Patients with noncystic fibrosis bronchiectasis have a poor quality of life, and the EQ-5D-3L questionnaire may be a tool for monitoring patients with bronchiectasis.

Follow-up of a cohort of patients with noncystic fibrosis bronchiectasis for 1 year

SUMMARY OBJECTIVE: The objective of this study was to evaluate the quality of life of patients with noncystic fibrosis bronchiectasis during a 1-year follow-up by using the EuroQol - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire. METHODS: A cohort study was conducted with 100 patients with noncystic fibrosis bronchiectasis and followed up with face-to-face visits or by telephone contact every 3 months for 1 year. All patients were recruited from a single referral center for bronchiectasis. At the time of recruiting and at the end of 1 year, the EQ-5D-3L questionnaire was applied to evaluate the patients' quality of life. Variables, such as exacerbation, emergency care, comorbidities, hemoptysis, colonization, and hospitalization, were assessed. RESULTS: Of the 100 patients, 99 completed the study and 72% were women. There were no marked limitations in the mobility and self-care domains during the follow-up. At the end of the follow-up, 32 patients were extremely anxious or depressed. The quality of life assessed by using EQ-5D-3L had an initial mean score of 0.545 and of 0.589 after 1 year, which was statistically significant (p=0.011). CONCLUSION: Patients with noncystic fibrosis bronchiectasis have a poor quality of life, and the EQ-5D-3L questionnaire may be a tool for monitoring patients with bronchiectasis.

Mortality and comorbidities in patients with bronchiectasis over a 3-year follow-up.

To identify the risk factors associated with all-cause mortality in patients with noncystic fibrosis bronchiectasis (NCFB). This prospective cohort study included 120 adult patients with NCFB, who were regularly treated at a specialized outpatient clinic of a university hospital between January 2017 and June 2020. All patients were diagnosed using high-resolution computed tomography. Demographic and clinical data, pulmonary function tests, and the Euro-quality-of-life 5-domain 3-level questionnaire were analyzed. The factors associated with death were determined using the Cox proportional hazards model. The all-cause mortality rate at 41 months was 10.8%. Adjusted multivariate analysis showed that the main contributing predictors for mortality were female sex, smoking, diabetes, chronic obstructive pulmonary disease, emergency visits, use of antibiotics due to exacerbation, secretion color change, exacerbation, predicted forced expiratory volume in 1 second, predicted forced vital capacity, lack of respiratory physiotherapy, absence of vaccination against pneumococci, and mobility domain. Multiple factors contribute to unfavorable outcomes in patients with NCFB, and early recognition of these factors may improve care management.

The impact of healthcare-associated infections on COVID-19 mortality: a cohort study from a Brazilian public hospital

SUMMARY OBJECTIVE: This study aims to analyze the risk factors for in-hospital mortality in a cohort of patients admitted to a newly adapted intensive care unit in a public hospital in Rio de Janeiro. METHODS: This was an observational, retrospective, and descriptive study. Data were obtained from electronic medical records. Coronavirus disease 2019 (COVID-19) was diagnosed by detecting viral ribonucleic acid using reverse transcription polymerase chain reaction. Factors associated with the risk/protection from death were determined using the odds ratio and adjusted odds ratio. RESULTS: Fifty-one patients were admitted to the hospital. The median age of the patients was 63 years, 60% were male patients, and 54% were white patients. Sixty-seven percent of the patients were diagnosed with COVID-19. Sepsis at admission increased the chance of in-hospital death by 21 times (adjusted odds ratio=21.06 [0.79-555.2]; p=0.06). The strongest risk factor for death was the development of septic shock during hospitalization (adjusted odds ratio=98.56 [2.75-352.5]; p=0.01), and one in four patients had multidrug-resistant bacteria. Mechanical ventilation, vasopressors, neuromuscular blockers, and sedatives were also the risk factors for in-hospital mortality. The in-hospital mortality rate was 41%, and the mortality rate of patients on mechanical ventilation was 60%. The diagnosis of COVID-19 was not statistically related to the adverse outcomes. CONCLUSIONS: In this cohort, the strongest risk factor for in-hospital death was the development of nosocomial septic shock. Healthcare-associated infections have a significant impact on mortality rates. Therefore, to have a better outcome, it is important to consider not only the availability of beds but also the way healthcare is delivered.

Diagnostic performance of the Xpert MTB/RIF assay in BAL fluid samples from patients under clinical suspicion of pulmonary tuberculosis: a tertiary care experience in a high-tuberculosis-burden area / Desempenho diagnóstico do teste Xpert MTB/RIF em amostras de LBA de pacientes com suspeita clínica de tuberculose pulmonar: experiência na atenção terciária em uma área com alta carga de tuberculose

ABSTRACT Objective: To assess the diagnostic performance of the Xpert MTB/RIF assay, a rapid molecular test for tuberculosis, comparing it with that of AFB staining and culture, in BAL fluid (BALF) samples from patients with clinically suspected pulmonary tuberculosis (PTB) who are sputum smear-negative or produce sputum samples of insufficient quantity. Methods: This was a retrospective study of 140 cases of suspected PTB in patients who were smear-negative or produced insufficient sputum samples and were evaluated at a tertiary teaching hospital in the city of Rio de Janeiro, Brazil. All of the patients underwent fiberoptic bronchoscopy with BAL. The BALF specimens were evaluated by AFB staining, mycobacterial culture, and the Xpert MTB/RIF assay. Results: Among the 140 patients, results for all three microbiological examinations were available for 73 (52.1%), of whom 22 tested positive on culture, 17 tested positive on AFB staining, and 20 tested positive on the Xpert MTB/RIF assay. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for AFB staining were 68.1%, 96.1%, 88.2%, 87.5%, and 87.6%, respectively, compared with 81.8%, 96.1%, 90.0%, 92.4%, and 91.8%, respectively, for the Xpert MTB/RIF assay. The agreement between AFB staining and culture was 82.3% (kappa = 0.46; p < 0.0001), whereas that between the Xpert MTB/RIF assay and culture was 91.8% (kappa = 0.8; p < 0.0001). Conclusions: In BALF samples, the Xpert MTB/RIF assay performs better than do traditional methods, providing a reliable alternative to sputum analysis in suspected cases of PTB. However, the rate of discordant results merits careful consideration.

RESUMO Objetivo: Avaliar o desempenho diagnóstico do teste Xpert MTB/RIF - teste molecular rápido para tuberculose, comparando-o com o da pesquisa de BAAR e da cultura, em amostras de LBA de pacientes com suspeita clínica de tuberculose pulmonar (TBP) que apresentam baciloscopia de escarro negativa ou produzem amostras com quantidade insuficiente de escarro. Métodos: Estudo retrospectivo de 140 casos suspeitos de TBP em pacientes que apresentaram baciloscopia negativa ou produziram amostras de escarro insuficientes e foram avaliados em um hospital-escola terciário na cidade do Rio de Janeiro (RJ). Todos os pacientes foram submetidos à fibrobroncoscopia com LBA. Os espécimes de LBA foram avaliados por meio da realização de pesquisa de BAAR, cultura para micobactérias e teste Xpert MTB/RIF. Resultados: Entre os 140 pacientes, resultados de todos os três exames microbiológicos estavam disponíveis para 73 (52,1%), dos quais 22 apresentaram cultura positiva, 17, pesquisa de BAAR positiva, e 20, teste Xpert MTB/RIF positivo. A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e precisão global da pesquisa de BAAR foram de 68,1%, 96,1%, 88,2%, 87,5% e 87,6%, respectivamente, contra 81,8%, 96,1%, 90,0%, 92,4% e 91,8%, respectivamente, do teste Xpert MTB/RIF. A concordância entre a pesquisa de BAAR e a cultura foi de 82,3% (kappa = 0,46; p < 0,0001), enquanto a concordância entre o teste Xpert MTB/RIF e a cultura foi de 91,8% (kappa = 0,8; p < 0,0001). Conclusões: Em amostras de LBA, o teste Xpert MTB/RIF tem melhor desempenho do que os métodos tradicionais, fornecendo uma alternativa confiável à análise do escarro em casos suspeitos de TBP. No entanto, a taxa de resultados discordantes merece uma reflexão cuidadosa.

Defining prognosis in sarcoidosis.

Sarcoidosis is a multi-systemic granulomatous disease. Affected individuals can show spontaneous healing, develop remission with drug treatment within 2 years, or become chronically ill. Our main goal was to identify features that are related to prognosis.The study consisted of 101 patients, recruited at a single center, who were already diagnosed with sarcoidosis at the start of the study or were diagnosed within 48 months. Ninety individuals were followed-up for at least 24 months and were classified according to clinical outcome status (COS 1 to 9). Those with COS 1-4 and COS 5-9 were classified as having favorable and unfavorable outcomes, respectively. Unconditional logistic regression analyses were conducted to define which variables were associated with sarcoidosis outcomes. Subsequently, we established a scoring system to help predict the likelihood of a favorable or unfavorable outcome.Of our patients, 48% developed a chronic form of the disease (COS 5-9). Three clinical features were predictive of prognosis in sarcoidosis. We built a score-based model where the absence of rheumatological markers (1 point), normal pulmonary functions (2 points), and the presence of early respiratory symptoms manifestations (2 points) were associated with a favorable prognosis. We predicted that a patient with a score of 5 had an 86% (95% confidence interval [CI] 74%-98%) probability of having a favorable prognosis, while those with scores of 4, 3, 2, 1, and 0 had probabilities of 72% (95% CI 59-85%), 52% (95% CI 40-63%), 31% (95% CI 17-44%), 15% (95% CI 2-28%), and 7% (95% CI 0-16%) of having a favorable prognosis, respectively. Thus, our easy-to-compute algorithm can help to predict prognosis of sarcoidosis patients, facilitating their management.

Evaluation of the Small Airways in Patients with Chronic Obstructive Pulmonary Disease and Alpha-1 Antitrypsin Deficiency.

Introduction: Small airways are not evaluated with traditional pulmonary function tests. The aim of this study was to evaluate the small airways in patients with chronic obstructive pulmonary disease (COPD) with a nitrogen washout test and to verify whether there is a difference between patients with COPD due to smoking and those with COPD due to alpha-1 antitrypsin mutation. Methods: Sixteen patients with mutation in the SERPINA1 gene and 45 patients with no mutation were included in this cross-sectional study. All pulmonary function tests, including the single breath nitrogen washout test, were performed for all patients and alpha-1 antitrypsin dosage was assessed with immunonephelometry. Results: A comparison of patients with COPD due to smoking and those with COPD due to smoking and mutation revealed a significant difference in closure volume (%), which was the poorest in the mutation group. In the group with COPD and mutation, there was an inverse correlation between smoking and closure volume (%). We also verified that similar to forced expiratory volume in the first second (FEV1), the phase III slope (%) and ΔN2 750-1250 mL (%) could be used to differentiate the severity of airflow limitation. Conclusion: Our results suggest that both variables, phase III slope and the ΔN2 750-1250 mL (%), could be related to COPD severity. Therefore, alterations at the distribution of the location of the emphysema could alter the results of closer volume and that the nitrogen washout test is more sensitive when compared to traditional pulmonary function test in evaluating COPD patients.

Brazilian guidelines for the pharmacological treatment of idiopathic pulmonary fibrosis. Official document of the Brazilian Thoracic Association based on the GRADE methodology.

Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.

Translation and cultural adaptation of the Sleep Apnea Clinical Score for use in Brazil / Tradução e adaptação cultural do questionário Sleep Apnea Clinical Score para uso no Brasil

ABSTRACT Objective: To translate the Sleep Apnea Clinical Score (SACS) into Brazilian Portuguese and adapt it to the cultural setting, validating it for use as a screening method for polysomnography and as a tool to quantify the risk of obstructive sleep apnea syndrome in individuals in Brazil. Methods: The translation was performed by two professionals, with subsequent synthesis of the translations. From that version, a back-translation was prepared, revised, and compared with the original by a team of experts. As a pre-test, a consensus version was applied in 20 patients randomly selected from among those under treatment at outpatient clinics at the Piquet Carneiro Polyclinic of the State University of Rio de Janeiro, in the city of Rio de Janeiro, to assess their understanding of the questions. In the validation phase, the Brazilian-Portuguese version of the SACS was applied in 86 patients who subsequently underwent polysomnography, regardless of the SACS result. Results: The analyses of the pre-test phase showed that the SACS was easily understood by the patients. In the validation phase, the SACS showed a sensitivity of 45.3% (95% CI: 32.8-58.2%), a specificity of 90.9% (95% CI: 70.8-98.9%), a positive predictive value of 93.5% (95% CI: 79.0-98.2%), a negative predictive value of 36.4% (95% CI: 30.6-42.5%), and an accuracy of 57.0% (95% CI: 45.8-67.6%). Conclusions: The Brazilian-Portuguese version of the SACS can be used in order to assess the risk of obstructive sleep apnea syndrome.

RESUMO Objetivo: Traduzir o questionário Sleep Apnea Clinical Score (SACS) para a língua portuguesa do Brasil, adaptá-lo a nossa cultura e validá-lo para que seja utilizado como método de rastreio para a realização de polissonografia e como ferramenta para quantificar o risco de síndrome da apneia obstrutiva do sono no indivíduo. Métodos: A tradução foi realizada por dois profissionais, com posterior conciliação em uma síntese das traduções. A partir dessa versão, foi elaborada uma tradução reversa, revisada e comparada com o original por uma equipe de especialistas. A versão de consenso foi aplicada em 20 pacientes aleatoriamente selecionados de ambulatórios da Policlínica Piquet Carneiro da Universidade do Estado do Rio de Janeiro, na cidade do Rio de Janeiro (RJ), para avaliar sua compreensão (pré-teste). Posteriormente, a versão brasileira do SACS foi aplicada em 86 pacientes que realizaram polissonografia, independentemente do resultado apresentado no SACS (fase de validação). Resultados: As análises da fase pré-teste demonstraram que o questionário era facilmente compreendido pelos pacientes. Na fase de validação, o questionário demonstrou sensibilidade de 45,3% (IC95%: 32,8-58,2%), especificidade de 90,9% (IC95%: 70,8-98,9%), valor preditivo positivo de 93,5% (IC95%: 79,0-98,2%), valor preditivo negativo de 36,4% (IC95%: 30,6-42,5%) e acurácia de 57,0% (IC95%: 45,8-67,6%). Conclusões: A versão do questionário SACS traduzida para a língua portuguesa do Brasil pode ser utilizada para avaliar o risco de síndrome da apneia obstrutiva do sono.

Brazilian guidelines for the pharmacological treatment of idiopathic pulmonary fibrosis. Official document of the Brazilian Thoracic Association based on the GRADE methodology / Diretrizes brasileiras para o tratamento farmacológico da fibrose pulmonar idiopática. Documento oficial da Sociedade Brasileira de Pneumologia e Tisiologia baseado na metodologia GRADE

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.

RESUMO A fibrose pulmonar idiopática (FPI) é uma forma de pneumopatia intersticial crônica fibrosante de causa desconhecida, que acomete preferencialmente homens idosos, com história atual ou pregressa de tabagismo. Mesmo sendo uma doença incomum, ela assume grande importância devido a sua gravidade e prognóstico reservado. Nas últimas décadas, diversas modalidades terapêuticas farmacológicas foram investigadas para o tratamento dessa doença, de tal modo que conceitos clássicos vêm sendo revisados. O objetivo destas diretrizes foi definir recomendações brasileiras baseadas em evidências em relação ao emprego de agentes farmacológicos no tratamento da FPI. Procurou-se fornecer orientações a questões de ordem prática, enfrentadas pelos clínicos no seu cotidiano. As perguntas PICO (acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome [desfecho] de interesse) abordaram aspectos relativos ao uso de corticosteroides, N-acetilcisteína, tratamento medicamentoso do refluxo gastroesofágico, inibidores dos receptores da endotelina, inibidores da fosfodiesterase-5, pirfenidona e nintedanibe. Para a formulação das perguntas PICO, um grupo de especialistas brasileiros atuantes na área foi reunido, sendo realizada uma extensa revisão bibliográfica sobre o tema. As revisões sistemáticas com meta-análises previamente publicadas foram analisadas quanto à força das evidências compiladas e, a partir daí, foram concebidas recomendações seguindo a metodologia Grading of Recommendations Assessment, Development and Evaluation. Os autores acreditam que o presente documento represente um importante avanço a ser incorporado na abordagem de pacientes com FPI, objetivando principalmente favorecer seu manejo, e pode se tornar uma ferramenta auxiliar na definição de políticas públicas relacionadas à FPI.

Predominance of Th1 Immune Response in Pleural Effusion of Patients with Tuberculosis among Other Exudative Etiologies.

Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor ß1 (TGF-ß), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-ß, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-ß, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-ß, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.

IgA and IgG antibody detection of mycobacterial antigens in pleural fluid and serum from pleural tuberculous patients.

BACKGROUND: A previous study demonstrated pleural fluid (PF) IgA immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases. However, no clue on the role of IgA and IgG against this and other antigens in PF and serum concerning improved diagnosis is available. Thus, the aim of the present study was to validate PF IgA-MT10.3:MPT64 and evaluate PF and serum IgA and IgG reactivity against this protein, its peptides (F2) and single MPT64, MT10.3 and the PPE59 mycobacterial specific antigens. IgA and IgG ELISA were measured against the antigen in PLTB (n = 29) and other non-TB pleurisy (n = 39) patient samples. RESULTS: The immunodominance of PF IgA-MT10.3:MPT64 was confirmed in PLTB (86.2%) followed by PPE59 (62%), while serum IgA-F2 exhibited 51.7% sensitivity. PF and serum IgG-MT10.3:MPT64 led to 65.5 and 51.7% sensitivity, respectively. However, MT10.3 and MPT64 displayed overall lower sensitivity (≤34.5) for both antibodies. All results at 95% fixed specificity. Combinatory results indicated 93.1% sensitivity for PF IgA-MT10.3:MPT64/-PPE59 and IgA/IgG-MT10.3:MPT64 at 92.3% specificity, followed by IgA-MT10.3:MPT64/-MPT64 or /-F2 (89.6%) without jeopardizing specificity (94.9%). The combinatory results of the PF adenosine deaminase test (ADA) and IgA-MT10.3:MPT64/-F2 demonstrated the highest sensitivity (96.6%), with a specificity of 92.3%. CONCLUSIONS: The PF IgA-MT10:MPT64 immune dominance was validated in PLTB, and its combinatory results with PPE59 or MPT64 or F2 antigens as well as with IgG, are reported herein for the first time, improving their potential to assist diagnosis. Combining PF-ADA and IgA-MT10.3:MPT64/-F2 results achieved better accuracy. Moreover, serum IgG, although less accurate, displays potential beyond microbiological tests.

Alpha 1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease patients: is systematic screening necessary?

OBJECTIVE: Alpha-1-antitrypsin deficiency is a relatively prevalent, but under-diagnosed, genetic disease. The objective of this study was to assess whether the systematic screening for alpha-1-antitrypsin deficiency in all patients with chronic obstructive pulmonary disease from a tertiary service has an impact on the number of patients being diagnosed with this condition. RESULTS: Chronic obstructive pulmonary disease patients were screened for alpha-1-antitrypsin deficiency using immunonephelometry. The presence of a mutation was confirmed by molecular study of the SERPINA1 gene or by genetic sequencing, as needed. A total of 551 patients with chronic obstructive pulmonary disease were analyzed. Among these, 40 (7.2%) had some genetic mutation, while 11 (2%) had a Pi*ZZ genotype, resulting in severe respiratory illness. The systematic evaluation of chronic obstructive pulmonary disease patients revealed that screening is an effective method to diagnose alpha-1-antitrypsin deficiency. Early diagnosis may facilitate smoking cessation and initiation of treatment to maintain lung function.

Application of Venn's diagram in the diagnosis of pleural tuberculosis using IFN-γ, IP-10 and adenosine deaminase.

BACKGROUND: Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases. METHODS AND FINDINGS: Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination. CONCLUSION: IFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative results suggest further investigation.

Estimated cost of asthma in outpatient treatment: a real-world study / Estimativa de custo da asma em tratamento ambulatorial: estudo com dados de mundo real

ABSTRACT OBJECTIVE To estimate the cost of diagnosis and treatment of asthma. METHODS We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. RESULTS The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. CONCLUSIONS Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease.

RESUMO OBJETIVO Estimar o custo do diagnóstico e tratamento da asma. MÉTODOS Foi utilizada a perspectiva da sociedade. Foram incluídos por 12 meses em 2011-2012, sequencialmente, 117 indivíduos maiores de cinco anos de idade, em tratamento por asma nos Serviços de Pneumologia e Alergia-Imunologia da Policlínica Piquet Carneiro, Universidade do Estado do Rio de Janeiro. Todos realizaram duas entrevistas com seis meses de intervalo para coleta de dados, cobrindo 12 meses. As unidades de custos foram identificadas e valoradas de acordo com métodos definidos. Foi feita análise de sensibilidade e foram aplicados métodos estatísticos com nível de significância de 5% para comparações de custos entre subgrupos. RESULTADOS Cento e oito pacientes completaram o estudo, 73,8% eram mulheres. Mediana de idade foi de 49,5 anos. Rinite esteve presente em 83,3%, e mais da metade tinha sobrepeso ou obesidade. A renda familiar média foi de R$1.566,19/mês (DP = 1.503,30). A maioria dos trabalhadores e dos estudantes teve absenteísmo relacionado à asma. O custo médio anual total foi de R$2.207,99/paciente (DP = 2.220,55). O custo relacionado à asma isolada foi de R$1.984,17/paciente-ano (DP = 2.232,55). Asmáticos obesos, graves ou não controlados tiveram maiores custos em comparação aos não obesos (p = 0,001), não graves e controlados (p = 0,000). O custo direto correspondeu a 82,3% do custo total estimado. O custo com medicamentos para asma correspondeu a 62,2% dos custos diretos da asma. CONCLUSÕES Medicamentos para asma, medidas de controle ambiental e licenças de saúde prolongadas tiveram maior impacto potencial na variação do custo total. Os resultados são uma estimativa do custo do tratamento da asma em nível secundário no Sistema Único de Saúde, assumindo-se que o tratamento utilizado represente a abordagem ideal da doença.

Tomographic Aspects of Advanced Active Pulmonary Tuberculosis and Evaluation of Sequelae following Treatment.

Objectives. To evaluate tomographic changes in pulmonary tuberculosis (TB), degree of agreement among three radiologists regarding tomographic diagnoses, and sequelae following treatment. Methods. Cross-sectional and descriptive study of 74 TB patients confirmed by sputum culture and chest computed tomography before (CT1) and 6 months after (CT2) drug therapy. Results were performed by three radiologists blinded to clinical and laboratory results. Results. Main findings in CT1 included nodules indicating the presence of a tree-in-bud pattern in 93% of cases, ill-defined nodules in 84% of cases, consolidation in 77% of cases, architectural distortion in 71% of cases, cavitary lesions in 62% of cases, and ground glass opacities in 37% of cases. Airway involvement, characterized by increased thickness and dilatation of the bronchial walls, occurred in 93% of cases. Pleural involvement occurred in 54%. There was an agreement on active TB among the three radiologists in 85% of cases. The results in CT2 indicated the presence of architectural distortion in 91% of cases and cylindrical bronchiectasis in 86%. Conclusions. The study established a tomographic pattern for diagnosis of active TB characterized by the presence of airway nodules, consolidation, architectural distortion, and cavitary lesions, and an almost complete degree of agreement (Kappa) was observed among the radiologists (0.85). CT after treatment assists in defining the cure.

Quando devemos usar CI na DPOC? / When should we use IC in COPD?

Embora as diretrizes para o tratamento da doença pulmonar obstrutiva crônica (dpoc) preconizem o uso de corticoides inalatórios para os casos mais graves e, especialmente, para aqueles que apresentam exacerbações frequentes, verifica-se que o uso destes medicamentos é muito comum inclusive em casos leves e como primeira opção de tratamento. A falta de estudos robustos em pacientes com dpoc e a experiência positiva adquirida no tratamento dos pacientes com asma facilitou a disseminação do uso dos corticoides inalatórios para tratar os pacientes com doença obstrutiva devido ao fumo. Estudos posteriores demonstraram que os corticoides inalados usados isoladamente em pacientes com dpoc não só eram ineficazes, como aumentavam o risco de vários eventos adversos, especialmente a pneumonia. Atualmente, após várias revisões, o documento gold (global initiative for chronic obstructive pulmonary disease) sugere o uso de broncodilatadores combinados para o tratamento de pacientes estáveis. O corticoide inalatório pode ser usado em combinação com um broncodilatador nos pacientes com asma associada, nos que apresentam eosinofilia e naqueles que persistem com exacerbações.

Although the guidelines for the treatment of Chronic Obstructive Pulmonary Disease (COPD) advocate the use of inhaled corticosteroids for more severe cases, and especially for those with frequent exacerbations, the use of these medications is very common even in as the first treatment option. The lack of robust studies in patients with COPD and the positive experience gained in treating patients with asthma facilitated the spread of inhaled corticosteroids in the to treat patients with obstructive disease due to smoking. Subsequent studies have shown that inhaled corticosteroids used alone in COPD patients were not only ineffective, but also increased the risk of some adverse events, especially pneumonia. Currently, after several reviews, the GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) document suggests the use of combined bronchodilators for the treatment of stable patients. Inhaled corticosteroids may be used in combination with a bronchodilator in patients with associated asthma, those with eosinophilia, and those who persist with exacerbations.

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center / Tratamento da esclerose sistêmica com rituximabe: uma série de 10 casos em centro único

Abstract Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies. Objective This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center. Patients and methods We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected. Results Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease. Discussion Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment.

Resumo A esclerose sistêmica (ES) é uma doença autoimune crônica de alta morbimortalidade. Ainda que a ciclofosfamida seja eficaz, para casos graves e refratários há demanda para novos tratamentos. A terapia biológica com depleção de células B com rituximabe (RTX) demonstrou eficácia para tal demanda em estudos abertos. Objetivo Avaliar retrospectivamente todos os pacientes que fizeram uso do RTX para tratamento de ES em nosso centro. Pacientes e métodos Foram avaliados retrospectivamente todos os prontuários de pacientes com ES que fizeram uso de RTX para tratamento da ES de janeiro de 2009 a janeiro de 2015. Dados de acometimento sistêmico, cutâneo, pulmonar e laboratoriais antes e seis meses após a primeira infusão de RTX foram coletados. Resultados Dez pacientes receberam o tratamento no período de estudo e foram incluídos na presente série de casos. Todos os pacientes tinham a forma difusa da doença. Cinco pacientes tinham formas iniciais (tempo de doença menor ou igual a quatro anos) e rapidamente progressiva da doença e cinco receberam o RTX em fases tardias da doença. Houve estabilização do quadro pulmonar em ambos os grupos de pacientes e redução no escore cutâneo nos pacientes com formas iniciais da doença. Discussão Similar ao encontrado em estudos prévios, o RTX foi eficaz no tratamento de formas iniciais e rapidamente progressivas da ES. Verificamos também benefício em pacientes com longa duração da doença.

Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function.

Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is noteworthy that patterns of body fat distribution significantly influence the function of the respiratory system, likely via the direct mechanical effect of fat accumulation in the chest and abdominal regions. Weight loss caused by various types of treatment, including low-calorie diet, intragastric balloon, and bariatric surgery, significantly improves lung function and metabolic syndrome and reduces body mass index. Despite advances in the knowledge of pulmonary and systemic complications associated with obesity, longitudinal randomized studies are needed to assess the impact of weight loss on metabolic syndrome and lung function.

Update on diagnosis and treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation.