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Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients' sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.

Objective This observational case-control study analyzed the clinical, functional, inflammatory profile, and treatment data of a cohort of patients with asthma who were followed up at the outpatient clinic of a teaching hospital. Methods Patients who visited the clinic between January 2008 and February 2020 and diagnosed with asthma according to the Global Initiative for Asthma (GINA) criteria were included in the study. Patients were broadly classified into two groups: age <60 or age ≥60 years. The patients were evaluated for asthma control and severity, medications used, comorbidities, smoking status, occurrence of exacerbation, spirometry at the first and last visits, sputum cytology, allergic prick test, and inflammatory cytokine levels. Results Patients over 60 years of age had lower asthma control test (ACT) scores, required higher doses of inhaled corticosteroids to achieve asthma control and had worse lung function with fixed airway obstruction, higher number of comorbidities, greater exposure to tobacco, and longer outpatient follow-up than younger patients with asthma. Furthermore, older patients presented with neutrophilia and higher levels of TNFα in the induced sputum as compared to younger patients. Conclusions These findings suggest that patients aged ≥60 years of age had a more severe asthma profile and poorer lung function than younger patients with asthma. Furthermore, aging, long-term asthma, comorbidities, and tobacco exposure contributed to an accelerated decline in lung function.

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.

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.

Background and Objective: Determination of asthma phenotypes, particularly inflammatory phenotypes, helps guide treatment and management of this heterogeneous disease. Induced sputum cytology has been the gold standard for determination of inflammatory phenotypes, but sputum induction is fairly invasive and technically challenging. Blood and nasal lavage cytology have been suggested as substitutes, but have not been fully verified. The aim of this study is to determine the accuracy of blood and nasal lavage cytometry as indicators of inflammatory phenotypes in asthma., Methods: Clinical evaluation, Asthma Control Questionnaire (ACQ) and spirometry were performed for 121 adult asthma patients, and blood, nasal lavage and induced sputum samples were taken. Eosinophils and neutrophils were counted in three samples from each subject. Inflammatory phenotypes (eosinophilic, neutrophilic, mixed and paucicellular) and cells counts were analysed using Venn diagram and receiver operating characteristic (ROC) curve, respectively., Results: ACQ score, spirometry and bronchodilator response did not differ among subjects with different inflammatory phenotypes. Inflammatory phenotypes defined by nasal lavage cytometry were in better concordance than those defined by blood cell counts with phenotypes determined by sputum cytology, and were significantly correlated with sputum phenotypes. For eosinophilia, nasal lavage cytology showed better accuracy than blood cytology (area under the curve (AUC): 0.89 vs 0.65). For all phenotypes, sensitivity and positive and negative predictive power were higher for nasal lavage cytometry than for blood. Blood cell counts gave a high level of false positives for all inflammatory phenotypes., Conclusion: We recommend nasal lavage cytology over blood cell count as a substitute for sputum cytology to identify inflammatory phenotypes in asthma., (© 2016 Asian Pacific Society of Respirology.)

Introduction: The goal of this study is to determine whether bronchodilator (BD) response can be used as a reliable measure of asthma control by analyzing the effects of a short course of oral corticosteroids (OC) or placebo (P) on spirometry, sputum cytology and BD response in controlled asthma patients scoring less than 1.5 on the ACQ5., Methods: Seventy patients with moderate to severe asthma who were undergoing combination therapy and were considered to be controlled based on ACQ5 scores, but who exhibited persistent positive BD response, were randomly assigned to two groups, one receiving OC and the other P. Patients were evaluated before and after 2 weeks of treatment. Intervention response (comparison of FEV(1) before and after OC or P treatment) was used as a measure of intervention efficacy, with values equal to or greater than 200 mL considered positive., Results: Patients who received OC showed significant improvement in FEV(1), and no longer exhibited a positive BD response. Those in the P group showed no change. In addition, sputum eosinophil counts significantly decreased in the OC group., Conclusions: BD response can be used as a reliable measure of asthma control. This study suggests that ACQ5 scores alone are not sufficient to fully assess asthma control, and that BD response should be included as an essential measurement in any algorithm of asthma control evaluation.

Objective: There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression., Methods: A crosssectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression., Results: The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score., Conclusions: In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.

Objective: There is an indirect relationship between airway obstruction in asthma and the intensity of breathlessness (dyspnea). A word labeled visual analog dyspnea scale with a 0-3 score has been widely used for the assessment of the degree of bronchoconstriction, although the perception of such obstruction varies considerably. The objective of this study was to determine whether children and adolescents are able to perceive acute exercise-induced bronchoconstriction (EIB), as well as to measure the discriminatory power of a word labeled visual analog dyspnea scale in relation to the intensity of the EIB., Methods: A cross-sectional study involving 134 children and adolescents with asthma and submitted to a six-minute steady-state exercise test on a cycle ergometer. The intensity of dyspnea was determined using a word labeled visual analog dyspnea scale prior to each determination of FEV1. The scale is scored from 0 to 3, with a logical sequence of pictures, ranging from "no symptoms" to "severe dyspnea". Variables were determined at baseline, as well as at 5, 10, and 20 min after the exercise test. The accuracy of the dyspnea scale in identifying the degree of EIB was determined by means of ROC curves for the post-exercise fall in FEV1, using cut-off points of 10%, 20%, 30%, and 40%., Results: Of the patients selected, 111 finished the study, and 52 (46.8%) presented with EIB. The area under the ROC curve increased in direct proportion to increases in the degree of bronchoconstriction., Conclusions: Among children and adolescents with asthma, the accuracy of this dyspnea scale improves as the post-exercise percentage fall in FEV1 increases. However, the predictive value of the scale is suboptimal when the percentage fall in FEV1 is lower.

Background: To achieve the best health possible, asthma patients require targeted education to understand the disease and how it may affect them, and what they need to do to keep it controlled., Aim: To measure the length of time needed in a structured educational training program to achieve well-controlled asthma status., Methods: This 5-month clinical trial enrolled previously untreated adult asthma patients at the Asthma Center of the President Dutra Public Hospital/Federal University of Maranhao-Brazil. At the first visit, patients were stratified according to their pre-bronchodilator peak expiratory flow rate (PEFR) measurements: Class I was defined as PEFR > 80% of the predicted value; Class II as PEFR 50-80% of predicted value, and Class III as PEFR < 50% of predicted value. At enrollment and each follow-up visit patients were assessed for asthma symptoms and health care utilization. In the educational program, sessions covered signs and symptoms of asthma exacerbation, triggering factors, environmental control, and asthma drug effects. The time required to achieve well-controlled status and the total time free of asthma symptoms were evaluated by Kaplan-Meier curves. The log-rank test was used to compare PEFR classes, with significance being measured as p-values < or = 0.05., Results: A total of 121 patients met the eligibility criteria and underwent the 6-month follow-up. The first six-month Kaplan-Meier curve demonstrated that Class I patients had a significantly better probability of achieving well-controlled asthma than the other classes (log rang = 6.78, p = 0.03), The second 6-month Kaplan-Meier curve analyzed the total time free of asthma symptoms according to PEFR class (log rank = 11, 22 p = 0.003). The time required to reach a well-controlled status was 2 or 3 months, depending on the baseline level of airway obstruction: patients in PEFR classes I and II achieved good control earlier than patients in PEFR Class III. Education and targeted training remain a key element of doctor-patient interactions and success of asthma control efforts.

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