Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum.

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.

Clinical, functional, and inflammatory characteristics of asthma among adults aged over 60 years old: a case-control study.

ObjectiveThis 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.MethodsPatients 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.ResultsPatients 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.ConclusionsThese 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.

Bronchodilator response as a hallmark of uncontrolled asthma: a randomised clinical trial.

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.

Anxiety and depression in asthma patients: impact on asthma control.

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.

Ansiedade e depressão em pacientes com asma: impacto no controle da asma / Anxiety and depression in asthma patients: impact on asthma control

OBJETIVO: Existem evidências da associação entre asma e sintomas psiquiátricos e transtornos mentais. Essa associação pode resultar em dificuldades de se atingir o controle da asma. O objetivo deste estudo foi avaliar a associação de ansiedade e depressão com o controle da asma. MÉTODOS: Estudo transversal com 78 pacientes asmáticos com diagnóstico confirmado de asma moderada a grave e regularmente tratados no Ambulatório de Asma do Hospital São Paulo da Universidade Federal de São Paulo, São Paulo (SP). Os pacientes foram divididos em dois grupos em relação ao status de controle de asma, determinado através do teste de controle da asma, e, posteriormente, comparados em termos de dados demográficos, clínicos e espirométricos, escore do questionário de qualidade de vida para asma e escore da escala hospitalar de ansiedade e depressão. RESULTADOS: A maioria era do sexo feminino. Dos 78 pacientes, 49 (63 por cento) foram classificados como tendo asma não controlada. A prevalência de ansiedade e do binômio ansiedade/depressão foi significantemente maior entre os pacientes não controlados do que nos controlados (78 por cento e 100 por cento; p = 0,04 e p = 0,02, respectivamente), enquanto nem prevalência de depressão, nem os dados espirométricos ou de qualidade de vida diferiram entre os grupos. CONCLUSÕES: Nesta amostra, os pacientes com asma não controlada apresentaram uma maior prevalência de sintomas de ansiedade que aqueles com asma controlada. Na avaliação de pacientes asmáticos, deve-se considerar o impacto negativo dos distúrbios de humor nas estratégias de controle da asma.

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 percent) 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 percent and 100 percent; 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.

Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma.

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.

Desempenho de uma escala analógica visual legendada na determinação do grau de dispneia durante teste de broncoespasmo induzido por exercício em crianças e adolescentes asmáticos / Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma

OBJETIVO: Existe uma relação indireta entre a obstrução das vias aéreas em asma e a intensidade de falta de ar (dispneia). Uma escala visual analógica legendada de dispneia com escore de 0-3 pontos tem sido amplamente utilizada na avaliação da broncoconstrição, embora a percepção de tal obstrução seja muito variável. O objetivo deste estudo foi determinar se crianças e adolescentes são capazes de perceber a broncoconstrição aguda induzida por exercício (BAIE), bem como medir o poder discriminatório de uma escala visual analógica legendada de dispneia em relação à intensidade de BAIE. MÉTODOS: Estudo transversal com 134 crianças e adolescentes asmáticos que foram submetidos a um teste de broncoespasmo induzido por seis minutos de exercício em um cicloergômetro. A intensidade da dispneia foi determinada utilizando-se uma escala visual analógica legendada de dispneia antes de cada determinação de VEF1. A escala tem um escore de 0-3 pontos, com desenhos em uma sequência lógica variando entre "sem sintomas" e "dispneia grave". As variáveis foram determinadas no momento basal, assim como em 5, 10 e 20 minutos após o término do teste de exercício. A acurácia da escala de dispneia em detectar o grau de BAIE foi determinada através de curvas ROC para a queda de VEF1 após o exercício, usando pontos de corte de 10 por cento, 20 por cento, 30 por cento e 40 por cento. RESULTADOS: Dos pacientes selecionados, 111 completaram o estudo, e 52 (46,8 por cento) apresentaram BAIE. A área sob a curva ROC progressivamente aumentou com o aumento do grau de broncoconstrição. CONCLUSÕES: Em crianças e adolescentes asmáticos, a acurácia desta escala de dispneia melhora com o aumento do percentual de queda em VEF1 após o exercício. Entretanto, o valor preditivo da escala é subótimo quando a porcentagem de queda em VEF1é menor.

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 percent, 20 percent, 30 percent, and 40 percent. RESULTS: Of the patients selected, 111 finished the study, and 52 (46.8 percent) 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.

Time required to achieve asthma control in not previously inhaled corticosteroid treated adult patients.

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.

Clinical markers of asthma severity: a family study

The purpose was to study the distribution of clinical expression of asthma in asthmatic families regarding age at asthma onset, duration of disease, skin prick test, serum total IgE, FEV1, therapeutic management and inheritance to find markers of severity of the disease. Sixty-eight subjects from 11 families were selected; 28 asthmatic patients were eligible to participate in the study, since they belonged at least to two family generations. Forty nonasthmatic relatives were also included. The asthmatics were submitted to a clinical questionnaire, physical examination, pre- and postbronchodilator spirometry, bronchial hiperesponsiveness test to histamine, skin prick test, and total serum IgE analysis. Asthma severity classification was: 11 mild (39 percent), 8 moderate (29 percent), and 9 severe (32 percent). Only two of seven markers of the disease were associated with asthma severity (p<0.05). Asthma severity was significantly associated with correct or incorrect treatment (p=0.004). The patients who correctly followed treatment had less severe disease than those patients who followed it incorrectly. Also, asthma severity was significantly associated with the degree of obstruction measured by FEVi (p=0.02). There is no significant association with the other tested markers. We conclude that asthma severity was highly related to poor or no effective treatment, such as no regular anti-inflammatory medication intake, frequent exposure to common indoor and outdoor triggers and difficuity in recognizing early warning signs as well as the degree of obstruction.