Relations between asthma and obesity: an analysis of multiple factors / Relações entre asma e obesidade: análise de múltiplos fatores

ABSTRACT Objective: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. Methods: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. Results: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. Conclusions: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

RESUMO Objetivo: A asma e a obesidade são doenças prevalentes e inter-relacionadas. Na população pediátrica, o efeito da inflamação sistêmica associada à obesidade, levando à inflamação das vias aéreas, é controverso. Nosso objetivo foi comparar padrões inflamatórios, clínicos e espirométricos entre crianças obesas e aquelas com peso normal. Métodos: Setenta e nove meninos e meninas de 6‒10 anos de idade foram selecionados e divididos em quatro grupos: asmáticos obesos, asmáticos não obesos, não asmáticos obesos e não asmáticos não obesos. Além de dados clínicos e antropométricos, todas as crianças foram submetidas a espirometria e testes cutâneos para alérgenos inalantes. Também foram coletadas amostras de sangue para dosagem de citocinas e adipocinas. Resultados: Obesos asmáticos tiveram um controle significativamente pior da asma do que os não obesos (RP 4,9; IC95% 1,1‒22,1), independentemente do sexo, atividade física e atopia. Não foram observadas diferenças nos níveis de espirometria, citocinas Th1 e Th2 e adipocinas entre os quatro grupos. Os testes cutâneos foram positivos em 81,8 e 80% dos não obesos asmáticos e obesos asmáticos, respectivamente. Conclusões: O grau de controle da asma foi significativamente menor no grupo obeso, apesar de não ter havido diferenças nos achados espirométricos. Esse resultado sugere que fatores extrapulmonares podem ser responsáveis por esse perfil sintomático. A alta positividade do teste cutâneo nos dois grupos, considerado um bom marcador de atopia, demonstrou o componente atópico como preponderante na gênese da asma, tanto em crianças com obesidade quanto naquelas com peso normal.

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Hiperlactatemia en pacientes hospitalizados por asma: Frecuencia e implicaciones clínicas / Hyperlactatemia in hospitalized patients with asthma. Frequency and clinical implications

Se ha descrito un incremento del lactato sanguíneo en algunos pacientes tratados por agudización del asma. Sin embargo, se desconoce su frecuencia y el significado clínico en la práctica clínica habitual. El objetivo del estudio ha sido evaluar las características asociadas a la presencia de hiperlactatemia en la gasometría arterial de pacientes que requirieron ingreso en la sala de neumonología por agudización del asma. Se realizó un estudio retrospectivo de las altas hospitalarias de un servicio de neumonología durante 3 años (2015 a 2017) analizando los valores del ácido láctico en la gasometría arterial y su posible relación con datos de antecedentes clínicos, de laboratorio, tratamiento, espirometría, estancia hospitalaria o uso de unidades de cuidados críticos. Se incluyeron 112 pacientes con 182 ingresos. Presentaron en alguna ocasión hiperlactatemia (> 2.2 mmol/l) 32 pacientes (29%). En 42 de los 182 ingresos (23%) se observó aumento de lactato, en quienes tenían mayor estancia hospitalaria (mediana 6 vs. 5 días, p = 0.013). En 8 de los 10 ingresos en unidades de cuidados críticos se observó hiperlactatemia, en general tras recibir el tratamiento broncodilatador. En las gasometrías con hiperlactatemia existía una correlación significativa entre lactato y bicarbonato (r = -0.417, p=0.003) y el exceso de base (r = -0.484, p < 0.001). La hiperlactatemia es relativamente frecuente en las gasometrías realizadas a los pacientes hospitalizados por asma (23% de los ingresos). Los ingresos con hiperlactatemia se asociaron a una internación más prolongada.

Increased levels of lactic acid have been described in patients treated for asthma exacerbation. However, the frequency and clinical significance of hyperlactatemia in real-world practice is unknown. The objective of the study was to evaluate the characteristics associated with hyperlactatemia in blood gas analysis of patients with asthma exacerbation hospitalized in a pulmonary department. This is a retrospective 3-year study (2015 to 2017) of patients discharged from the pulmonary department. The level of lactic acid in the blood gas test and the possible relationship with clinical, laboratory, therapy, spirometric values, hospitalization length and use of critical care resources were analyzed. A total of 112 patients with 182 admissions were included in the study. Thirty-two (29%) patients had hyperlactatemia in at least one blood gas analysis. Elevated lactic acid was observed in 42 of 182 admissions (23%), which had larger length hospital stay (median, 6 vs. 5 days, p = 0.013). Hyperlactatemia was present in 8 of 10 admissions in the critical care units, mainly after receiving bronchodilator therapy. There was a significant correlation between lactate level and bicarbonate level (r = -0.417, p = 0.003) and between lactate level and base excess (r = -0.484, p < 0.001) in cases with hiperlactatemia. Hyperlactatemia is a relatively frequent finding in blood gas analysis of patients hospitalized because of asthma (23% of admissions). These admissions with hiperlactatemia are associated with larger hospital length of stay.

Mutações do gene do receptor de vitamina d e níveis séricos de vitamina d em crianças com asma / Vitamin d receptor gene mutations and vitamin d serum levels in asthmatic children

RESUMO Objetivo: Verificar a relação dos polimorfismos do gene do receptor de vitamina D (RVD) com sinais clínicos e níveis de vitamina D (VD) em asmáticos. Métodos: Estudo transversal com 77 crianças de 7 a 14 anos de um ambulatório especializado, divididas em 3 grupos: asmáticos, em uso de corticoide inalatório (ICS) por mais de um ano; asmáticos sem necessidade de ICS; não asmáticos e não alérgicos (de acordo com o International Study of Asthma and Allergies in Childhood - ISAAC. Foram avaliados: espirometria, testes alérgicos, presença do polimorfismo CDX2 do promotor do RVD por reação em cadeia da polimerase (PCR) e genotipagem de polimorfismos dos éxons 2 e 3 por PCR-SSCA (single-strand conformational analysis), imunoglobulina E (IgE) total e IgE específica para ácaros e gramíneas nos três grupos estudados. Níveis de 25-hidroxivitamina D foram dosados nos asmáticos. Resultados: A média de idade foi 10,8±2,2 anos, 57% masculinos, 38 asmáticos com ICS, 22 sem ICS e 17 não asmáticos. Rinite alérgica esteve presente em 90% dos asmáticos, polimorfismo CDX2 em 23% dos asmáticos e ausente nos controles (p=0,03). Menores níveis de volume expiratório forçado no primeiro segundo (VEF1%) foram observados nos asmáticos homozigotos para CDX2 (p=0,001). Variações nas sequências dos éxons 2 e 3 não foram relacionadas com a asma ou demais testes. Deficiência ou insuficiência de VD foi diagnosticada em 98% dos asmáticos. Não houve associação entre níveis de VD e polimorfismos genéticos dos éxons 2 e 3. Conclusões: Observou-se associação positiva entre polimorfismo CDX2 em homozigoze com asma e menores valores de VEF1%. O CDX2 pode modificar a interação celular do RVD com a vitamina, bem como pode estar associado com a asma e com a dificuldade de controle da doença.

ABSTRACT Objective: To verify the relationship between polymorphisms of the vitamin D receptor gene (VDR), clinical findings, and serum vitamin D (VD) levels in asthmatics. Methods: A cross sectional study of 77 children aged 7 to 14 years old, who were attended at a specialized clinic. The children were divided into 3 groups: asthmatics who had been using inhaled corticosteroids (ICS) for more than one year; asthmatics who had not been using ICS; non-asthmatics, and children without allergies (according to the International Study of Asthma and Allergies in Childhood ­- ISAAC). Spirometry, skin prick tests, the presence of a VDR promoter CDX2 polymorphism from an allele-specific polimerase chain reaction (PCR), exons 2 and 3 polymorphisms genotyping by PCR-SSCA (single-strand conformational analysis), total immunoglobulin E (IgE) and specific IgE to mites and grass were evaluated in these three groups. Levels of 25-hydroxyvitamin D were determined in asthmatics only. Results: The mean age of the children was 10.8±2.0 years old, 57% were male, 38 were asthmatic and using ICS, 22 were asthmatic and not using ICS, and 17 were non-asthmatic. Allergic rhinitis was present in 90% of asthmatics. Homozygous CDX2 was detected in 23% of the patients and absent in the control group (p=0.03). Lower forced expiratory volume in 1 second (FEV1%) values were observed in CDX2 homozygous asthmatics (p=0.001). Variations in the exon 2 and 3 sequences were not related to asthma or the other tests. VD deficiency or insufficiency was detected in 98% of asthmatics. There was no association between VD levels and genetic polymorphisms from exons 2 and 3. Conclusions: There was a positive association between homozygous CDX2 polymorphism, asthma and lower FEV1% values. CDX2 is capable of modifying cell interaction between VDR and VD, and it could be associated with the prevalence of asthma, and the difficulty in controlling the disease.

Virus más frecuentemente aislados en la exacerbación de asma y su correlación con nivelesde eosinófilos e inmunoglobulina E sérica total / Most commonly isolated viruses in asthma exacerbation and their correlation with eosinophil and total serum immunoglobulin E levels

Antecedentes. Las exacerbaciones de asma continúan siendo una causa de hospitalización en el Servicio de Urgencias. Los desencadenantesson alérgenos e infecciones, principalmente, de tipo viral. El objetivo fue determinar la relación entre los virus detectados durante la exacerbación asmática y los niveles de eosinófilos e inmunoglobulina E (IgE) sérica en pacientes pediátricos. Población y métodos. Estudio transversal analítico. Se incluyeron niños de cinco a quince años atendidos en Urgencias de Pediatría con exacerbación de asma, en el período de marzo de 2013 a febrero de 2016. Se obtuvo ácido ribonucleico viral en el aspirado nasofaríngeo con el kit CLART PneumoVir. Se cuantificaron los eosinófilos en la sangre periférica y los niveles de IgE sérica total. Se consideró eosinofilia un conteo ≥ 0,4 x 103/mm3 e IgE elevada, ≥ 350 UI/L. Se realizó la correlación de Pearson. Se definió significancia con valor de p ≤ 0,05.Resultados. De 211 niños con exacerbación de asma, en el 20%, se aisló un virus. Los virus aislados más frecuentemente fueron el rinovirus, el enterovirus y el virus sincitial respiratorio. Se encontró una correlación entre los niveles de eosinófilos e IgE sérica total en los niños con exacerbación de asma y rinovirus de 0,89, con una p= 0,0001.Conclusiones. Las infecciones por rinovirus, enterovirus y virus sincitial respiratorio son más frecuentes en las exacerbaciones de asma en menores de 15 años. Se observó una correlación entre los niveles de eosinófilos e IgE en presencia de rinovirus.

Background. Asthma exacerbations are still a cause of hospitalization at the Emergency Department. The triggers of asthma exacerbations include allergens and infections ­mostly viral­. The objective of this study was to establish the relationship between viruses detected during an asthma exacerbation and eosinophil and serum immunoglobulin E (IgE) levels in pediatric patients. Population and methods. Cross-sectional. analytical study. Children aged 5-15 years seen at the Pediatric Emergency Department with an asthma exacerbation in the period between March 2013 and February 2016 were included. Viral ribonucleic acid was extracted from nasopharyngeal aspirates using the CLART Pneumo Vir kit. Eosinophil levels were measured in peripheral blood and total IgE levels, in serum. Eosinophilia was defined as a count ≥ 0.4 x 103/mm3 and high IgE. as a level ≥ 350 IU/L. The Pearson's correlation was carried out. A value of p ≤ 0.05 was considered significant.Results. Out of 211 children with asthma exacerbation, a virus was isolated in 20%. The most commonly isolated viruses were rhinovirus. enterovirus, and respiratory syncytial virus. A correlation of 0.89 was established between eosinophil and total serum IgE levels in children with asthma exacerbation and rhinovirus, with a p value of 0.0001. Conclusions. Rhinovirus, enterovirus, and respiratory syncytial virus were the most common viruses in asthma exacerbations in children younger than 15 years. A correlation was established between eosinophil and IgE levels in the presence of rhinovirus.

Obesity and asthma: clinical and laboratory characterization of a common combination / Obesidade e asma: caracterização clínica e laboratorial de uma associação frequente

ABSTRACT Objective: To evaluate the relationship between obesity and asthma. Methods: This was a preliminary cross-sectional analysis involving 925 subjects with mild-to-moderate or severe asthma evaluated between 2013 and 2015. Obesity was defined on the basis of body mass index (BMI) and abdominal circumference. We collected clinical, laboratory, and anthropometric parameters, as well as pulmonary function test results and data regarding comorbidities. The subjects also completed asthma control and quality of life questionnaires. Results: Obese individuals had a significantly higher number of neutrophils in peripheral blood than did nonobese individuals (p = 0.01). Among the obese individuals, 163 (61%) had positive skin-prick test results, as did 69% and 71% of the individuals classified as being overweight or normal weight, respectively. Obese individuals showed lower spirometric values than did nonobese individuals, and 32% of the obese individuals had uncontrolled asthma, a significantly higher proportion than that found in the other groups (p = 0.02). Conclusions: Obese individuals with asthma seem to present with poorer asthma control and lower pulmonary function values than do nonobese individuals. The proportion of subjects with nonatopic asthma was higher in the obese group. Our results suggest that obese individuals with asthma show a distinct inflammatory pattern and are more likely to present with difficult-to-control asthma than are nonobese individuals.

RESUMO Objetivo: Avaliar a relação entre obesidade e asma. Métodos: Análise preliminar transversal de dados de um estudo de caso-controle com 925 pacientes com asma leve a moderada ou grave, avaliados entre 2013 e 2015. A classificação de obesidade levou em conta o índice de massa corpórea (IMC) e a circunferência abdominal. Foram coletados parâmetros clínicos, laboratoriais, medidas antropométricas e de função pulmonar, assim como resultados de questionários de controle da asma e de qualidade de vida e presença de comorbidades. Resultados: Os indivíduos obesos apresentaram um número significativamente maior de neutrófilos no sangue periférico que os não obesos (p = 0,01). Entre os obesos, 163 (55%) apresentaram positividade no teste alérgico, enquanto os grupos com sobrepeso e IMC normal apresentaram positividade em 62% e 67%, respectivamente. Os parâmetros espirométricos dos indivíduos obesos foram mais baixos que os dos não obesos, e 97 obesos (32%) apresentaram asma não controlada, uma proporção significativamente maior do que a observada nos demais grupos de estudo (p = 0,02). Conclusões: Indivíduos asmáticos e obesos têm pior controle da asma e valores mais baixos de parâmetros de função pulmonar que os não obesos. A proporção de pacientes sem atopia entre asmáticos obesos foi maior que entre os não obesos. Nossos resultados sugerem que indivíduos asmáticos obesos podem apresentar um padrão inflamatório diferente do habitual e doença de mais difícil controle quando comparados com indivíduos asmáticos não obesos.

Efectos de la concentración de 25-hidroxi vitamina D sobre la gravedad y el control del asma en pacientes asmáticos en edad escolar / Effects of 25 hydroxy vitamin D levels on the severity and asthma control in school age asthma patients

Objetivo. Determinar la concentración de vitamina D en pacientes de entre 6 y 18 años de edad sometidos a un seguimiento por asma y la relación entre la concentración de vitamina D y el control y la gravedad del asma. Materiales y métodos. Se inscribió en el estudio a pacientes con asma y voluntarios sanos de entre 6 y 18 años de edad, asignados al grupo de pacientes y al grupo de referencia, respectivamente. Se registraron las características demográficas y los hallazgos clínicos de los pacientes, y se les realizó una prueba funcional respiratoria. Se estimaron el índice de masa corporal (IMC) y la concentración de 25-hidroxi vitamina D (25(OH)D), calcio, fósforo, fosfatasa alcalina, inmunoglobulina E total y eosinófilos de todos los pacientes. La gravedad del asma y las condiciones de control se determinaron según los criterios de la Iniciativa Global para el Asma (Global Initiative for Asthma, GINA). Resultados. Se incluyó a 72 pacientes con asma y a 66 niños sanos. En comparación con el grupo de referencia, en el grupo de pacientes se detectó una menor concentración de vitamina D. En 38 (52,8%) niños del grupo de pacientes con asma se observó deficiencia de vitamina D; en este grupo, el control del asma era deficiente y la gravedad, significativamente mayor. No se observó una correlación significativa entre la concentración de vitamina D y el sexo, la obesidad, las pruebas funcionales respiratorias, las pruebas cutáneas, la concentración sérica de eosinófilos e inmunoglobulina E (IgE) total. Conclusión. La deficiencia y la insuficiencia de vitamina D fueron más frecuentes en los niños con asma, en comparación con los niños del grupo de referencia. Una menor concentración de vitamina D se asocia con un control deficiente del asma y una mayor gravedad de esta.

Background. The objective was to determine vitamin D levels in patients between the ages 6 and 18 years, followed for asthma, and the relation between vitamin D levels and asthma control and severity. Materials and Methods. Patients with asthma and healthy volunteers between the ages 6 and 18 years were enrolled into the study as patient and control groups, respectively. Patient demographic information and clinical findings were recorded; a respiratory function test was performed. Body mass index (BMI), 25(OH) D,calcium, phosphorus, alkaline phosphatase, total IgE and eosinophil levels were determined for all patients. Asthma severity and control conditions were established based on GINA (Global Initiative for Asthma) criteria. Results. Seventy two patients with asthma and 66 healthy children were included. Compared to the control group, decreased serum vitamin D levels were detected in patient group. Thirty eight (52.8%) patients in asthma patient group had vitamin D defficiency; in this group, asthma control was poor and asthma severity was significantly higher. No significant correlation was found between vitamin D levels and gender, obesity, respiratory functions, skin test, serum eosinophil and total IgE levels. Conclusion. The frequency of vitamin D deficiency and insufficiency was higher in children with asthma, compared to the controls. Lower levels of vitamin D are associated with poor asthma control and increased asthma severity.

Expression of resistin, CXCR3, IP-10, CCR5 and MIP-1α in obese patients with different severity of asthma

Asthma studies suggest that alteration in the inflammation pattern may be associated with the severity of asthma. The aim of this study was to compare in vitro the expression of chemokines, chemokine receptors and cytokine production from CD4+ T human lymphocytes of asthmatic, both obese and non-obese patients with different severity levels of asthma. Lymphocytes were labeled with monoclonal anti-human CXCR3/IP-10, MIP-1a/CCR5 antibodies and were analyzed by flow cytometry. Cell culture supernatants were used to measure production of interleukin IL-6 and resistin by ELISA. CXCR3/IP-10 expression increased in non-obese patients with mild persistent asthma (2.2%, p<0.05), moderate persistent asthma (3%, p<0.003) and severe persistent asthma (4%, p<0.004); this effect was stronger in obese patients with severe persistent asthma (35%, p<0.004). MIP-1 α / CCR5 increased in non-obese patients with intermittent asthma (0.65%, p<0.05) and severe asthma (1.4%, p<0.03); in obese patients, this expression was greater in intermittent asthma (8%, p<0.05) and severe persistent asthma (12%, p<0.04). Resistin production strongly increased in obese patients with intermittent (976 ng/ml) and severe persistent asthma (795 ng/ml). IL-6 increased in both lean and obese persons; however, the highest value was registered in the group of severe persistent obese asthmatics (992 pg/ml). Obesity per se increased the inflammatory profile of chemokines / cytokines secreted by cells of the blood, increasing the inflammatory status in asthmatic patients. Resistin showed characteristics of a pro-inflammatory cytokine mainly in severely obese asthmatics.

Perfil de producción de citoquinas en linfocitos T de sangre periférica de pacientes con poliposis nasal y asma bronquial en respuesta a la estimulación con enterotoxina estafilocócica B / Cytokine production profile in peripheral blood T lymphocytes from patients with nasal poliposis and bronchial asthma in response to staphylococcal enterotoxin B

Introducción: La poliposis nasal (PN) se presenta frecuentemente asociada a asma bronquial (AB). La enterotoxina estafilocócica B (SEB) jugaría un papel en su patogenia. No se ha estudiado si el perfil de citoquinas inducido por SEB en linfocitos T (LT) de pacientes con PNyAB difiere del de controles sanos. Objetivo: Comparar el perfil de citoquinas de LT de sangre periférica de pacientes con PN-AByde controles, estimulados con SEB o concanavalina A (ConA). Material y método: Células mononucleares de sangre periférica de 9 pacientes con PN-AB y de 6 controles se estimularon con SEB o ConA. El porcentaje LT CD4+ productores de interferón (IFN)-y, interleuquina (IL) IL-4, IL-5, IL-17 e IL-21 se determinó mediante citometrfa de flujo. Resultados: El grupo PN-AB presentó un menor porcentaje de LT productores de IL-5 que los controles al estimularse con SEB y con ConA. No hubo diferencia en las otras citoquinas estudiadas. Discusión: Nuestros resultados en sangre periférica difieren de lo descrito en tejido de pólipos nasales. Conclusión: Se sugiere que la respuesta inflamatoria de la PN se originaría localmente ya que los LT de sangre de pacientes con PN-AB no muestran una polarización hacia perfiles proinflamatorios con los estímulos utilizados.

Introduction: Nasal poliposis (NP) is frequently associated with bronchial asthma (BA) and its pathogenesis is still unknown. Staphylococcal enterotoxin B (SEB) has been implicated in the development of NP, however if the SEB-induced cytoklne profile of peripheral blood T lymphocytes (TL) of PN-BA patients differs from that of normal controls has not been studied. Aim: To compare the cytoklne profile of CD4+ TL from NP-BA and controls stimulated with SEB or concanavalin A (ConA). Material and method: Peripheral blood mononuclear cells from 9 NP-BA patients and from 6 controls were stimulated with SEB or ConA. The percentage of interferon (IFN)-y, interleukin {II) 11-4,11-5,11-17, and 11-21 producing TL was analyzed by flow cytometry Results: The percentage of SEB and ConA stimulated CD4+ IL-5-producing TLs was lower in the NP-BA group compared to the control group. There were no differences in the other cytokine-producing populations. Discussion: Unlike what is described in nasal polyp tissue, our findings show a diminished production of IL-5 by peripheral TL from the NP-AB group. Conclusion: A local sinonasal origin of the chronic inflammation is suggested since peripheral blood TL of NP-BA patients do not show a pro-inflammatory polarization with the tested stimuli.

Investigating the effect of the homeopathic immunomodulator, MODUL8® on Blood count, bronchial lavage and fibrin ultrastructure on experimental asthmatic BALB/c mice / Investigación del efecto del inmunomodulador homeopatico Modul8® sobre sangre, lavado bronquial y ultraestructura de la fibrina en ratones experimentales asmáticos BALB/c

Modul8® is a composite mixture of natural products that are known to be an immunomodulator. In the current study the effect of this immunomodulator is tested on an experimental asthmatic BALB/c mouse model to investigate its properties on the white blood cell count in the blood and bronchial lavage of the animals since white blood cells play a fundamental role in the inflammatory process involved in asthma. As it is known that platelets also play an important role in the immune system, the ultrastructure of platelets and fibrin networks were also investigated by scanning electron microscopy. The animals were sensitised, nebulized and treated over a period of 43 days until termination. Results from the blood smears as well as the bronchial lavage smears revealed significantly higher eosinophil counts in the asthmatic group compared to the control and treated groups. Changes in the ultrastructure of the platelets and fibrin networks could also be observed, with the Modul8® -treated group appearing similar to that of the control group where thick major and thin minor fibres could clearly be distinguished and a tight mass of platelet aggregate could be observed. Whereas the fibrin networks from the asthmatic animals appeared flimsy with a tight mass of thin fibres covering the thick major fibres. The asthmatic platelet aggregates appeared granular without the tight round appearance of the control platelet aggregates. It is therefore concluded that Modul8® positively influences the white blood cell counts by altering the asthmatic profile to look similar to that of the control. Also, it seems as if Modul8® has a stabilizing effect on the platelets and fibrin networks. From these results it can be suggested that Modul8® might successfully be used in the treatment of inflammatory conditions such as asthma.

Modul8® es una mezcla compuesta de productos naturales que es conocida por ser un inmunomodulador. En el presente estudio, el efecto de este inmunomodulador se prueba de forma experimental en el modelo de ratón asmáticos BALB/c, para investigar sus propiedades sobre el conteo de glóbulos blancos en la sangre y lavado bronquial de los animales, ya que los glóbulos blancos desempeñan un papel fundamental en el proceso de respuesta inflamatoria implicado en el asma. Como es sabido, también las plaquetas desempeñan un papel importante en el sistema inmunológico, así, la ultraestructura de las plaquetas y las redes de fibrina también fueron investigadas por microscopía electrónica de barrido. Los animales fueron sensibilizados, nebulizados y tratados durante un período de 43 días hasta el término. Los resultados de los frotis de sangre, así como los de lavado bronquial revelaron un número significativamente mayor de eosinófilos en el grupo de asmáticos en comparación con el control y grupos tratados. Cambios en la ultraestructura de las plaquetas y redes de fibrina también pueden ser observados, donde el grupo tratado con la Modul8® aparece similar a el grupo control, donde los fibras de mayor grosor y menor grosor pueden ser claramente distinguidas y además, puede ser observada una apretada masa de plaquetas aglutinadas. Considerando las redes de la fibrina en animales asmáticos parecen endebles con una apretada masa de fibras de menor grosor que cubren las fibras de mayor grosor. Los agregados de plaquetas en asmáticos aparecen granulares sin el aspecto apretado del agregado plaquetario que rodea al grupo control. Por tanto, se concluye que Modul8® positivamente influye en el conteo de glóbulos blancos mediante la alteración del perfil de asmáticos a un aspecto similar al del control. Además, parece como si Modul8® tuviera un efecto estabilizador en las plaquetas y las redes de fibrina. De estos resultados se puede sugerir que Modul8® puede ser utilizado...

Assessment of inflammation based on the release of oxygen radicals by granulocytes in chronic uncontrolled asthma / Avaliação da inflamação com base na liberação de radicais oxidantes por granulócitos na asma crônica não-controlada

Objetivo: Avaliar a liberação espontânea de ânion superóxidopor granulócitos de sangue periférico de pacientescomasma crônica não-controlada antes e após corticoterapia e de indivíduos sadios. Métodos: Foram estudados 32 pacientes entre 6 e 18 anos (média 12,04 anos) e 29 indivíduos sadios como grupo decomparação.Os pacientes oramagrupados de acordocomo volumeexpiratório forçado no primeiro segundo: grupo I, volume expiratórioforçado no primeiro segundo entre 60 e 80%, 19 pacientes; e grupo II, volume expiratório forçado no primeiro segundo = 60%, 13 pacientes. A liberação espontânea de superóxido por granulócitos, medida por espectrofotometria utilizando superóxido dismutase, foi avaliada nos pacientes antes e após o tratamento com prednisona por via oral e beclometasona, budesonida ou fluticasona administradas por via inalatória. Na análise estatística foramutilizados os testes de análise de variância, Tukey e de Wilcoxon.Resultados: Comparando-se a liberação de ânion superóxido por granulócitos dos pacientes asmáticos e indivíduos sadios observamosque a liberação foi maior nos asmáticos não-controladosdo grupo II (p < 0,05). Avaliando-se a liberação de superóxido pelas células dos pacientes antes e após a terapiacomcorticosteroideuma diminuição significativa foi observada apenas no grupo I. Conclusão: O impacto dos glicocorticoides sobre a modulação da inflamação ocorreu nos indivíduos asmáticos não-controlados com volume expiratório forçado no primeiro segundo entre 60 e 80%.Naqueles com volume expiratório forçado no primeiro segundo = 60não foi observada essa modulação, havendo necessidade de mais estudos para avaliar o impacto de tal achado nos pacientes asmáticos.

Objective: To evaluate spontaneous release of superoxide anion by peripheral blood granulocytes of atopic patients with uncontrolled asthma undergoing glucocorticoid therapy and of healthy subjects. Methods: We studied 32 patients, aged 6 to 18 (mean 12.04), and 29 healthy subjects as a comparative group. Patients weregrouped according to the forced expiratory vital capacity in the firstsecond. Group I, forced expiratory vital capacity in the first second of between60and80%,had 19 patients, and group II, forced expiratoryvital capacity in the first second=60%,had 13 patients. Spontaneous superoxide release by granulocytes was measured by aspectrophotometer method based on superoxide dismutase, before and after oral prednisone and beclomethasone, budesonide or fluticasone inhaled therapy. Statistical analyses were performed using ANOVA, Wilcoxon and Tukey tests. Results: Comparing the superoxide anion release bygranulocytes of asthmatic patients and healthy subjects,weobserved a higher release by cells of the uncontrolled patient group II (p < 0.05). Evaluating the superoxide release by cells of asthmatic patients before and after steroid therapy, a significant decrease was found only in patient group I.Conclusion: The impact of corticosteroids on inflammatorymodulation occurred in the uncontrolled asthmatics with forced expiratory vital capacity in the first second between 60 and 80%. In those with forced expiratory vital capacity in the first second of = 60%, this findingwas not observed. Further studies are necessary to evaluate the effect of this finding on asthmatic patients.

Cortisol basal em asmáticos em uso de duas diferentes doses de propionato de fluticasona / Basal cortisol in asthmatics on two different doses of fluticasone propionate

OBJETIVOS: Avaliar os valores de cortisol basal em asmáticos persistentes em uso de propionato de fluticasona inalatório na dose de 200 ou 300 mcg/dia. MÉTODOS: O diagnóstico e a classificação da gravidade da asma basearam-se nas recomendações do Global Initiative for Asthma. Pacientes menores de 11 anos receberam fluticasona na dose de 200 mcg/dia, e aqueles com mais de 11 anos receberam 300 mcg/dia. Após 10 semanas de tratamento, a dosagem do cortisol foi realizada para avaliação da função adrenal. RESULTADOS: Foram avaliados 41 pacientes (65,9 por cento do sexo masculino) entre 6 e 18 anos. Não houve diferença significativa entre as médias de cortisol basal nos pacientes que receberam 200 mcg/dia de propionato de fluticasona (n = 13) e naqueles que receberam 300 mcg/dia (n = 28). CONCLUSÕES: Os achados mostram que doses baixas a moderadas de propionato de fluticasona não causam supressão adrenal.

OBJECTIVES: To evaluate basal plasma cortisol in persistent asthmatics on inhaled fluticasone propionate 200 mcg/day and 300 mcg/day. METHODS: Asthma diagnosis and classification was based on Global Initiative for Asthma recommendations. Patients aged 11 years old or less received fluticasone propionate 200 mcg/day and those older than 11 years received 300 mcg/day. After 10 weeks of treatment, plasma cortisol levels were monitored to evaluate the hypothalamic-pituitary-adrenal axis. RESULTS: Forty-one patients (65.9 percent males) aged 6 to 18 years old were evaluated. No statistical differences were found between plasma cortisol levels in patients who received 200 mcg/day (n = 13) and those who received 300 mcg/day (n = 28). CONCLUSIONS: Our results show that low and moderate doses of fluticasone propionate do not cause adrenal suppression.

Determinação das concentrações plasmáticas de salbutamol pós-nebulização em serviço de emergência pediátrica / Determination of plasma salbutamol concentrations after nebulization in a pediatric emergency department

OBJETIVOS: Validar parcialmente a metodologia para determinação do salbutamol em plasma humano por cromatografia líquida de alta eficiência (detecção por fluorescência). Analisar as concentrações plasmáticas de salbutamol em um grupo de pacientes pediátricos com indicação de nebulizações em sala de emergência. MÉTODO: Estudo transversal, analítico, prospectivo, do tipo série de casos. Foram selecionados consecutivamente 15 pacientes com idade entre 12 e 37meses, com diagnóstico de crise aguda de asma, atendidos no Serviço de Emergência Pediátrica do Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Os pacientes foram tratados conforme a rotina da unidade para manejo de crise aguda de asma: nebulização (fluxo 6-8 L/min) com salbutamol (0,15 mg/kg) diluídosem4mL de NaCL 0,9 por cento. A nebulização era administrada seqüencialmente, em intervalos de 20 minutos, por três vezes. Concomitantemente às nebulizações, todos os pacientes recebiam prednisolona via oral (1 mg/kg). RESULTADOS: As concentrações plasmáticas evidenciaram grande variabilidade em portadores de crise aguda de asma que receberam três nebulizações com salbutamol (0,15 mg/kg). Níveis plasmáticos médios foram de 12,09±10,8 ng/mL, com mediana de 8,9 (IQ25-75 por cento 2,75-17,65) e coeficiente de variação da amostra de 92,4 por cento. CONCLUSÕES: As concentrações plasmáticas após inalação de salbutamol apresentam grande dispersão na população pediátrica, a exemplo de outros estudos. As possíveis causas e implicações relacionadas ao achado permanecem alvo de controvérsias e avaliações complementares.

OBJECTIVES: To partially validate the methodology for determining salbutamol in human plasma through high-efficiency liquid chromatography and fluorescence detection. To analyze plasma salbutamol concentrations in a group of pediatric patients with indication for nebulization in the emergency room. METHOD: Analytical, prospective cross-sectional case series. Fifteen patients aged 12 to 37 months with a diagnosis of acute asthma crisis were selected at the Pediatric Emergency Service at Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brazil. The patients were treated following the unit's routine for the management of acute asthma crises: nebulization with salbutamol (flow rate of 6-8 L/min) (0.15 mg/kg) suspended in 4 mL of 0.9 percent saline solution. Nebulization was administered sequentially, three times, at 20 minute intervals. All patients were given prednisolone orally (1 mg/kg) concurrently with the nebulizations. RESULTS: Plasma concentrations exhibited great variability in acute asthma crisis patients given three nebulizations of salbutamol (0.15 mg/kg). The mean level in plasma was 12.09 ± 10.8 ng/mL, with a median of 8.9 ng/mL (IQ25-75 percent 2.75-17.65). The sample's coefficient of variation was 92.4 percent. CONCLUSIONS: Post-inhalation plasma salbutamol concentrations exhibit great variation in the pediatric population, as seen in other studies. The possible causes and implications of this finding remain the subject of disagreements and of further assessments.

Total IgE level in respiratory allergy: study of patients at high risk for helminthic infection

OBJETIVO: Eosinofilia e elevação de IgE sérica são expressões de atopia, contudo há fatores intervenientes como, por exemplo, as parasitoses intestinais. Esta pesquisa verifica a relação entre IgE sérica total, eosinófilos e IgE específica anti-áscaris em indivíduos portadores de asma e/ou rinite alérgica. MÉTODOS: Estudo do tipo transversal em adolescentes portadores de asma e/ou rinite alérgica que foram examinados quanto ao nível sérico de IgE total, de IgE anti-áscaris e de contagem dos eosinófilos sangüíneos. RESULTADOS: Foram analisados 101 pacientes com idade entre 12 e 21 anos. A mediana da IgE foi 660 UI/mL (P25-75 243,5-1500), e a dos eosinófilos foi 510 células/mm³ (P25-75 284-811). A IgE anti-áscaris foi positiva em 73 por cento (74/101) da amostra, mas houve apenas 33,7 por cento (34/101) de positividade ao parasitológico de fezes. Os coeficientes de correlação encontrados foram: 0,34 (p = 0,001) entre IgE total e eosinófilos, 0,52 (p < 0,001) entre IgE total e IgE anti-áscaris e 0,26 (p = 0,01) entre eosinófilos e IgE anti-áscaris. O modelo de regressão linear múltipla final encontrou que IgE anti-áscaris foi fator contribuinte para IgE sérica total com coeficiente de determinação (r2 ajustado) de 0,25 (F = 12,35; p < 0,001), e esse efeito foi independente de contagem de eosinófilos séricos e de parasitose intestinal por helmintos. CONCLUSÃO: Em pacientes com alergia respiratória e IgE sérica total bastante elevada, oriundos de áreas com alto risco de infecção por helmintos, a pesquisa de IgE anti-áscaris como possível fator explicativo pode ser de maior ajuda que a realização do parasitológico de fezes.

OBJECTIVE: Eosinophilia and increased serum IgE levels are indicators of atopy; however, other factors can also play a key role, such as intestinal parasitic infections. This study assesses the relationship between total serum IgE, eosinophil count, and anti-Ascaris IgE in individuals with asthma and/or allergic rhinitis. METHODS: A cross-sectional study was carried out in adolescents with asthma and/or allergic rhinitis. The patients had their total serum IgE, anti-Ascaris IgE and eosinophil count measured. RESULTS: A total of 101 patients aged 12 to 21 years were assessed. Median IgE level was 660 IU/mL (P25-75 243.5-1500), and the eosinophil count corresponded to 510 cells/mm³ (P25-75 284-811). Anti-Ascaris IgE was positive in 73 percent (74/101) of the individuals, but parasitological stool examination yielded positive results in only 33.7 percent (34/101). The correlation coefficients were the following: 0.34 (p = 0.001) between total IgE level and eosinophil count, 0.52 (p < 0.001) between total IgE level and anti-Ascaris IgE, and 0.26 (p = 0.01) between eosinophil count and anti-Ascaris IgE. The final multiple linear regression model pointed out that anti-Ascaris IgE contributed to a total serum IgE level with a coefficient of determination (adjusted R²) of 0.25 (F = 12.35; p < 0.001). This effect occurred regardless of eosinophil count and of the presence of intestinal helminthic infection. CONCLUSION: In patients with respiratory allergy and increased total serum IgE levels living in areas where there is a high risk for helminthic infections, the quantification of anti-Ascaris IgE can be more useful and more insightful than the parasitological stool examination.

Alfa 1 antitrypsin and protease levels in Puerto Rican asthmatics: a pilot study

A cross-sectional pilot study was conducted on a population of 119 asthmatics who had been recruited from the Emergency Room Department of a major hospital in Ponce, Puerto Rico. The purpose of the study was to determine the frequency of the MM, MS, and SS a-i-antiprotease variants. Also, we analyzed the serum levels of the alpha-1-antiprotease inhibitor, quantified the levels of serine proteases in homes of the asthmatic volunteers, and determined whether environmental levels of proteases, regardless of their sources, had any association with either asthma symptoms or alpha-1-antiprotease inhibitor phenotypes. Our results do not support the role of the alpha-1-antiprotease as a risk factor for asthma in the study population as previously reported. Patients who had visited the ED due to asthma on 3 or more occasions had significantly higher trypsin levels than those who had done so 2 or fewer times. Of those asthmatic patients who had daily symptoms, 40had been exposed to high levels of elastase, and 33.3to trypsin. Similarly, 52.9of the patients with 2 or more hospitalizations a year had been exposed to high elastase levels, and 40.5of asthma patients who had nocturnal asthma more than 3 times a week had been exposed to high levels of elastase.

Diagnóstico de alergia a baratas no ambiente clínico: estudo comparativo entre o teste cutâneo e IgE específica / Use of the skin prick test and specific immunoglobulin E for the diagnosis of cockroach allergy

OBJETIVOS: Comparar a prevalência da sensibilização a baratas (Blattella germanica e Periplaneta americana) em crianças com e sem asma, verificando a concordância entre testes cutâneos e IgE específica bem como determinar a relação entre a sensibilização a baratas e níveis séricos de IgE total. MÉTODOS: Foi realizado um estudo caso-controle, envolvendo 76 crianças asmáticas e 42 não asmáticas, entre 6 e 14 anos de idade, em Recife, Brasil. Todas as crianças submeteram-se ao teste cutâneo e dosagem sérica de IgE específica para B. germanica e P. americana e determinação sérica da IgE total. RESULTADOS: As crianças asmáticas apresentaram maior positividade aos testes cutâneos para B. germanica (27,6 versus 4,8 por cento) e P. americana (27,6 versus 2,4 por cento) que aquelas do grupo controle. A concordância entre o teste cutâneo e a IgE específica foi razoável para B. germanica (Kappa = 0,25) e fraca para P. americana (Kappa = 0,17). A média geométrica da IgE total foi 591,70 kU/L entre pacientes asmáticos e 345,85 kU/L entre os controles, não havendo diferença estatisticamente significante. Em pacientes com testes positivos para baratas, a média geométrica da IgE total foi significativamente maior em comparação aos pacientes cujos exames foram negativos. CONCLUSÃO: A sensibilização a baratas foi associada à asma. O teste cutâneo pode refletir mais apropriadamente uma sensibilização a baratas clinicamente relevante que a IgE específica.

Immunoblot analysis and comparative IgE responses of atopic patients to extracts of the domestic mite Blomia tropicalis

BACKGROUND: The domestic mite Blomia tropicalis is found in subtropical and tropical environments, and its clinical importance as a sensitizing agent in allergic disease is widely accepted. OBJECTIVE: To investigate the IgE reactivity to allergens present in extracts of the domestic mite B. tropicalis, and compare the IgE responses to these allergens by asthmatics, patients with atopic dermatitis and allergic rhinitis, as well as nonatopic controls. METHODS: Extracts from B. tropicalis were used for skin tests. The B. tropicalis specific IgE in the serum were measured using the FAST Plus Test and immunoblot analysis. RESULTS: A total of 199 volunteers participated in the study. The data show that 18 out of 29 polypeptide bands present in extracts of this mite species were recognized by the allergic and control sera. Of these allergens, four showed a high IgE binding frequency and had relative molecular weights of 104, 80, 68 and 14 kDa. The 14 kDa allergen demonstrated the highest IgE binding frequency. CONCLUSION: Sera from atopic patients reacted to more allergens than sera from patients controls. Extracts from pure bodies of B. tropicalis contain one immunodominant and three important allergens. A common characteristic between all of the sera tested was the high degree of serum IgE reactivity observed to the 14 kDa allergen.

Efecto de dosis altas de budesonida y función suprarrenal de niños asmáticos severos / High doses of inhaled budesonide and adrenal function in children with severe asthma

Background: The use of inhaled steroids is common in the treatment of bronchial asthma in children. Aim: To assess adrenocortical function in children with severe asthma receiving inhaled budesonide for six or more months. Material and methods: Children with severe asthma that required 800 µg/day or more of inhaled budesonide and that did not required systemic steroids for more than six days in the last four months to control their disease, were studied. Serum cortisol was measured one hour after administration of 0.25 mg of ACTH (Cosyntropin®) intravenously. The test was considered normal if post stimulation serum cortisol was over 18 µg/ml. Results: Twenty children (aged 5 to 14 years, 15 males), were studied. The stimulation test was normal in 17 children. Conclusions: Alterations in adrenal function are present in a small proportion of asthmatic children who require 800 µg/day of inhaled budesonide.

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 ± 6.24 percent) in sputum whereas neutrophils (63.3 ± 4.66 percent) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 ± 330.7 pg/ml) and plasma (716.6 ± 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 ± 105.2 pg/ml) and TNF-alpha (308.8 ± 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 ± 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma

Asthma is an inflammatory condition characterized by the involvement of several mediators, including reactive oxygen species. The aim of the present study was to investigate the superoxide release and cellular glutathione peroxidase (cGPx) activity in peripheral blood granulocytes and monocytes from children and adolescents with atopic asthma. Forty-four patients were selected and classified as having intermittent or persistent asthma (mild, moderate or severe). The spontaneous or phorbol myristate acetate (PMA, 30 nM)-induced superoxide release by granulocytes and monocytes was determined at 0, 5, 15, and 25 min. cGPx activity was assayed spectrophotometrically. The spontaneous superoxide release by granulocytes from patients with mild (N = 15), moderate (N = 12) or severe (N = 6) asthma was higher at 25 min compared to healthy individuals (N = 28, P < 0.05, Duncan test). The PMA-induced superoxide release by granulocytes from patients with moderate (N = 12) or severe (N = 6) asthma was higher at 15 and 25 min compared to healthy individuals (N = 28, P < 0.05 in both times of incubation, Duncan test). The spontaneous or PMA-induced superoxide release by monocytes from asthmatic patients was similar to healthy individuals (P > 0.05 in all times of incubation, Duncan test). cGPx activity of granulocytes and monocytes from patients with persistent asthma (N = 20) was also similar to healthy individuals (N = 10, P > 0.05, Kruskal-Wallis test). We conclude that, under specific circumstances, granulocytes from children with persistent asthma present a higher respiratory burst activity compared to healthy individuals. These findings indicate a risk of oxidative stress, phagocyte auto-oxidation, and the subsequent release of intracellular toxic oxidants and enzymes, leading to additional inflammation and lung damage in asthmatic children.