Laura Maria de Lima Belizário Facury Lasmar

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.

Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a ß2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Objective: To evaluate the effectiveness of home visits in a group of children and adolescents with severe asthma by using the inhalation technique score and adherence rates to drug treatment. Method: A 12-month randomized controlled trial involving patients aged between three and 17 years under regular follow-up treatment at a pediatric pulmonology outpatient clinic of a university hospital in southeastern Brazil. A group of patients received only outpatient consultations and the other group received home visits from nurses in addition to outpatient consultations. The differences between groups were analyzed through the outcomes of inhalation technique scores and treatment adherence rate. Results: Participation of 29 patients. In the intervention group, there was a statistically significant increase in inhalation technique scores (p<0.05) and elimination of critical errors between the first and the second evaluation, and results were maintained in the third evaluation. In the control group, there were no significant changes in inhalation technique scores. Rates of adherence to drug treatment in both groups did not rise. Conclusion: Home visits were effective for improving inhalation technique scores in patients with severe asthma. Brazilian Registry of Clinical Trials: RBR-8GZWZP.

In severe asthma, high doses of inhaled corticosteroids (ICS) are used in order to achieve clinical and functional control. This study aimed to evaluate lung function in outpatients (children and adolescents) with severe asthma in Brazil, all of whom were treated with high doses of ICS. We evaluated all spirometry tests together and by ICS dose: 800 and > 800 µg/day. This was a 3-year longitudinal study in which we analyzed 384 spirometry tests in 65 severe asthma patients (6–18 years of age), divided into two groups by the dose of ICS (budesonide or equivalent): 800 and > 800 µg/day. At baseline, the forced expiratory volume in one second (FEV1) and the FEV1/forced vital capacity (FVC) ratio were both < 80% of the predicted values in 50.8% of the patients. The median age of the patients was 10.4 years (interquartile range 7.8–13.6 years). In the sample as a whole, there were significant increases in FEV1% and in the FEV1/FVC% ratio (p = 0.01 and p < 0.001, respectively) over the course of the study. In the > 800 µg/day group, there were no statistical increases or decreases in FEV1, the FEV1/FVC ratio, or forced expiratory flow between 25 and 75% of the FVC (FEF25–75%), when calculated as percentages of the predicted values. However, the z-score for FEF25–75% showed a statistically significant reduction, in the sample as a whole and in the > 800 µg/day group. Also in the > 800 µg/day group, there was a significant reduction in the post-bronchodilator FEV1% (p = 0.004). The fact that the spirometric parameters (as percentages of the predicted values) remained constant in the > 800 µg/day group, whereas there was a gain in lung function in the sample as a whole, suggests an early plateau phase in the > 800 µg/day group. However, there was some loss of lung function in the > 800 µg/day group, as evidenced by a decrease in the z-score for FEF25–75%, suggesting irreversible small airway impairment, and by a reduction in the post-bronchodilator FEV1%, suggesting reduced reversibility of airway obstruction. Among children and adolescents with severe asthma, the use of ICS doses higher than those recommended for age does not appear to improve lung function.