Obesity enhances eosinophilic inflammation in a murine model of allergic asthma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Is the prevalence of asthma and related symptoms among Brazilian children related to socioeconomic status?

Objective. To evaluate the relationship between socioeconomic status (SES) and the prevalence of asthma and related symptoms among Brazilian children. Methods. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire was applied to 23,457 six- to seven- year-old schoolchildren (SC) and 58,144 thirteen- to fourteen-year-old adolescents (AD) from 20 Brazilian cities. SES was evaluated by infant mortality index, poverty index, and average nominal income for people older than 10 years of age. Results. Current asthma ranged from 16.5% to 31.2% among SC and from 11.8% to 30.5% among AD and severe asthma from 2.9% to 8.5% (SC) and 2.6% to 9.1% (AD). Higher values were observed in Brazilian-Northern, -Northeastern and -Southeastern centers. No significant association between SES and prevalence of asthma and related symptoms was observed. Conclusions. In Brazil, the prevalence of asthma and related symptoms is quite variable and independent of SES. Copyright © 2008 Informa Healthcare USA, Inc.

Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 mu g b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmaceutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 mu g b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF).The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV1) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events.In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV1 and asthma control when compared to a combination of budesonide plus formoterol. (Clinical Trial number: ISRCTN60408425). (C) 2013 Elsevier Ltd. All rights reserved.

Prevalence of obesity and relationship wit body mass index and symptoms of asthma in adolescents

To investigate the relationship between Body Mass Index (BMI) and asthma symptoms in adolescents between 13 and 14 years, to estimate the prevalence of obesity in this age group. This is a crosssectional study with a quantitative approach which was rated the Body Mass Index (BMI) and applied the Questionnaire International Study of asthma and Allergies in Childhood (ISAAC) phase III (asthma module) to determine the prevalence of asthma and related symptoms, as well as its severity in 85teenagers. According to the assessment of asthma in relation to BMI, it was found that there were significant findings, as well as in males and females. However, the association between BMI and asthma symptoms, there was a significant association to present as disturbed sleep and impaired speech. Conclusions: In this sample the prevalence of obesity was low, this fact may have contributed to the nonsignificant findings betweenasthma and BMI.

Stem cell factor: a hemopoietic cytokine with important targets in asthma

We review evidence that Stem Cell Factor (SCF) plays an important role in the pathophysiology of asthma. SCF is produced by a wide variety of cells present in asthmatic lung, including mast cells and eosinophils. Its receptor, c-kit, is broadly expressed on mature mast cells and eosinophils. SCF promotes recruitment of mast cell progenitors into tissues, as well as their local maturation and activation. It also promotes eosinophil survival, maturation and functional activation. SCF enhances IgE-dependent release of mediators from mast cells, including histamine, leukotrienes, cytokines (TNF-alpha, IL-5, GM-CSF) and chemokines (RANTES/CCL5, MCP-1/CCL2, TARC/CCL17 e MDC/CCL22); it is required for IL-4 production in mast cells. SCF, acting in concert with IgE, also upregulates the expression and function of CC chemokine receptors in mast cells. Structural and resident airway cells express increased levels of SCF in the bronchus of asthmatic patients. In a murine model of asthma, allergen exposure increased production of SCF by epithelial cells and alveolar macrophages, which was transient and paralleled by histamine release. SCF induced long-lived airway hyperreactivity, which was prevented by local neutralization of SCF, as well as by inhibitors of the production or activity of cysteinyl-leukotrienes. Together, these observations suggest that SCF has an important role in asthma.

Behavior problems and prevalence of asthma symptoms among Brazilian children

Objective: Asthma is the most common chronic disease in childhood and has been designated a public health problem due to the increase in its prevalence in recent decades, the amount of health service expenditure it absorbs and an absence of consensus about its etiology. The relationships among psychosocial factors and the occurrence, symptomatology, and severity of asthma have recently been considered. There is still controversy about the association between asthma and a child`s mental health, since the pathways through which this relationship is established are complex and not well researched. This study aims to investigate whether behavior problems are associated with the prevalence of asthma symptoms in a large urban center in Latin America. Methods: It is a cross-section study of 869 children between 6 and 12 years old, residents of Salvador, Brazil. The International Study of Allergy and Asthma in Childhood (ISAAC) instrument was used to evaluate prevalence of asthma symptoms. The Child Behavior Checklist (CBCL) was employed to evaluate behavioral problems. Results: 19.26% (n = 212) of the children presented symptoms of asthma. 35% were classified as having clinical behavioral problems. Poisson`s robust regression model demonstrated a statistically significant association between the presence of behavioral problems and asthma symptoms occurrence (PR: 1.43; 95% Cl: 1.10-1.85). Conclusion: These results suggest an association between behavioral problems and pediatric asthma, and support the inclusion of mental health care in the provision of services for asthma morbidity. (C) 2011 Elsevier Inc. All rights reserved.

Prevalence of asthma and risk factors associated: population based study in Sao Paulo, Southeastern Brazil, 2008-2009

OBJECTIVE: To assess the prevalence of asthma and risk factors associated in children and adolescents. METHODS: Population-based cross-sectional study with 1,185 female and male children and adolescents carried out in the city of Sao Paulo, Southeastern Brazil, from 2008 to 2009. Data were collected through home interviews. Respondents were selected from two-stage (census tract, household) cluster random sampling stratified by gender and age. Multiple Poisson regression was used in the adjusted analysis between the outcome and socioeconomic, demographic, lifestyle and health condition variables. RESULTS: Of all respondents, 9.1% (95%CI 7.0; 11.7) reported asthma. After adjustment, the following variables were found independently associated with asthma: age (0 to 4 years vs. 15 to 19) (PR 3.18, 95%CI 1.20;8.42); age (5 to 9 years vs. 15 to 19) (PR 6.37, 95%CI 2.64;15.39); age (10 to 14 years vs. 15 to 19) (PR 4.51,95%CI 1.95;10.40); allergy (yes vs. no) (PR 2.22, 95%CI 1.24;4.00); rhinitis (yes vs. no) (PR 2.13, 95%CI 1.22;3.73); health conditions in the 15 days preceding the interview (yes vs. no) (PR 1.96, 95%CI 1.23;3.11); number of rooms in the household (1 to 3 vs. 4 and more) (PR 1.67, 95%CI 1.05;2.66); and skin color (black and mixed vs. white) (PR 2.00, 95%CI 1.14;3.49). CONCLUSIONS: This study showed the importance of factors associated with asthma including rhinitis and allergy; age between 5 to 9 years old; black and mixed skin color; and household with few rooms. Frequent health problems are seen as a common consequence of asthma.

Urban Air Pollutants are Significant Risk Factors for Asthma and Pneumonia in Children: The Influence of Location on the Measurement of Pollutants

Background: Air pollution is associated with a substantial burden on human health; however, the most important pollutants may vary with location. Proper monitoring is necessary to determine the effect of these pollutants on respiratory health. Objectives: This study was designed to evaluate the role of outdoor, indoor and personal exposure to combustion-related pollutants NO2 and O-3 on respiratory health of children in a non-affluent urban area of Sao Paulo, Brazil. Methods: Levels of NO2 and O-3 were continuously measured in outdoor and indoor air, as well as personal exposure, for 30 days using passive measurement monitors. Respiratory health was assessed with a Brazilian version of the ISAAC questionnaire. Results: Complete data were available from 64 children, aged 6-10 years. Respiratory morbidity was high, with 43 (67.2%) reporting having had wheezing at any time, 27 (42.2%) wheezing in the last month, 17 (26.6%) asthma at any time and 21(32.8%) pneumonia at any time. Correlations between levels of NO2 and O-3 measured in the three locations evaluated were poor. Levels of NO2 in indoor air and personal exposure to O-3 were independently associated with asthma (both cases P=.02), pneumonia (O-3, P=.02) and wheezing at any time (both cases P<.01). No associations were seen between outdoor NO2 and O-3 and respiratory health. Conclusions: Exposure to higher levels of NO2 and O-3 was associated with increased risk for asthma and pneumonia in children. Nonetheless, the place where the pollutants are measured influences the results. The measurements taken in indoor and personal exposure were the most accurate. (C) 2012 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety

OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients.

Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma

Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell's energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and disease. Using a mouse model of allergic airway inflammation disease and applying confocal microscopy, subcellular fractionation, and Western blot analysis we showed mitochondrial localization of GR alpha and ER beta in lung tissue. Allergic airway inflammation caused reduction in mtGR alpha, mtER beta, and OXPHOS enzyme biosynthesis in lung cells mitochondria and particularly in bronchial epithelial cells mitochondria, which was accompanied by decrease in lung mitochondrial mass and induction of apoptosis. Confirmation and validation of the reduction of the mitochondrial receptors in lung epithelial cells in human asthma was achieved by analyzing autopsies from fatal asthma cases. The presence of the mitochondrial GR alpha and ER beta in lung tissue cells and especially their reduction in bronchial epithelial cells during allergic airway inflammation suggests a crucial role of these receptors in the regulation of mitochondrial function in asthma, implicating their involvement in the pathophysiology of the disease.

Influence of asthma definition on the asthma-obesity relationship

Background: Epidemiological studies suggest an association between obesity and asthma in adults and children. Asthma diagnosis criteria are different among studies. The aim of this study was to test the influence of asthma definition on the asthma-obesity relationship. Methods: In a cross-sectional analysis of 1922 men and women, subjects completed a translated questionnaire from the European Community Respiratory Health Survey and underwent spirometry and a bronchial challenge test. Weight, height and waist circumference were measured. Multiple logistic regression analysis was carried out to assess the association of variables related to obesity and asthma. Asthma was defined either by the presence of symptoms with bronchial hyperresponsiveness (BHR) or by a self-report of a physician-made diagnosis. The following variables were separately tested for associations with asthma: socioeconomic characteristics, schooling, physical activity, smoking status, anthropometry and spirometry. Results: No association was detected between asthma confirmed by BHR and obesity indicators, odds ratio (OR) = 1.08 (95% confidence interval: 0.69 - 1.68) for obesity assessed by body mass index >= 30 kg/m(2); OR = 1.02 (0.74 - 1.40) for obesity assessed by abnormal waist-to-height ratio; and, OR = 0.96 (0.69 - 1.33) for abnormal waist circumference. On the contrary, a previous diagnosis of asthma was associated with obesity, OR = 1.48 (1.01 - 2.16) for body mass index >= 30 kg/m(2); OR = 1.48 (1.13 - 1.93) for abnormal waist-to-height ratio; and, OR = 1.32 (1.00 - 1.75) for abnormal waist circumference. Female gender, schooling >= 12 years and smoking were associated with BHR-confirmed asthma. Physically inactive subjects were associated with a previous diagnosis of asthma. Conclusions: Our findings indicate that the relationship between asthma and obesity in epidemiological studies depends on the definition adopted. Certain components of asthma, for instance, symptoms may be more prone to the obesity influence than other ones, like bronchial hyperresponsiveness.

Computerized cardiotocography in pregnancies complicated by maternal asthma

Objective: The aim of the present study was to investigate the FHR parameters in term pregnancies complicated by asthma. Study design: prospective cross-sectional study performed between July 2008 and November 2009. Twenty-one singleton pregnancy between 36 and 40 weeks gestation with diagnosis of maternal asthma and no current use of oral corticosteroids were compared with 30 pregnancies without morbidities at the same gestational age. The computerized cardiotocography (System 8002, Sonicaid) was performed and 30 min analysis was studied. Statistical analysis included Student's t-test or Mann-Whitney U test for comparisons between groups. Categorical data were compared using the chi(2)-test or Fisher's exact test. Results: There were no significant differences in FHR parameters analyzed by computerized cardiotocography: basal FHR (p = 0.80), number of accelerations >10 bpm (p = 0.08) or >15 bpm (p = 0.20), duration of high episodes (p = 0.70), duration of low episodes (p = 0.46) and STV (p = 0.66). Asthmatic mothers presented mean number of fetal movement per hour significantly lower than control group (34.6 +/- 28.2 vs. 60.6 +/- 43.1, p = 0.02). Conclusion: Computerized cardiotocography demonstrates no association between the abnormal parameters of FHR and maternal asthma in term pregnancies. Maternal asthma was associated with less fetal movements per hour, suggesting further studies on the counting of fetal movements in pregnant women with asthma.

Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

Background: Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo. Methods: Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (Delta R-rs) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient. Results: Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and DRrs, respectively (r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV1 reversibility (r = -0.65, P = 0.01; r = -0.54, P = 0.04). Conclusion: In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.

Temporal Trends of Asthma Mortality Rates in Brazil from 1980 to 2010

Objective. Mortality from asthma has varied among countries during the last several decades. This study aimed to identify temporal trends of asthma mortality in Brazil from 1980 to 2010. Method. We analyzed 6840 deaths of patients aged 5-34 years that occurred in Brazil with the underlying cause of asthma. We applied a log-linear model using Poisson regression to verify peaks and trends. We also calculated the point estimation and 95% confidence interval (CI 95%) of the annual percent change (APC) of the mortality rates, and the average annual percent change (AAPC) for 2001-2010. Results. A decline was observed from 1980 to 1992 [APC = -3.4 (-5.0 to -1.8)], followed by a nonsignificant rise until 1996 [APC = 6.8 (-1.4 to 15.6)], and a new downward trend from 1997 to 2010 [APC = -2.7 (-3.9 to -1.6)]. The APCs varied according to age strata: 5-14 years from 1980 to 2010 [-0.3 (-1.1 to 0.5)]; 15-24 years from 1980 to 1991 [-2.1 (-5.0 to 0.9)], from 1992 to 1996 [6.8 (-6.7 to 22.2)], and from 1997 to 2010 [-3.9 (-5.7 to -2.0)]; 24-25 years from 1980 to 1992 [-2.5 (-4.6 to -0.3)], from 1993 to 1995 [12.0 (-21.1 to 59.1)], and from 1996-2010 [-1.7 (-3.0 to -0.4)]. AAPC from 2001 to 2010 was -1.7 (-3.0 to -0.4); the decline for this period was significant for patients over 15 years old, women, and those living in the Southeast region. Conclusion. Asthma mortality rates in Brazil have been declining since the late 1990s.