Objective: To characterize clinical phenotypes of severe asthma. Methods: A total of 111 patients were retrospectively evaluated at a specialized outpatient clinic. A systematic protocol for patient evaluation and follow-up was applied. Treatment compliance and control of the disease at the end of follow-up were defined by clinical and functional data. Patients who did not meet asthma control criteria after six months despite compliance with treatment and correct use of medication were characterized as treatment-resistant. Phenotypes were determined by factorial analysis and compared using various tests. Results: At the end of follow-up, 88 patients were considered treatment compliant and 23 were considered noncompliant. Factorial analysis of the compliant patients identified four phenotypes: phenotype 1 (28 patients) comprised patients who were treatment-resistant, more often presenting nocturnal symptoms and exacerbations, as well as more often using rescue bronchodilators; phenotype 2 (48 patients) comprised patients with persistent airflow limitation, lower ratios of forced expiratory volume in one second/forced vital capacity at baseline, more advanced age and longer duration of symptoms; phenotype 3 (42 patients) comprised patients with allergic rhinosinusitis who were nonsmokers and presented predominantly reversible airflow obstruction; and phenotype 4 (15 patients) comprised cases with a history of aspirin intolerance to acetylsalicylic acid associated with near-fatal asthma. Conclusions: A significant number of patients with severe asthma are noncompliant with treatment. Although many patients with severe asthma have persistent airflow obstruction, the most relevant clinical phenotype comprises patients who are resistant to the typical treatment.

Keywords: Asthma; Asthma/prevention & control; Asthma/treatment.

Objective: Studies characterizing asthma phenotypes have predominantly included adults or have involved children and adolescents in developed countries. Therefore, their applicability in other populations, such as those of developing countries, remains indeterminate. Our objective was to determine how low-income children and adolescents with asthma in Brazil are distributed across a cluster analysis. Methods: We included 306 children and adolescents (6-18 years of age) with a clinical diagnosis of asthma and under medical treatment for at least one year of follow-up. At enrollment, all the patients were clinically stable. For the cluster analysis, we selected 20 variables commonly measured in clinical practice and considered important in defining asthma phenotypes. Variables with high multicollinearity were excluded. A cluster analysis was applied using a two-step agglomerative test and log-likelihood distance measure. Results: Three clusters were defined for our population. Cluster 1 (n = 94) included subjects with normal pulmonary function, mild eosinophil inflammation, few exacerbations, later age at asthma onset, and mild atopy. Cluster 2 (n = 87) included those with normal pulmonary function, a moderate number of exacerbations, early age at asthma onset, more severe eosinophil inflammation, and moderate atopy. Cluster 3 (n = 108) included those with poor pulmonary function, frequent exacerbations, severe eosinophil inflammation, and severe atopy. Conclusions: Asthma was characterized by the presence of atopy, number of exacerbations, and lung function in low-income children and adolescents in Brazil. The many similarities with previous cluster analyses of phenotypes indicate that this approach shows good generalizability.

Keywords: Asthma/classification; Asthma/etiology; Child; Adolescent.

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.

Keywords: Keywords: Asthma; Phenotype; Biological products.

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.

Keywords: Asthma; Epidemiology; Eosinophils; Phenotype; Allergy and immunology.

Objective: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). Methods: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. Results: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. Conclusions: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

Keywords: Arthritis, rheumatoid; Lung diseases, interstitial; Spirometry; Radiography, thoracic; Airway ob-struction.

Objective: To describe the clinical features and to identify factors associated with significant severe asthma in samples of patients followed in a reference center in Salvador. Methods: A cross-sectional study of 473 adults, regularly followed in the "Asthma Control Program" in Bahia (Programa de Controle da Asma e da Rinite Alérgica na Bahia (ProAR)), reassessed systematically between 2013 and 2015. The patients were admitted for meeting previous criteria of severe asthma and were reclassified according to the most current definition proposed by a joint document of the "European Respiratory Society/American Thoracic Society" (ERS/ATS) (ERS/ATS 2014). Results: Only 88/473 (18%) were reclassified as having severe asthma by ERS/ATS criteria (SA-ERS/ATS). Among these patients, 87% were women, 48% obese, with a median Body Mass Index (BMI) of 29 kg·m2 (IQ 26-34), furthermore, 99% had symptoms of chronic rhinitis and 83% had symptoms of Gastroesophageal Reflux Disease (GERD). None of the 88 patients claimed to be current smokers. The most frequently corticosteroids were beclomethasone dipropionate (BDP) (88%) and budesonide (BUD) (69%). The majority of the evaluations reported adequate adherence (77%), however, the minority (0,6%) detected serious errors in inhalation techniques. The median Forced Expiratory Volume (FEV1) associated with post-bronchodilator test (post-BD) was 67% predicted (IQ 55-80). The median number of eosinophils in the peripheral blood was lower in patients with SA-ERS/ATS (258 cells/mm3 (IQ 116-321) than in the other patients studied [258 cells/mm3 (IQ 154-403)]. Gastroesophageal reflux symptoms were associated with a higher severity [OR = 2.2 95% CI (1.2-4.2)]. Conclusion: In this group of patients, symptoms of GERD were associated with SA-ERS/ATS and eosinophil count > 260 cells/mm3 were associated 42% with less chance SA-ERS/ATS

Keywords: Asthma; Gastroesophageal reflux disease (GERD); Eosinophils; Biomarkers.

Objective: Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. Methods: This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. Results: Over time, the use of inhaled corticosteroids and long-acting β2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. Conclusions: Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.

Keywords: Status asthmaticus; Asthma/therapy; Hospitalization.

Objective: To evaluate the association between degree of asthma control and health-related quality of life in patients with moderate or severe asthma. Methods: This was a descriptive observational study involving 59 outpatients with moderate or severe asthma under treatment at the Asthma Outpatient Clinic of the Federal University of Ceará Walter Cantídio University Hospital, in the city of Fortaleza, Brazil. The patients were evaluated regarding sociodemographic and clinical characteristics, as well as spirometric parameters. The asthma control status was assessed using the asthma control test (ACT), and quality of life was assessed using the Saint George's Respiratory Questionnaire (SGRQ). Results: The mean age of the patients was 55.0 ± 12.4 years, and 76.3% were female. The ACT score showed statistically significant negative correlations with all SGRQ scores: total (r = −0.72); symptoms (r = −0.78); activity (r = −0.67); and impact (r = −0.68). Multiple regression analysis showed that the most robust predictive variables for SGRQ total score were ACT score (coefficient = −3.18; 95% CI: −4.14 to −2.23) and duration of disease (coefficient = −0.29; 95% CI: −0.54 to −0.03). The ACT score also explained the linear variation of the SGRQ domains: symptoms (coefficient = −3.41; 95% CI: −4.45 to −2.37); activity (coefficient = −3.07; 95% CI: −4.57 to −1.57); and impact (coefficient = −2.68; 95% CI: −3.71 to −1.65). Conclusions: The degree of asthma control appears to have a significant impact on health-related quality of life.

Keywords: Asthma/prevention and control; Quality of life; Questionnaires.

Objective: To identify, characterize, and quantify associations of various factors with quality of life (QoL) in patients with asthma, according to the pharmacotherapy employed. Methods: This was a cross-sectional study involving 49 patients (≥ 18 years of age) with severe uncontrolled or refractory asthma treated at a specialized outpatient clinic of the Brazilian Unified Health Care System, regularly using high doses of inhaled corticosteroids (ICs) or other medications, and presenting comorbidities. At a single time point, QoL was assessed with the Asthma Quality of Life Questionnaire (AQLQ). The overall AQLQ score and those of its domains were correlated with demographic variables (gender and age); Asthma Control Questionnaire score; pharmacotherapy (initial IC dose, inhaler devices, and polytherapy); and comorbidities. Results: Better AQLQ scores were associated with asthma control-overall (OR = 0.38; 95% CI: 0.004-0.341; p < 0.001), "symptoms" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001), and "emotional function" domain (OR = 0.086; 95% CI: 0.016-0.476; p = 0.001)-and with IC dose ≤ 800 µg-"activity limitation" domain (OR = 0.249; 95% CI: 0.070-0.885; p = 0.029). Worse AQLQ scores were associated with polytherapy-"activity limitation" domain (OR = 3.651; 95% CI: 1.061-12.561; p = 0.036)-and number of comorbidities ≤ 5-"environmental stimuli" domain (OR = 5.042; 95% CI: 1.316-19.317; p = 0.015). Conclusions: Our results, the importance of this issue, and the lack of studies taking pharmacotherapy into consideration warrant longitudinal studies to establish a causal relationship between the identified factors and QoL in asthma patients.

Keywords: Asthma; Asthma/drug therapy; Quality of life; Medication therapy management.

Background: This study evaluated the perception of airway obstruction in moderate to severely asthmatic outpatients and the efficiency of chest auscultation in identifying airflow limitation. Methods: 33 subjects were evaluated at seven weekly visits by using symptoms scores determined by visual analogue scales (VAS, 0-100 mm), a clinical index of bronchial hyperreactivity (1-10), the clinical classification of asthma severity (GINA, 1-4) and a thoracic auscultation score (TAS, 0-5), spirometry and peak expiratory flow (PEF), which were correlated by the coefficient of Spearman. Patients were classified as perceivers (-1 £ r < 0) or nonperceivers (0 £ r £ 1) by correlations between VAS for dyspnoea and FEV1. A correlation between auscultation and bronchial obstruction was considered accurate when a r £ -0.5 (TAS vs. FEV1) was found. Results: Seventeen asthmatic patients (51.5%) did not accurately perceive the degree of their airways obstruction (nonperceivers). No clinical characteristics distinguished the groups. Only 39.4% of the individual correlations between TAS and FEV1 indicated accurate discrimination by auscultation. Severe asthma was not associated with inaccurate auscultation nor with malperception in this study. Conclusions: A significant proportion of this sample of asthmatic patients did not accurately perceive their own airway obstruction. Moreover, chest examination was shown to be an unsuitable discriminator of airflow limitation in moderate to severe stable asthmatics in an outpatient clinic.

Keywords: Asthma. Airway obstruction. Auscultation. Lung obstructive diseases.

Objective: To evaluate oral health-related quality of life (OHRQoL) among individuals with severe asthma, comparing it with that observed among individuals with mild-to-moderate asthma and individuals without asthma. Methods: We conducted a cross-sectional study of 125 individuals: 40 with severe asthma; 35 with mild-to-moderate asthma; and 50 without asthma. We calculated the decayed, missing, and filled teeth (DMFT) index, as well as the Periodontal Screening and Recording index, and determined the stimulated salivary flow rate. We applied three structured questionnaires: the 14-item Oral Health Impact Profile (OHIP-14); the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2); and the Work Ability Index (WAI). Results: Periodontitis and reduced salivary flow were both more common in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups. In addition, the WAI scores were lower in the severe asthma group than in the mild-to-moderate asthma and no-asthma groups, as were the scores for all SF-36v2 domains. The individuals with severe asthma also scored lower for the OHIP-14 domains than did those without asthma. Although the mean DMFT index did not differ significantly among the groups, the mean number of missing teeth was highest in the severe asthma group. Strong correlations between the SF-36v2 Component Summaries and poorer OHRQoL were only observed in the severe asthma group. Conclusions: Severe asthma appears to be associated with poorer oral health, poorer OHRQoL, a lower WAI, and lower scores for SF-36v2 domains.

Keywords: Oral health; Periodontal diseases; Asthma.

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.

Keywords: Asthma/therapy; Asthma/drug therapy; Asthma/prevention & control; Antibodies, monoclonal, humanized.

Objective: To evaluate the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma (SEA) in a real-world clinical setting. Methods: This retrospective, observational cohort study included data from 45 SEA patients who initiated mepolizumab treatment, with 41 completing a 12-month follow-up. Demographic, clinical, and laboratory data-including exacerbation rates, forced expiratory volume in one second (FEV1), Asthma Control Test (ACT) and CARAT scores, and blood eosinophil counts-were extracted from patient medical records. Paired statistical tests were used to compare pre- and post-treatment outcomes, with significance set at p < 0.05. Results: Mepolizumab therapy was associated with an 81% reduction in annual exacerbation rates (from 2.68 to 0.51 events; p < 0.001) and a 21.6% improvement in FEV1 (from 1.71 L to 2.08 L; p < 0.001). ACT scores increased significantly from 11.91 to 21.29 (p < 0.001), with 73.2% of patients achieving well-controlled asthma (ACT = 20). CARAT scores also showed significant improvement, reflecting better control of both asthma and rhinitis symptoms. Blood eosinophil counts decreased by 64% (from 525.9 to 189.4 cells/µL; p < 0.001). Overall, the treatment was well tolerated, with only one discontinuation due to a mild headache. Conclusion: In this real-world cohort, mepolizumab significantly reduced exacerbation frequency, improved lung function and symptom control, and lowered eosinophil levels over 12 months. These findings support its use as an effective and safe therapeutic option for managing severe eosinophilic asthma.

Keywords: Mepolizumab, Eosinophilic asthma, Severe asthma.

Objective: To investigate the impact of impaired pulmonary function on patient-centered outcomes after hospital discharge due to severe COVID-19 in patients without preexisting respiratory disease. Methods: This is an ongoing prospective cohort study evaluating patients (> 18 years of age) 2-6 months after hospital discharge due to severe COVID-19. Respiratory symptoms, health-related quality of life, lung function, and the six-minute walk test were assessed. A restrictive ventilatory defect was defined as TLC below the lower limit of normal, as assessed by plethysmography. Chest CT scans performed during hospitalization were scored for the presence and extent of parenchymal abnormalities. Results: At a mean follow-up of 17.2 ± 5.9 weeks after the diagnosis of COVID-19, 120 patients were assessed. Of those, 23 (19.2%) reported preexisting chronic respiratory diseases and presented with worse lung function and exertional dyspnea at the follow-up visit in comparison with their counterparts. When we excluded the 23 patients with preexisting respiratory disease plus another 2 patients without lung volume measurements, a restrictive ventilatory defect was observed in 42/95 patients (44%). This subgroup of patients (52.4% of whom were male; mean age, 53.9 ± 11.3 years) showed reduced resting gas exchange efficiency (DLCO), increased daily-life dyspnea, increased exertional dyspnea and oxygen desaturation, and reduced health-related quality of life in comparison with those without reduced TLC (50.9% of whom were male; mean age, 58.4 ± 11.3 years). Intensive care need and higher chest CT scores were associated with a subsequent restrictive ventilatory defect. Conclusions: The presence of a restrictive ventilatory defect approximately 4 months after severe COVID-19 in patients without prior respiratory comorbidities implies worse clinical outcomes.

Keywords: Post-acute COVID-19 syndrome; Respiratory function tests; Exercise test; Quality of life; Follow-up studies.

Objective: To evaluate the capacity of the criteria described in Complementary Directive SAS/MS 12, issued on November 12, 2002, to identify patients with severe asthma, describing and comparing clinical, functional and treatment data of such patients. Methods: This was a nested case-control study using a structured database for adult asthma outpatients. We defined cases as asthma patients who met the inclusion criteria described in the directive, defining controls as those who did not. We collected and compared data related to the following: demographic characteristics; history of asthma; medications in use; comorbidities; history of tobacco use; number of exacerbations within the last 12 months, asthma-related hospitalizations and intensive care unit admissions within the last 12 months; spirometry; and sputum cytology. Results: The case and control groups consisted of 29 and 31 patients, respectively. The number of asthma exacerbations and emergency room visits within the last 12 months, as well as the number of patients that received at least one pulse of oral corticosteroids, was significantly higher in the case group than in the control group. In addition, prebronchodilator FVC was lower among the cases than among the controls. Furthermore, cytology revealed that eosinophil counts were significantly higher in the induced sputum of cases than in that of controls. Conclusions: The criteria described in the directive are suited to stratifying patients with severe asthma.

Keywords: Asthma; Budesonide; Combined modality therapy.