OBJECTIVE:Uncontrolled asthma is common among Latin American patients. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, drivers of type 2 inflammation. METHODS:This post hoc analysis of 48-96 week open-label extension TRAVERSE (NCT0213402) study assessed dupilumab 300 mg every 2 wk up to 148 wk (parent study plus extension) in patients with moderate-to-severe asthma enrolled from Latin American centers who previously completed a dupilumab asthma study (phase 2b or phase 3 QUEST). Endpoints included treatment-emergent adverse events, severe asthma exacerbations, pre-bronchodilator forced expiratory volume in 1 s (FEV1), 5-Item Asthma Control Questionnaire (ACQ-5), Asthma Quality of Life Questionnaire (AQLQ), and type 2 biomarkers. RESULTS:A total of 596 (28.9%) patients were enrolled from Latin American centers. Safety was consistent with the known dupilumab safety profile. Annualized rate of severe exacerbations remained low across patients (0.115-0.459). Improvements in pre-bronchodilator FEV1 were sustained to Week 96 (mean change from parent study baseline of 0.28-0.35 L) and in ACQ-5 and AQLQ scores to Week 48 (last assessed time-point). Patients receiving placebo during parent studies demonstrated improvements once switched to dupilumab in TRAVERSE. Patients receiving dupilumab during parent studies demonstrated further improvements in exacerbations, ACQ-5, and AQLQ. Type 2 biomarkers decreased over time. CONCLUSIONS:Consistent with results in the overall population, long-term efficacy and safety of dupilumab was observed in patients with moderate-to-severe asthma with a treatment duration of up to 148 wk, supporting the long-term benefits of dupilumab use in Latin American patients.

Objective: To describe the impact of severe asthma in a real-life cohort in Brazil, reporting on baseline clinical characteristics, access to treatment, and clinical remission under treatment with biologics. Methods: Severe asthma patients > 6 years of age were recruited from 23 centers in Brazil. Data on clinical characteristics, lung function, biomarkers, prescribed therapies, and clinical remission under treatment were collected at the baseline visit. Results: A total of 417 patients were recruited. Of the 162 adult patients, 71% had a history of hospitalization, with 31% having experienced more than two severe exacerbations in the last 12 months and 6% having experienced cardiopulmonary arrest. Allergic and eosinophilic phenotypes were the most common phenotypes in all age groups, with the T2-low phenotype being observed in 10% of the pediatric patients and in 20% of the adult patients. Only 10% of the adult patients and 1% of the pediatric patients were receiving maintenance oral corticosteroids, whereas 41% of the adult patients were under treatment with biologics, with clinical remission being achieved in 20%. Conclusions: Severe asthma in Brazil still results in a high disease burden, with less than half of the patients receiving treatment with biologics and clinical remission being achieved in a subgroup of patients treated with biologics for more than 12 months. Achieving disease control remains a major clinical and health care challenge, requiring further actions from specialists and health care providers, as well as additional studies.

Objectives To explore asthma control in patients undergoing pharmacotherapy on studies in the last 20 years in Brazil. Asthma is a chronic airway inflammation disease with a high prevalence worldwide. Even with a variety of drug treatment improvements, attaining asthma control is challenging, since it should have a personalized approach. In Brazil, studies on the prevalence of asthma control are scarce and usually from a small sample size. Data Sources A systematic review was performed to assess asthma control in Brazilian population. Terms related to "asthma", "asthma control" and "Brazil" were used in the search strategies in PubMed, BVSalud, Embase and Cochrane Library, including Brazilian Journal of Allergy and Immunology as data sources. A narrative synthesis was performed to report key outcome. Study Selections In total, 23 studies were included. Most of them were conducted in the Southeastern and Northeast regions, in a short duration. Results Pediatric and non-pediatric population were assessed, with a higher proportion of female. In pediatric population, those with poorly controlled asthma usually had severe or persistent disease. In elderly, an increased asthma severity was found, although proper treatment might be effective. Most studies (70%) also described exacerbations, hospitalizations (48%), quality of life (39%), and emergency visits (30%). Despite heterogeneity of outcomes and population, studies show an important prevalence of uncontrolled asthma even in patients being treated, with better disease control with treatment improvements. Conclusions Studies in Brazil have shown that asthma control remains a challenge and there is still a need for improvement on disease management.

Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Registries are a valuable tool in the research of rare conditions such as PAH. Moreover, the risk assessment strategy has been validated in European and North American registries and has been reported to provide an accurate prediction of mortality and the clinical advantage of reaching low-risk status. However, there is no available data from Brazil. Thus, the aim of the present study was to describe the characteristics of a sample of PAH from Southern Brazil and to retrospectively validate the risk assessment at our population. The RESPHIRAR is a retrospective and multicentric registry on pulmonary hypertension. With a join collaboration from nine centers in Southern Brazil, demographics, clinical presentation, and hemodynamics data of PAH were collected between 2007 and 2017. Moreover, the REVEAL 2.0 and REVEAL 2.0 Lite risk assessments were validated in our population. Overall, 370 PAH patients were included in the present study. Patients were predominantly female (78.5%) and had a mean age of 41.8 +/- 18.8 years. Most patients (33.4%) had idiopathic PAH, 30.2% had PAH associated with congenital heart disease, and 23.5% had PAH associated with connective tissue disease. The low-risk group showed significantly lower mortality than the intermediated- or high-risk group at diagnosis (p < 0.05). In conclusion, our data suggest that REVEAL 2.0 and REVEAL 2.0 Lite risk assessments can predict mortality risk in PAH patients in Southern Brazil.

Asthma is characterized by respiratory symptoms such as shortness of breath, wheezing, cough, and chest tightness that are often worse at night and may vary over time and intensity, together with variable airflow obstruction.Symptoms can be triggered by viral infections, exposure to allergens, smoke, exercise, changes in weather, and irritants.Detailed anamnesis and physical examination support asthma diagnosis.Additionally, documented expiratory airflow limitation and excessive variability in lung function corroborate the diagnosis 5 .Symptoms of asthma are similar in pregnant and nonpregnant patients.However, if a pregnant woman complains of shortness of breath or chest tightness, the asthma diagnosis should be carefully made based only on her symptoms 6 .Frequently, pregnant women complain of shortness of breath or chest tightness (approximately two-thirds) during the pregnancy period 7 .During pregnancy, several physiological and structural changes can contribute to a sensation of dyspnea, such as the dilated uterus, elevated diaphragm, and increased anteroposterior and transverse diameter of the thorax.Such changes are compensated by a reduction of thoracic compliance, and as a result, the functional residual capacity (FRC) and total lung function (TLC) decrease by 20 and 5%, respectively 8 .Spirometry parameters such as forced expiratory volume in first second (FEV1), forced vital capacity (FVC), and FEV1/ FVC do not change during pregnancy compared to reference values in the nonpregnancy period.Spirometry may help asthma diagnosis in pregnant women by detecting reversible airway obstruction and helping monitor response to treatment.Bronchial provocation tests are not advisable to be carried out in pregnant women to prevent maternal hypoxia and fetal distress.

Objective: To assess the prevalence of the eosinophilic and allergic phenotypes of severe asthma in Brazil, as well as to investigate the clinical characteristics of severe asthma patients in the country. Methods: This was a cross-sectional study of adult patients diagnosed with severe asthma and managed at specialized centers in Brazil. The study was conducted in 2019. Results: A total of 385 patients were included in the study. Of those, 154 had a blood eosinophil count > 300 cells/mm3 and 231 had a blood eosinophil count of = 300 cells/mm3. The median age was 54.0 years, and most of the patients were female, with a BMI of 29.0 kg/m2 and a history of allergy (81.6%). The prevalence of patients with a blood eosinophil count > 300 cells/mm3 was 40.0% (95% CI: 35.1-44.9), and that of those with a blood eosinophil count > 300 cells/mm3 and a history of allergy was 31.9% (95% CI: 27.3-36.6). Age and BMI showed positive associations with a blood eosinophil count > 300 cells/mm3 (OR = 0.97, p < 0.0001; and OR = 0.96, p = 0.0233, respectively), whereas the time elapsed since the onset of asthma symptoms showed an increased association with a blood eosinophil count > 300 cells/mm3 (OR = 1.02, p = 0.0011). Conclusions: This study allowed us to characterize the population of severe asthma patients in Brazil, showing the prevalence of the eosinophilic phenotype (in 40% of the sample). Our results reveal the relevance of the eosinophilic phenotype of severe asthma at a national level, contributing to increased effectiveness in managing the disease and implementing public health strategies.

Introduction: Asthma has a variety of respiratory symptoms, changing over time and in intensity, with variable airflow limitation. Despite that, many patients do not recognize asthma as a lung disease and some report that they ignore it in order to feel normal and accepted. Objective: to study patient’s perception of asthma as a lung disease. Methods: A cross-sectional, non-interventional study was performed to evaluate data of all individuals who performed spirometry and answered a standardized respiratory symptoms questionnaire, from October 2017 to March 2020 at an University Hospital. Only the data from subjects who answered they had no lung disease were evaluated. Their answers for asthma diagnosis and respiratory symptoms (wheeze, shortness of breath, cough, sputum) and treatments were analyzed and compared. Results: 1073 subjects were included, 152 were excluded due to inconsistent data and 921 subjects were analyzed. 467 (50,7%) subjects denied any lung disease, but 167 (18,1%) of them also said they had asthma. These patients had significantly more cough (55,1%), wheeze (47,9%), used more inhaled medication (68,8%) and had worse lung function (pre bronchodilatador FEV1) than subjects who denied both any lung disease and asthma. Conclusion: 18,1% of the patients who denied having any lung disease also confirmed an asthma diagnosis at the same time. Those subjects had significantly more respiratory symptoms and used more inhaled medication compared to those without asthma. There is a need for patient´s education in asthma, since the lack of its recognition as a chronic lung disease might contribute to less adherence to the treatment, a greater risk of exacerbations and even mortality.

Advances in the understanding that severe asthma is a complex and heterogeneous disease and in the knowledge of the pathophysiology of asthma, with the identification of different phenotypes and endotypes, have allowed new approaches for the diagnosis and characterization of the disease and have resulted in relevant changes in pharmacological management. In this context, the definition of severe asthma has been established, being differentiated from difficult-to-control asthma. These recommendations address this topic and review advances in phenotyping, use of biomarkers, and new treatments for severe asthma. Emphasis is given to topics regarding personalized management of the patient and selection of biologicals, as well as the importance of evaluating the response to treatment. These recommendations apply to adults and children with severe asthma and are targeted at physicians involved in asthma treatment. A panel of 17 Brazilian pulmonologists was invited to review recent evidence on the diagnosis and management of severe asthma, adapting it to the Brazilian reality. Each of the experts was responsible for reviewing a topic or question relevant to the topic. In a second phase, four experts discussed and structured the texts produced, and, in the last phase, all experts reviewed and approved the present manuscript and its recommendations.

ABSTRACT The pharmacological management of asthma has changed considerably in recent decades, as it has come to be understood that it is a complex, heterogeneous disease with different phenotypes and endotypes. It is now clear that the goal of asthma treatment should be to achieve and maintain control of the disease, as well as to minimize the risks (of exacerbations, disease instability, accelerated loss of lung function, and adverse treatment effects). That requires an approach that is personalized in terms of the pharmacological treatment, patient education, written action plan, training in correct inhaler use, and review of the inhaler technique at each office visit. A panel of 22 pulmonologists was invited to perform a critical review of recent evidence of pharmacological treatment of asthma and to prepare this set of recommendations, a treatment guide tailored to use in Brazil. The topics or questions related to the most significant changes in concepts, and consequently in the management of asthma in clinical practice, were chosen by a panel of experts. To formulate these recommendations, we asked each expert to perform a critical review of a topic or to respond to a question, on the basis of evidence in the literature. In a second phase, three experts discussed and structured all texts submitted by the others. That was followed by a third phase, in which all of the experts reviewed and discussed each recommendation. These recommendations, which are intended for physicians involved in the treatment of asthma, apply to asthma patients of all ages.

OBJECTIVE:To compare the right atrium (RA) area and right ventricular ejection fraction (RVEF) with other known prognostic markers in patients with pulmonary arterial hypertension (PAH).MATERIALS AND METHODS:This was a retrospective study of 74 patients diagnosed with PAH by right heart catheterization at a referral center between January 2018 and May 2018. All of the patients underwent cardiac magnetic resonance imaging (MRI) within 3 months of the right heart catheterization (RHC), as well as undergoing echocardiography, a 6-minute walk test, and determination of the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) within a month of the RHC. We attempted to determine whether the cardiac MRI-derived RA area correlated with ions between RVEF and RA area measured by that determined by echocardiography, as well as whether the cardiac MRI-derived RA area and RVEF correlated with the 6-minute walk distance and NT-proBNP level.RESULTS:The MRI-derived RA area demonstrated a weak correlation with the pulmonary vascular resistance measured by RHC (r = 0.268; p = 0.055) and a moderate correlation with the NT-proBNP (r = 0.429; p = 0.003). All correlations between clinical characteristics and the RVEF were statistically significant. In the univariate linear analysis, the RVEF showed stronger correlations with the clinical characteristics than did the RA area.CONCLUSION:In patients with PAH, cardiac MRI-derived RVEF appears to correlate more strongly with other prognostic factors than does RA area.

Despite the concept of more forms of invasive disease be related to penicillin-resistant Streptococcus pneumoniae, in the general population the clinical outcomes are not worse than for penicillin susceptible disease. However, specifically for immunocompromised patients, it is still unknown if the penicillin-resistant pneumococcal infection related clinical outcomes are worse. Purpose: To compare the clinical outcomes of penicillin-resistant S. pneumoniae infections between immunocompromised (IC-) and immunocompetent (IC+) patients. Methods: A cross-sectional study was performed in a tertiary hospital, between Sep/2011 and Apr/2018. All patients with a positive culture to S. pneumoniae isolated from blood, cerebrospinal fluid, abdominal fluid or synovial fluid were evaluated. Clinical outcomes of mechanical ventilation, ICU admission and death were compared between IC- and IC+. For the study purpose, IC+ patients were defined as having at least one of the following: HIV+, active significant hematological, oncological or liver diseases, chronic renal failure, diabetes, pregnancy. Results: 133 patients were included (75 male, mean age 51,6 years). Pneumonia was the most frequent diagnosis (82,7%), and blood culture was the most frequent source. 89 (66,9%) subjects were in the IC- group. Penicillin-resistant S. pneumoniae overall prevalence was 8,3% (11), while 6,7% (6) in the IC- group, and 11,4% (5) in the IC+ group. There was no significant difference in evaluated clinical outcomes between the IC- or IC+ patients (p>0,05). Conclusion: There was no association between penicillin-resistant S. pneumoniae and worse clinical outcomes in the immunocompromised patients.

Introduction: Smokers without airway obstruction (FEV1 / FVC> 0.7) per current guidelines, should not receive the COPD diagnosis or treatment, even if symptomatics. Aim: to evaluate the prevalence enfisema by CT scan, and also commom respiratory symptoms and DLCO findings in smokers. Methods: Data from smokers with FEV1/CVF > 0.7 per spirometry and with a previous CT scan were reviewed from Oct 2017 to Jan 2018. By the time of spirometry, smokers routinely answered about respiratory symptoms. Results: 256 smokers were evaluated and 80 had chest CT scan. 17 (21.3%) had emphysema, with a mean (±SD) DLCO of 51.9± 13.4. Non emphysema smokers had a mean (±SD) DLCO of 61.1 ± 16.9. The smoking load was different between groups: mean (±SD) of 36.7 ± 13.9 in emphysematous versus 10.4 ± 15.4 in non emphysema. Respiratory symptoms were the same between groups, with exception of sputum, more commom in enphysematous. Conclusion: 21,3% of the smokers had emphysema despite normal FEV 1 / FVC ratio. DLCO showed only a trend to be lower in emphysema smokers.

Omalizumab treatment improves control in a specific subset of severe asthmatics. Active smoking is a well known factor that impairs asthma control and also omalizumab response, but impact of passive smoking was not yet been stablished. Aim: investigate if passive smoking affects omalizumab response to treatment. Methods: Data from adult severe asthmatics, non-active smokers, who had omalizumab between Jan 2008 and Jan 2018 at our site were retrospectively analyzed. Asthma control was routinely evaluated by Asthma Control Test (ACT) since first treatment and then every month, as well as data from passive smoking, exacerbations, hospitalizations and emergency visits in previous year. Data from the time of first omalizumab use was compared with the last available. Results: 14 patients were evaluated: 78,6% female, mean age 46,2 years-old, mean omalizumab treatment 2,6 years. 64,3% had passive smoking exposure at the beginning of treatment. Both passive smokers and non-smokers improved ACT scores after treatment: from 8,8 (±3,1) to 21 (±3,2) in non-smokers and from 14,78 (±4,7) to 18,4 (±4,9) in passive smokers. However, in non-smokers, the magnitude of ACT scores improvement was greater than in passive smokers: 12,2 (±4,6) versus 3,7 (±3,3), p<0,05. Passive smokers had a trend to higher initial exacerbations rates, hospitalizations and emergency visits than non-smokers: respectively 15,0 (±14,1), 2,4 (±0,1), 10,7 (±8,7) versus 6,0 (±4,7), none, 5 (±3,7). After treatment both groups improved and there was no difference between those rates. Conclusion: Non-smokers had a higher magnitude of response to omalizumab than passive smokers based on ACT, despite a worse initial score, but both groups improved after treatment.

OBJECTIVE:To evaluate the quantitative computed tomography (QCT) phenotypes, airflow limitations, and exacerbation-like episodes in heavy smokers in Southern Brazil. METHODS:We enrolled 172 smokers with a smoking history ≥30 pack-years who underwent pulmonary function tests (PFTs) and CT scan for lung cancer screening. Patients were classified regarding airflow limitation (FEV1/FVC <0.7 forced expiratory volume in 1 second/forced vital capacity) and the presence of emphysema on the QCT. The QCT were analyzed in specialized software and patients were classified in two disease-predominant phenotypes: emphysema-predominant (EP) and non-emphysema-predominant (NEP). EP was determined as ≥6% of percent low-attenuation areas (LAA%) with less than -950 Hounsfield units. NEP was defined as having a total LAA% of less than 6%. RESULTS:Most of our patients were classified in the EP phenotype. The EP group had significantly worse predicted FEV1 (60.6 ±22.9 vs. 89.7 ±15.9, p <0.001), higher rates of airflow limitation (85.7% vs. 15%; p <0.001), and had more exacerbation-like episodes (25.8% vs. 8.3%, p <0.001) compared to the NEP group. Smoking history, ethnicity, and BMI did not differ between the groups. The total LAA% was the QCT parameter with the strongest correlation to FEV1 (r = -0.669) and FEV1/FVC (r = -0.787). CONCLUSIONS:Heavy smokers with the EP phenotype on QCT were more likely to have airflow limitation, worse predicted FEV1, and a higher rate of exacerbation-like episodes than those with the NEP phenotype. Approximately 23% of patients with no airflow limitation on PFTs were classified in EP phenotype.

CTEPH treatment might modify physical functioning and quality of life (QoL), specially surgery. If surgery is not feasible, riociguat treatment might be an alternative, but its impact in QoL has inconsistent results (Ghofrani HA et al. ERJ 2013; 42:P3418). Objectives: To evaluate impact of riociguat in physical functioning and QoL of inoperable CTEPH patients treated at our site. Methods: Patients with confirmed diagnosis that received routine indication of riociguat between Sep and Nov 2016 were included. QoL was evaluated through SF-36 Heath Survey and physical functioning through 6 min walk test (6MWT). Evaluations were performed by the time of prescription and after every 3 (+/-1) months. Results: Riociguat was prescribed for 3 cases at our center and follow up evaluations were obtained from 2 of them: patients were female, mean age was 64 years old. There was a consistent improvement of 6MWT distance (64m) during 5 months of treatment for the first subject and no change for the second subject after 3 months. Interestingly, for both subjects mean Borg dyspnea scale results improved (change of 3 points for pre and 5 points for post 6MWT). Mean peripheral oxygen (O2) saturation increased for the first subject (from 94 to 98% pre test, from 92 to 96% post), but did not change for the second one (kept 93% pre and 92% post 6MWT). There was no change in any physical or mental health scale domain of the SF-36 for both subjects. Conclusion: Riociguat induced an improvement in physical functioning (increased/stable distance and saturation, associated with reduced Borg score), but this positive outcome was not associated with improvement of QoL, measured by the SF-36.

BACKGROUND:Mortality from asthma increased during the last decades but is now declining in some countries. Little is known about this trend in Brazil.OBJECTIVE:The objective of the study was to determine the trends in asthma mortality in Southern Brazil.METHODS:We reviewed death certificates of 566 people in the state of Rio Grande do Sul, Brazil, between 5 and 39 years of age in whom asthma was reported to be the underlying cause of death during the period of 1981-2003. Population data were available in 5-year age groups. Mortality rates were submitted to linear and quadratic regression procedures.RESULTS:Among children and teenagers (5-19 years), there were 170 asthma deaths, ranging from 4 to 13 deaths each year with rates of 0.154/100,000 to 0.481/100,000. In young adults (20-39 years), 396 asthma deaths occurred, ranging from 9 to 32 each year, with rates from 0.276/100,000 to 1.034/100,000. There was an initial increase in rates, with later stabilization, and then the start of a decline beginning in the late 1990s and the early part of this decade. This trend occurred in both age subgroups examined but was more evident in males.CONCLUSIONS:Asthma mortality in southern Brazil remains low and appears to be decreasing after reaching a peak in the mid-1990s. The reason for these trends remains unknown.